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ESP: PubMed Auto Bibliography 09 Mar 2025 at 01:33 Created:
Origin of Multicellular Eukaryotes
Created with PubMed® Query: ( (origin OR evolution) AND (eukaryotes OR eukaryota) AND (multicelluarity OR multicellular) NOT 33634751[PMID] ) NOT pmcbook NOT ispreviousversion
Citations The Papers (from PubMed®)
RevDate: 2025-03-05
Genome duplication in a long-term multicellularity evolution experiment.
Nature [Epub ahead of print].
Whole-genome duplication (WGD) is widespread across eukaryotes and can promote adaptive evolution[1-4]. However, given the instability of newly formed polyploid genomes[5-7], understanding how WGDs arise in a population, persist, and underpin adaptations remains a challenge. Here, using our ongoing Multicellularity Long Term Evolution Experiment (MuLTEE)[8], we show that diploid snowflake yeast (Saccharomyces cerevisiae) under selection for larger multicellular size rapidly evolve to be tetraploid. From their origin within the first 50 days of the experiment, tetraploids persisted for the next 950 days (nearly 5,000 generations, the current leading edge of our experiment) in 10 replicate populations, despite being genomically unstable. Using synthetic reconstruction, biophysical modelling and counter-selection, we found that tetraploidy evolved because it confers immediate fitness benefits under this selection, by producing larger, longer cells that yield larger clusters. The same selective benefit also maintained tetraploidy over long evolutionary timescales, inhibiting the reversion to diploidy that is typically seen in laboratory evolution experiments. Once established, tetraploidy facilitated novel genetic routes for adaptation, having a key role in the evolution of macroscopic multicellular size via the origin of evolutionarily conserved aneuploidy. These results provide unique empirical insights into the evolutionary dynamics and impacts of WGD, showing how it can initially arise due to its immediate adaptive benefits, be maintained by selection and fuel long-term innovations by creating additional dimensions of heritable genetic variation.
Additional Links: PMID-40044858
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@article {pmid40044858,
year = {2025},
author = {Tong, K and Datta, S and Cheng, V and Haas, DJ and Gourisetti, S and Yopp, HL and Day, TC and Lac, DT and Khalil, AS and Conlin, PL and Bozdag, GO and Ratcliff, WC},
title = {Genome duplication in a long-term multicellularity evolution experiment.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40044858},
issn = {1476-4687},
abstract = {Whole-genome duplication (WGD) is widespread across eukaryotes and can promote adaptive evolution[1-4]. However, given the instability of newly formed polyploid genomes[5-7], understanding how WGDs arise in a population, persist, and underpin adaptations remains a challenge. Here, using our ongoing Multicellularity Long Term Evolution Experiment (MuLTEE)[8], we show that diploid snowflake yeast (Saccharomyces cerevisiae) under selection for larger multicellular size rapidly evolve to be tetraploid. From their origin within the first 50 days of the experiment, tetraploids persisted for the next 950 days (nearly 5,000 generations, the current leading edge of our experiment) in 10 replicate populations, despite being genomically unstable. Using synthetic reconstruction, biophysical modelling and counter-selection, we found that tetraploidy evolved because it confers immediate fitness benefits under this selection, by producing larger, longer cells that yield larger clusters. The same selective benefit also maintained tetraploidy over long evolutionary timescales, inhibiting the reversion to diploidy that is typically seen in laboratory evolution experiments. Once established, tetraploidy facilitated novel genetic routes for adaptation, having a key role in the evolution of macroscopic multicellular size via the origin of evolutionarily conserved aneuploidy. These results provide unique empirical insights into the evolutionary dynamics and impacts of WGD, showing how it can initially arise due to its immediate adaptive benefits, be maintained by selection and fuel long-term innovations by creating additional dimensions of heritable genetic variation.},
}
RevDate: 2025-03-06
CmpDate: 2025-03-05
Evolution of irreversible differentiation under stage-dependent cell differentiation.
Scientific reports, 15(1):7786.
The specialization of cells is a hallmark of complex multicellularity. Cell differentiation enables the emergence of specialized cell types that carry out separate functions previously executed by a multifunctional ancestor cell. One view about the origin of cell differentiation is that it first occurred randomly in genetically identical cells exposed to the same life history environment. Under these conditions, differentiation trajectories producing more offspring could be favored by natural selection; yet, how dynamic variation in differentiation probabilities can affect the evolution of differentiation patterns is unclear. We develop a theoretical model to investigate the effect of dynamic-stage-dependent-cell differentiation on the evolution of optimal differentiation patterns. Concretely, we model trajectories in which cells can randomly differentiate into germ or soma cell types at each cell division. After comparing many of these trajectories, we found that irreversible differentiation, where cells gradually lose their ability to produce the other cell type, is more favored in small organisms under dynamic than under constant (stage-independent) cell differentiation. Furthermore, we found that the irreversible differentiation of germ cells, where germ cells gradually lose their ability to produce soma cells, is prominent among irreversible patterns. Only large variations in the differentiation probabilities prohibit irreversible trajectories from being the optimal pattern.
Additional Links: PMID-40044726
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@article {pmid40044726,
year = {2025},
author = {Gao, Y and Pichugin, Y and Traulsen, A and Zapién-Campos, R},
title = {Evolution of irreversible differentiation under stage-dependent cell differentiation.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {7786},
pmid = {40044726},
issn = {2045-2322},
support = {12401644//National Natural Science Foundation of China/ ; 2024JC-YBQN-0005//Natural Science Basic Research Program of Shaanxi Province/ ; },
mesh = {*Cell Differentiation ; *Biological Evolution ; Germ Cells/cytology ; Models, Biological ; Animals ; Cell Division ; Selection, Genetic ; },
abstract = {The specialization of cells is a hallmark of complex multicellularity. Cell differentiation enables the emergence of specialized cell types that carry out separate functions previously executed by a multifunctional ancestor cell. One view about the origin of cell differentiation is that it first occurred randomly in genetically identical cells exposed to the same life history environment. Under these conditions, differentiation trajectories producing more offspring could be favored by natural selection; yet, how dynamic variation in differentiation probabilities can affect the evolution of differentiation patterns is unclear. We develop a theoretical model to investigate the effect of dynamic-stage-dependent-cell differentiation on the evolution of optimal differentiation patterns. Concretely, we model trajectories in which cells can randomly differentiate into germ or soma cell types at each cell division. After comparing many of these trajectories, we found that irreversible differentiation, where cells gradually lose their ability to produce the other cell type, is more favored in small organisms under dynamic than under constant (stage-independent) cell differentiation. Furthermore, we found that the irreversible differentiation of germ cells, where germ cells gradually lose their ability to produce soma cells, is prominent among irreversible patterns. Only large variations in the differentiation probabilities prohibit irreversible trajectories from being the optimal pattern.},
}
MeSH Terms:
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*Cell Differentiation
*Biological Evolution
Germ Cells/cytology
Models, Biological
Animals
Cell Division
Selection, Genetic
RevDate: 2025-03-06
CmpDate: 2025-03-06
Glycerol improves the viability of a cryopreserved choanoflagellate.
Cryobiology, 118:105183.
The colonial choanoflagellate Salpingoeca rosetta is a tractable model system for studying the origins of multicellularity, but long-term storage strategies for this species have not been tested. In this study, we probed each stage of cryopreservation (cooling, long-term storage, recovery) to identify the optimal protocol for recovery of S. rosetta and co-cultured bacterial cells. Dimethyl sulfoxide (Me2SO; commonly referred to as DMSO), the current cryoprotective agent (CPA) standard, proved to be worse than glycerol at comparable concentrations. Samples treated with either CPA at 5 % showed the poorest recovery. Our results identified 15 % glycerol as the most effective CPA for both S. rosetta and Echinicola pacifica. We also determined that ultra-low temperature freezers can be sufficient for short-term storage. We propose 15 % glycerol and liquid phase nitrogen as the standard cryopreservation protocol for S. rosetta cultures and as a starting point for testing long-term storage strategies for other choanoflagellates and heterotrophic protists.
Additional Links: PMID-39617193
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@article {pmid39617193,
year = {2025},
author = {Chandra, S and Rutaganira, FU},
title = {Glycerol improves the viability of a cryopreserved choanoflagellate.},
journal = {Cryobiology},
volume = {118},
number = {},
pages = {105183},
doi = {10.1016/j.cryobiol.2024.105183},
pmid = {39617193},
issn = {1090-2392},
mesh = {*Glycerol/pharmacology ; *Cryopreservation/methods ; *Cryoprotective Agents/pharmacology ; *Choanoflagellata/drug effects ; *Dimethyl Sulfoxide/pharmacology ; Cell Survival/drug effects ; },
abstract = {The colonial choanoflagellate Salpingoeca rosetta is a tractable model system for studying the origins of multicellularity, but long-term storage strategies for this species have not been tested. In this study, we probed each stage of cryopreservation (cooling, long-term storage, recovery) to identify the optimal protocol for recovery of S. rosetta and co-cultured bacterial cells. Dimethyl sulfoxide (Me2SO; commonly referred to as DMSO), the current cryoprotective agent (CPA) standard, proved to be worse than glycerol at comparable concentrations. Samples treated with either CPA at 5 % showed the poorest recovery. Our results identified 15 % glycerol as the most effective CPA for both S. rosetta and Echinicola pacifica. We also determined that ultra-low temperature freezers can be sufficient for short-term storage. We propose 15 % glycerol and liquid phase nitrogen as the standard cryopreservation protocol for S. rosetta cultures and as a starting point for testing long-term storage strategies for other choanoflagellates and heterotrophic protists.},
}
MeSH Terms:
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*Glycerol/pharmacology
*Cryopreservation/methods
*Cryoprotective Agents/pharmacology
*Choanoflagellata/drug effects
*Dimethyl Sulfoxide/pharmacology
Cell Survival/drug effects
RevDate: 2025-03-05
CmpDate: 2025-03-05
Knowledge of microalgal Rubiscos helps to improve photosynthetic efficiency of crops.
Planta, 261(4):78.
A comprehensive understanding of microalgal Rubiscos offers opportunities to enhance photosynthetic efficiency of crops. As food production fails to meet the needs of the expanding population, there is increasing concern about Ribulose-1, 5-diphosphate (RuBP) carboxylase/oxygenase (Rubisco), the enzyme that catalyzes CO2 fixation in photosynthesis. There have been many attempts to optimize Rubisco in crops, but the complex multicellular structure of higher plants makes optimization more difficult. Microalgae have the characteristics of rapid growth, simple structure and easy molecular modification, and the function and properties of their Rubiscos are basically the same as those of higher plants. Research on microalgal Rubiscos helps to broaden the understanding of Rubiscos of higher plants. Also, transferring all or part of better microalgal Rubiscos into crop cells or giving crop Rubiscos the advantages of microalgal Rubiscos can help improve the photosynthesis of crops. In this review, the distribution, origin, evolution, molecular structure, folding, assembly, activation and kinetic properties of microalgal Rubiscos are summarized. Moreover, the development of some effective methods to improve the properties and application of Rubiscos in microalgae are also described.
Additional Links: PMID-40042639
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@article {pmid40042639,
year = {2025},
author = {Zhu, T and Ning, P and Liu, Y and Liu, M and Yang, J and Wang, Z and Li, M},
title = {Knowledge of microalgal Rubiscos helps to improve photosynthetic efficiency of crops.},
journal = {Planta},
volume = {261},
number = {4},
pages = {78},
pmid = {40042639},
issn = {1432-2048},
support = {6651121004//"First class grass land science discipline" program in Shandong Province, the Talents of High Level Scientific Research Foundation of Qingdao Agricultural University/ ; 6651120032//"First class grass land science discipline" program in Shandong Province, the Talents of High Level Scientific Research Foundation of Qingdao Agricultural University/ ; 22278233//National Natural Science Foundation of China/ ; ZR2022QB143//Natural Science Foundation of Shandong Province/ ; ZR2020QC069//Natural Science Foundation of Shandong Province/ ; M2023-05//State Key Laboratory of Microbial Resources, Chinese Academy of Sciences/ ; M2022-07//State Key Laboratory of Microbial Technology Open Projects Fund/ ; },
mesh = {*Microalgae/physiology/metabolism ; *Crops, Agricultural/metabolism/physiology ; *Photosynthesis/physiology ; *Ribulose-Bisphosphate Carboxylase/metabolism ; },
abstract = {A comprehensive understanding of microalgal Rubiscos offers opportunities to enhance photosynthetic efficiency of crops. As food production fails to meet the needs of the expanding population, there is increasing concern about Ribulose-1, 5-diphosphate (RuBP) carboxylase/oxygenase (Rubisco), the enzyme that catalyzes CO2 fixation in photosynthesis. There have been many attempts to optimize Rubisco in crops, but the complex multicellular structure of higher plants makes optimization more difficult. Microalgae have the characteristics of rapid growth, simple structure and easy molecular modification, and the function and properties of their Rubiscos are basically the same as those of higher plants. Research on microalgal Rubiscos helps to broaden the understanding of Rubiscos of higher plants. Also, transferring all or part of better microalgal Rubiscos into crop cells or giving crop Rubiscos the advantages of microalgal Rubiscos can help improve the photosynthesis of crops. In this review, the distribution, origin, evolution, molecular structure, folding, assembly, activation and kinetic properties of microalgal Rubiscos are summarized. Moreover, the development of some effective methods to improve the properties and application of Rubiscos in microalgae are also described.},
}
MeSH Terms:
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*Microalgae/physiology/metabolism
*Crops, Agricultural/metabolism/physiology
*Photosynthesis/physiology
*Ribulose-Bisphosphate Carboxylase/metabolism
RevDate: 2025-02-27
CmpDate: 2025-02-27
Principles of long-range gene regulation.
Current opinion in genetics & development, 91:102323.
Transcription from gene promoters occurs in specific spatiotemporal patterns in multicellular organisms, controlled by genomic regulatory elements. The communication between a regulatory element and a promoter requires a certain degree of physical proximity between them; hence, most gene regulation occurs locally in the genome. However, recent discoveries have revealed long-range gene regulation strategies that enhance interactions between regulatory elements and promoters by overcoming the distances between them in the linear genome. These new findings challenge the traditional view of how gene expression patterns are controlled. This review examines long-range gene regulation strategies recently reported in Drosophila and mammals, offering insights into their mechanisms and evolution.
Additional Links: PMID-39947017
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PubMed:
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@article {pmid39947017,
year = {2025},
author = {Zunjarrao, S and Gambetta, MC},
title = {Principles of long-range gene regulation.},
journal = {Current opinion in genetics & development},
volume = {91},
number = {},
pages = {102323},
doi = {10.1016/j.gde.2025.102323},
pmid = {39947017},
issn = {1879-0380},
mesh = {Animals ; *Gene Expression Regulation/genetics ; *Promoter Regions, Genetic ; Drosophila/genetics ; Genome/genetics ; Humans ; Transcription, Genetic ; Mammals/genetics ; Evolution, Molecular ; },
abstract = {Transcription from gene promoters occurs in specific spatiotemporal patterns in multicellular organisms, controlled by genomic regulatory elements. The communication between a regulatory element and a promoter requires a certain degree of physical proximity between them; hence, most gene regulation occurs locally in the genome. However, recent discoveries have revealed long-range gene regulation strategies that enhance interactions between regulatory elements and promoters by overcoming the distances between them in the linear genome. These new findings challenge the traditional view of how gene expression patterns are controlled. This review examines long-range gene regulation strategies recently reported in Drosophila and mammals, offering insights into their mechanisms and evolution.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Gene Expression Regulation/genetics
*Promoter Regions, Genetic
Drosophila/genetics
Genome/genetics
Humans
Transcription, Genetic
Mammals/genetics
Evolution, Molecular
RevDate: 2025-02-26
Cell differentiation controls iron assimilation in the choanoflagellate Salpingoeca rosetta.
mSphere [Epub ahead of print].
UNLABELLED: Marine microeukaryotes have evolved diverse cellular features that link their life histories to surrounding environments. How those dynamic life histories intersect with the ecological functions of microeukaryotes remains a frontier to understanding their roles in critical biogeochemical cycles. Choanoflagellates, phagotrophs that cycle nutrients through filter feeding, provide models to explore this intersection, for many choanoflagellate species transition between life history stages by differentiating into distinct cell types. Here, we report that cell differentiation in the marine choanoflagellate Salpingoeca rosetta endows one of its cell types with the ability to utilize insoluble ferric colloids. These colloids are a predominant form of iron in marine environments and are largely inaccessible to cell-walled microbes. Therefore, choanoflagellates and other phagotrophic eukaryotes may serve critical ecological roles by cycling this essential nutrient through iron utilization pathways. We found that S. rosetta can utilize these ferric colloids via the expression of a cytochrome b561 iron reductase (cytb561a). This gene and its mammalian ortholog, the duodenal cytochrome b561 (DCYTB) that reduces ferric cations for uptake in gut epithelia, belong to a subgroup of cytochrome b561 proteins with distinct biochemical features that contribute to iron reduction activity. Overall, our findings provide insight into the ecological roles choanoflagellates perform and inform reconstructions of early animal evolution where functionally distinct cell types became an integrated whole at the origin of animal multicellularity.
IMPORTANCE: This study examines how cell differentiation in a choanoflagellate enables the uptake of iron, an essential nutrient. Choanoflagellates are widespread, aquatic microeukaryotes that are the closest living relatives of animals. Similar to their animal relatives, we found that the model choanoflagellate, S. rosetta, divides metabolic functions between distinct cell types. One cell type uses an iron reductase to acquire ferric colloids, a key source of iron in the ocean. We also observed that S. rosetta has three variants of this reductase, each with distinct biochemical properties that likely lead to differences in how they reduce iron. These reductases are variably distributed across ocean regions, suggesting a role for choanoflagellates in cycling iron in marine environments.
Additional Links: PMID-40008892
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PubMed:
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@article {pmid40008892,
year = {2025},
author = {Leon, F and Espinoza-Esparza, JM and Deng, V and Coyle, MC and Espinoza, S and Booth, DS},
title = {Cell differentiation controls iron assimilation in the choanoflagellate Salpingoeca rosetta.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0091724},
doi = {10.1128/msphere.00917-24},
pmid = {40008892},
issn = {2379-5042},
abstract = {UNLABELLED: Marine microeukaryotes have evolved diverse cellular features that link their life histories to surrounding environments. How those dynamic life histories intersect with the ecological functions of microeukaryotes remains a frontier to understanding their roles in critical biogeochemical cycles. Choanoflagellates, phagotrophs that cycle nutrients through filter feeding, provide models to explore this intersection, for many choanoflagellate species transition between life history stages by differentiating into distinct cell types. Here, we report that cell differentiation in the marine choanoflagellate Salpingoeca rosetta endows one of its cell types with the ability to utilize insoluble ferric colloids. These colloids are a predominant form of iron in marine environments and are largely inaccessible to cell-walled microbes. Therefore, choanoflagellates and other phagotrophic eukaryotes may serve critical ecological roles by cycling this essential nutrient through iron utilization pathways. We found that S. rosetta can utilize these ferric colloids via the expression of a cytochrome b561 iron reductase (cytb561a). This gene and its mammalian ortholog, the duodenal cytochrome b561 (DCYTB) that reduces ferric cations for uptake in gut epithelia, belong to a subgroup of cytochrome b561 proteins with distinct biochemical features that contribute to iron reduction activity. Overall, our findings provide insight into the ecological roles choanoflagellates perform and inform reconstructions of early animal evolution where functionally distinct cell types became an integrated whole at the origin of animal multicellularity.
IMPORTANCE: This study examines how cell differentiation in a choanoflagellate enables the uptake of iron, an essential nutrient. Choanoflagellates are widespread, aquatic microeukaryotes that are the closest living relatives of animals. Similar to their animal relatives, we found that the model choanoflagellate, S. rosetta, divides metabolic functions between distinct cell types. One cell type uses an iron reductase to acquire ferric colloids, a key source of iron in the ocean. We also observed that S. rosetta has three variants of this reductase, each with distinct biochemical properties that likely lead to differences in how they reduce iron. These reductases are variably distributed across ocean regions, suggesting a role for choanoflagellates in cycling iron in marine environments.},
}
RevDate: 2025-02-25
CmpDate: 2025-02-25
Innovation in ant larval feeding facilitated queen-worker divergence and social complexity.
Proceedings of the National Academy of Sciences of the United States of America, 122(9):e2413742122.
Building differences between genetically equivalent units is a fundamental challenge for all multicellular organisms and superorganisms. In ants, reproductive or worker fate is typically determined during the larval stage, through feeding regimes managed by adult caretakers. However, the feeding care provided to larvae varies significantly across ants, as does phenotypic divergence between queen and worker castes. Here, we employed comparative phylogenetic methods and causal inference to investigate the relationships between larval feeding care, caste size dimorphism, and social complexity across ant diversity. We digitized the life's work of George and Jeanette Wheeler, cataloging the larval morphology of over 700 species, and we compiled data on species diets and larval feeding behaviors from the literature and our own observations. We measured queen-worker size dimorphism in 392 species and gathered data for colony size, worker polymorphism, and worker reproduction. Our analyses revealed that ancestral active-feeding larvae evolved passive morphologies when adults began feeding them individually, typically with processed material and often following a shift to nonpredatory diets. Greater queen-worker size dimorphism coevolved with larval passiveness, alongside traits indicative of increased social complexity, including larger colony sizes, worker subcastes, and a reduction in workers' reproductive potential. Likelihood comparisons of causal phylogenetic models support that extended alloparental care facilitated stronger caste dimorphism, which, in turn and along with increased colony sizes, promoted higher social complexity. Our results suggest that enhanced adult control over larval development enabled greater phenotypic specialization within colonies, with profound implications for social evolution.
Additional Links: PMID-39999174
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PubMed:
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@article {pmid39999174,
year = {2025},
author = {Matte, A and LeBoeuf, AC},
title = {Innovation in ant larval feeding facilitated queen-worker divergence and social complexity.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {9},
pages = {e2413742122},
doi = {10.1073/pnas.2413742122},
pmid = {39999174},
issn = {1091-6490},
support = {PR00P3_179776//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)/ ; },
mesh = {Animals ; *Ants/physiology ; *Larva/physiology/growth & development ; *Feeding Behavior/physiology ; *Social Behavior ; Phylogeny ; Biological Evolution ; Female ; Reproduction/physiology ; Behavior, Animal/physiology ; },
abstract = {Building differences between genetically equivalent units is a fundamental challenge for all multicellular organisms and superorganisms. In ants, reproductive or worker fate is typically determined during the larval stage, through feeding regimes managed by adult caretakers. However, the feeding care provided to larvae varies significantly across ants, as does phenotypic divergence between queen and worker castes. Here, we employed comparative phylogenetic methods and causal inference to investigate the relationships between larval feeding care, caste size dimorphism, and social complexity across ant diversity. We digitized the life's work of George and Jeanette Wheeler, cataloging the larval morphology of over 700 species, and we compiled data on species diets and larval feeding behaviors from the literature and our own observations. We measured queen-worker size dimorphism in 392 species and gathered data for colony size, worker polymorphism, and worker reproduction. Our analyses revealed that ancestral active-feeding larvae evolved passive morphologies when adults began feeding them individually, typically with processed material and often following a shift to nonpredatory diets. Greater queen-worker size dimorphism coevolved with larval passiveness, alongside traits indicative of increased social complexity, including larger colony sizes, worker subcastes, and a reduction in workers' reproductive potential. Likelihood comparisons of causal phylogenetic models support that extended alloparental care facilitated stronger caste dimorphism, which, in turn and along with increased colony sizes, promoted higher social complexity. Our results suggest that enhanced adult control over larval development enabled greater phenotypic specialization within colonies, with profound implications for social evolution.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Ants/physiology
*Larva/physiology/growth & development
*Feeding Behavior/physiology
*Social Behavior
Phylogeny
Biological Evolution
Female
Reproduction/physiology
Behavior, Animal/physiology
RevDate: 2025-02-25
CmpDate: 2025-02-25
Male secreted short glycoproteins link sperm competition to the reproductive isolation of species.
Current biology : CB, 35(4):911-917.e5.
Sperm competition is found across multicellular organisms[1][,][2][,][3][,][4] using both external and internal fertilization.[5][,][6] Sperm competition and post-copulatory cryptic female choice can promote incompatibility between species due to the antagonistic coevolution of the sexes within a species.[7][,][8][,][9][,][10][,][11] This between-species incompatibility is accelerated and markedly asymmetrical when sexual mode differs, producing the "weak inbreeder, strong outcrosser" (WISO) pattern.[12] Here, we show that male secreted short (MSS) sperm glycoproteins of nematodes constitute a gametic effector of WISO. In obligately outcrossing Caenorhabditis, MSS is dispensable for baseline fertility but required for intraspecific sperm competitiveness.[13] MSS is lost in self-fertile lineages, likely as a response to selection for a hermaphrodite-biased sex ratio.[14] Selfing hermaphrodites that mate with males of closely related outcrossing species are rapidly sterilized due to ovarian sperm invasion.[11] The simplification of the male proteome in selfing species suggests that many factors could contribute to invasivity.[13][,][15][,][16] However, restoration of just MSS to the self-fertile C. briggsae is sufficient to induce mild invasivity. Further, MSS+ sperm appear to derive their competitive advantage from this behavior, directly linking interspecies incompatibility with intraspecific competition. MSS-related proteins (MSRPs) remaining in the C. briggsae genome are similar in structure, expression, and localization to MSS but are not necessary for normal sperm competitiveness. Further, overexpression of the MSRP most similar to MSS, Cbr-MSRP-3, is insufficient to enhance competitiveness. We conclude that outcrossing species retain sperm competition factors that contribute to their reproductive isolation from selfing relatives that lost them.
Additional Links: PMID-39884276
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PubMed:
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@article {pmid39884276,
year = {2025},
author = {Van Goor, J and Turdiev, A and Speir, SJ and Manning, J and Haag, ES},
title = {Male secreted short glycoproteins link sperm competition to the reproductive isolation of species.},
journal = {Current biology : CB},
volume = {35},
number = {4},
pages = {911-917.e5},
doi = {10.1016/j.cub.2024.12.040},
pmid = {39884276},
issn = {1879-0445},
mesh = {Animals ; Male ; *Spermatozoa/physiology/metabolism ; *Reproductive Isolation ; Glycoproteins/metabolism/genetics ; Female ; Caenorhabditis elegans/physiology/genetics/metabolism ; },
abstract = {Sperm competition is found across multicellular organisms[1][,][2][,][3][,][4] using both external and internal fertilization.[5][,][6] Sperm competition and post-copulatory cryptic female choice can promote incompatibility between species due to the antagonistic coevolution of the sexes within a species.[7][,][8][,][9][,][10][,][11] This between-species incompatibility is accelerated and markedly asymmetrical when sexual mode differs, producing the "weak inbreeder, strong outcrosser" (WISO) pattern.[12] Here, we show that male secreted short (MSS) sperm glycoproteins of nematodes constitute a gametic effector of WISO. In obligately outcrossing Caenorhabditis, MSS is dispensable for baseline fertility but required for intraspecific sperm competitiveness.[13] MSS is lost in self-fertile lineages, likely as a response to selection for a hermaphrodite-biased sex ratio.[14] Selfing hermaphrodites that mate with males of closely related outcrossing species are rapidly sterilized due to ovarian sperm invasion.[11] The simplification of the male proteome in selfing species suggests that many factors could contribute to invasivity.[13][,][15][,][16] However, restoration of just MSS to the self-fertile C. briggsae is sufficient to induce mild invasivity. Further, MSS+ sperm appear to derive their competitive advantage from this behavior, directly linking interspecies incompatibility with intraspecific competition. MSS-related proteins (MSRPs) remaining in the C. briggsae genome are similar in structure, expression, and localization to MSS but are not necessary for normal sperm competitiveness. Further, overexpression of the MSRP most similar to MSS, Cbr-MSRP-3, is insufficient to enhance competitiveness. We conclude that outcrossing species retain sperm competition factors that contribute to their reproductive isolation from selfing relatives that lost them.},
}
MeSH Terms:
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Animals
Male
*Spermatozoa/physiology/metabolism
*Reproductive Isolation
Glycoproteins/metabolism/genetics
Female
Caenorhabditis elegans/physiology/genetics/metabolism
RevDate: 2025-02-23
CmpDate: 2025-02-23
Organ-on-a-chip: Quo vademus? Applications and regulatory status.
Colloids and surfaces. B, Biointerfaces, 249:114507.
Organ-on-a-chip systems, also referred to as microphysiological systems (MPS), represent an advance in bioengineering microsystems designed to mimic key aspects of human organ physiology and function. Drawing inspiration from the intricate and hierarchical architecture of the human body, these innovative platforms have emerged as invaluable in vitro tools with wide-ranging applications in drug discovery and development, as well as in enhancing our understanding of disease physiology. The facility to replicate human tissues within physiologically relevant three-dimensional multicellular environments empowers organ-on-a-chip systems with versatility throughout different stages of the drug development process. Moreover, these systems can be tailored to mimic specific disease states, facilitating the investigation of disease progression, drug responses, and potential therapeutic interventions. In particular, they can demonstrate, in early-phase pre-clinical studies, the safety and toxicity profiles of potential therapeutic compounds. Furthermore, they play a pivotal role in the in vitro evaluation of drug efficacy and the modeling of human diseases. One of the most promising prospects of organ-on-a-chip technology is to simulate the pathophysiology of specific subpopulations and even individual patients, thereby being used in personalized medicine. By mimicking the physiological responses of diverse patient groups, these systems hold the promise of revolutionizing therapeutic strategies, guiding them towards tailored intervention to the unique needs of each patient. This review presents the development status and evolution of microfluidic platforms that have facilitated the transition from cells to organs recreated on chips and some of the opportunities and applications offered by organ-on-a-chip technology. Additionally, the current potential and future perspectives of these microphysiological systems and the challenges this technology still faces are discussed.
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@article {pmid39826309,
year = {2025},
author = {Mendes, M and Morais, AS and Carlos, A and Sousa, JJ and Pais, AC and Mihăilă, SM and Vitorino, C},
title = {Organ-on-a-chip: Quo vademus? Applications and regulatory status.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {249},
number = {},
pages = {114507},
doi = {10.1016/j.colsurfb.2025.114507},
pmid = {39826309},
issn = {1873-4367},
mesh = {Humans ; *Lab-On-A-Chip Devices ; Drug Discovery ; Animals ; Microphysiological Systems ; },
abstract = {Organ-on-a-chip systems, also referred to as microphysiological systems (MPS), represent an advance in bioengineering microsystems designed to mimic key aspects of human organ physiology and function. Drawing inspiration from the intricate and hierarchical architecture of the human body, these innovative platforms have emerged as invaluable in vitro tools with wide-ranging applications in drug discovery and development, as well as in enhancing our understanding of disease physiology. The facility to replicate human tissues within physiologically relevant three-dimensional multicellular environments empowers organ-on-a-chip systems with versatility throughout different stages of the drug development process. Moreover, these systems can be tailored to mimic specific disease states, facilitating the investigation of disease progression, drug responses, and potential therapeutic interventions. In particular, they can demonstrate, in early-phase pre-clinical studies, the safety and toxicity profiles of potential therapeutic compounds. Furthermore, they play a pivotal role in the in vitro evaluation of drug efficacy and the modeling of human diseases. One of the most promising prospects of organ-on-a-chip technology is to simulate the pathophysiology of specific subpopulations and even individual patients, thereby being used in personalized medicine. By mimicking the physiological responses of diverse patient groups, these systems hold the promise of revolutionizing therapeutic strategies, guiding them towards tailored intervention to the unique needs of each patient. This review presents the development status and evolution of microfluidic platforms that have facilitated the transition from cells to organs recreated on chips and some of the opportunities and applications offered by organ-on-a-chip technology. Additionally, the current potential and future perspectives of these microphysiological systems and the challenges this technology still faces are discussed.},
}
MeSH Terms:
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Humans
*Lab-On-A-Chip Devices
Drug Discovery
Animals
Microphysiological Systems
RevDate: 2025-02-21
CmpDate: 2025-02-21
Establishment and maintenance of embryogenic cell fate during microspore embryogenesis.
The Plant journal : for cell and molecular biology, 121(4):e17243.
Microspore embryogenesis is a type of in vitro totipotency in which the immature male gametophyte (pollen) develops into a haploid embryo after an abiotic stress treatment. In Brassica napus, heat-stress treatment of male gametophytes induces the development of different types of multicellular embryogenic structures, each with different cellular characteristics and the capacity to form a differentiated embryo. The origin and early development of these different embryogenic structures have not been determined. We used two-photon excitation fluorescence microscopy and time-lapse imaging of cells expressing either a LEAFY COTYLEDON1 (LEC1) embryo identity reporter or a DR5v2 auxin response reporter to follow the development of embryogenic structures starting at the single- to few-cell stage. We show for the first time that the developmental fate of embryogenic structures is defined by the symmetry of the first embryogenic division and that the division plane also predicts the timing of subsequent pollen wall (exine) rupture: suspensorless embryos develop after a symmetric division and undergo late exine rupture, while suspensor-bearing embryos and embryogenic callus develop after an asymmetric division and undergo early exine rupture. Live imaging also captured previously unknown dynamic LEC1 and DR5v2 expression patterns that are associated with changes in exine integrity. This study highlights the developmental plasticity of cultured pollen and uncovers new roles for the first embryogenic cell division plane and the exine in defining and maintaining cell fate during microspore embryogenesis.
Additional Links: PMID-39981724
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@article {pmid39981724,
year = {2025},
author = {Siemons, C and Jonkers, S and Vlieg, RC and Corral-Martínez, P and van Noort, J and Boutilier, K},
title = {Establishment and maintenance of embryogenic cell fate during microspore embryogenesis.},
journal = {The Plant journal : for cell and molecular biology},
volume = {121},
number = {4},
pages = {e17243},
doi = {10.1111/tpj.17243},
pmid = {39981724},
issn = {1365-313X},
support = {656579//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; 435005024/ZONMW_/ZonMw/Netherlands ; 737.016.013//NWO Building Blocks of Life/ ; },
mesh = {*Pollen/genetics/cytology/embryology ; *Brassica napus/genetics/embryology/cytology ; Seeds/genetics/cytology/growth & development ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism/genetics ; Indoleacetic Acids/metabolism ; Cell Differentiation ; Time-Lapse Imaging ; Plants, Genetically Modified ; },
abstract = {Microspore embryogenesis is a type of in vitro totipotency in which the immature male gametophyte (pollen) develops into a haploid embryo after an abiotic stress treatment. In Brassica napus, heat-stress treatment of male gametophytes induces the development of different types of multicellular embryogenic structures, each with different cellular characteristics and the capacity to form a differentiated embryo. The origin and early development of these different embryogenic structures have not been determined. We used two-photon excitation fluorescence microscopy and time-lapse imaging of cells expressing either a LEAFY COTYLEDON1 (LEC1) embryo identity reporter or a DR5v2 auxin response reporter to follow the development of embryogenic structures starting at the single- to few-cell stage. We show for the first time that the developmental fate of embryogenic structures is defined by the symmetry of the first embryogenic division and that the division plane also predicts the timing of subsequent pollen wall (exine) rupture: suspensorless embryos develop after a symmetric division and undergo late exine rupture, while suspensor-bearing embryos and embryogenic callus develop after an asymmetric division and undergo early exine rupture. Live imaging also captured previously unknown dynamic LEC1 and DR5v2 expression patterns that are associated with changes in exine integrity. This study highlights the developmental plasticity of cultured pollen and uncovers new roles for the first embryogenic cell division plane and the exine in defining and maintaining cell fate during microspore embryogenesis.},
}
MeSH Terms:
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*Pollen/genetics/cytology/embryology
*Brassica napus/genetics/embryology/cytology
Seeds/genetics/cytology/growth & development
Gene Expression Regulation, Plant
Plant Proteins/metabolism/genetics
Indoleacetic Acids/metabolism
Cell Differentiation
Time-Lapse Imaging
Plants, Genetically Modified
RevDate: 2025-02-20
CmpDate: 2025-02-20
PI3Kα-specific inhibitor BYL-719 synergizes with cisplatin in vitro in PIK3CA-mutated ovarian cancer cells.
Scientific reports, 15(1):6265.
Peritoneal carcinomatosis in ovarian cancer is often associated with ascites where cancer cells grow as aggregates. Given the emerging evidence that multicellular growth enhances resistance to conventional therapies, and that patients frequently develop resistance to platinum salts, we investigated the efficiency of PI3K/Akt signalling pathway targeting in multicellular growth and its importance as a potential therapeutic target in cells resistant to platinum salts. Due to its importance in many cancers and to the frequent mutations of its encoding gene PIK3CA, we focused on targeting PI3Kα using BYL-719 (Alpelisib), an isoform-specific inhibitor already used in clinics. We used a panel of 3 ovarian cancer cell lines, SKOV-3, EFO-21 and OVCAR-3, which come from different histological origins and bear different mutations. PI3K targeting drugs inhibit the activity of the PI3K/Akt pathway in all tested ovarian cancer cell lines with a drastic reduction of the phosphorylation of Akt on the serine 473, regardless the histology or the mutational profile. We showed that when cultured in 3D aggregates, ovarian cancer cells are more resistant to the PI3Kα-specific inhibitor BYL-719 and cisplatin compared to 2D monolayers. BYL-719 synergizes with cisplatin in 3D cultures only in PIK3CA-mutated SKOV-3 cells. This drug combination leads to a major cytotoxicity in 3D aggregates of this cell line. Finally, BYL-719 in combination with cisplatin remains active in 3D aggregates of SKOV-3 cells co-cultured with mesenchymal stem cells. We have identified a signalling pathway of interest for the treatment of advanced ovarian cancer in vitro, which could limit the progression of this disease. These data pave the road to investigate whether PI3Kα-specific inhibitor BYL-719 should be proposed in combination with cisplatin, in priority in patients bearing a PIK3CA mutation.
Additional Links: PMID-39979449
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@article {pmid39979449,
year = {2025},
author = {Thibault, B and Thole, A and D'Angelo, R and Basset, C and Guillermet-Guibert, J},
title = {PI3Kα-specific inhibitor BYL-719 synergizes with cisplatin in vitro in PIK3CA-mutated ovarian cancer cells.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6265},
pmid = {39979449},
issn = {2045-2322},
support = {ARCPGA2022120005630_6362//Foundation for Cancer Research (ARC)/ ; TOUCAN//ANR/ ; },
mesh = {Humans ; *Cisplatin/pharmacology ; Female ; *Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/metabolism ; *Ovarian Neoplasms/drug therapy/genetics/pathology/metabolism ; Cell Line, Tumor ; *Drug Synergism ; *Mutation ; *Thiazoles/pharmacology ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism/antagonists & inhibitors ; Signal Transduction/drug effects ; Antineoplastic Agents/pharmacology ; Drug Resistance, Neoplasm/drug effects/genetics ; },
abstract = {Peritoneal carcinomatosis in ovarian cancer is often associated with ascites where cancer cells grow as aggregates. Given the emerging evidence that multicellular growth enhances resistance to conventional therapies, and that patients frequently develop resistance to platinum salts, we investigated the efficiency of PI3K/Akt signalling pathway targeting in multicellular growth and its importance as a potential therapeutic target in cells resistant to platinum salts. Due to its importance in many cancers and to the frequent mutations of its encoding gene PIK3CA, we focused on targeting PI3Kα using BYL-719 (Alpelisib), an isoform-specific inhibitor already used in clinics. We used a panel of 3 ovarian cancer cell lines, SKOV-3, EFO-21 and OVCAR-3, which come from different histological origins and bear different mutations. PI3K targeting drugs inhibit the activity of the PI3K/Akt pathway in all tested ovarian cancer cell lines with a drastic reduction of the phosphorylation of Akt on the serine 473, regardless the histology or the mutational profile. We showed that when cultured in 3D aggregates, ovarian cancer cells are more resistant to the PI3Kα-specific inhibitor BYL-719 and cisplatin compared to 2D monolayers. BYL-719 synergizes with cisplatin in 3D cultures only in PIK3CA-mutated SKOV-3 cells. This drug combination leads to a major cytotoxicity in 3D aggregates of this cell line. Finally, BYL-719 in combination with cisplatin remains active in 3D aggregates of SKOV-3 cells co-cultured with mesenchymal stem cells. We have identified a signalling pathway of interest for the treatment of advanced ovarian cancer in vitro, which could limit the progression of this disease. These data pave the road to investigate whether PI3Kα-specific inhibitor BYL-719 should be proposed in combination with cisplatin, in priority in patients bearing a PIK3CA mutation.},
}
MeSH Terms:
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hide MeSH Terms
Humans
*Cisplatin/pharmacology
Female
*Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/metabolism
*Ovarian Neoplasms/drug therapy/genetics/pathology/metabolism
Cell Line, Tumor
*Drug Synergism
*Mutation
*Thiazoles/pharmacology
Phosphoinositide-3 Kinase Inhibitors/pharmacology
Proto-Oncogene Proteins c-akt/metabolism/antagonists & inhibitors
Signal Transduction/drug effects
Antineoplastic Agents/pharmacology
Drug Resistance, Neoplasm/drug effects/genetics
RevDate: 2025-02-20
CmpDate: 2025-02-20
Homochirality in the Vicsek model: Fluctuations and potential implications for cellular flocks.
Physical review. E, 111(1-2):015427.
Chirality is a feature of many biological systems, and much research has been focused on understanding the origin and implications of this property. Famously, sugars and amino acids found in nature are homochiral, i.e., chiral symmetry is broken and only one of the two possible chiral states is ever observed. Certain types of cells show chiral behavior, too. Understanding the origin of cellular chirality and its effect on tissues and cellular dynamics is still an open problem and subject to much (recent) research, e.g., in the context of drosophila morphogenesis. Here, we develop a simple model to describe the possible origin of homochirality in cells. Combining the Vicsek model for collective behavior with the model of Jafarpour et al. [Phys. Rev. Lett. 115, 158101 (2015)0031-900710.1103/PhysRevLett.115.158101], developed to describe the emergence of molecular homochirality, we investigate how a homochiral state might have evolved in cells from an initially symmetric state without any mechanisms that explicitly break chiral symmetry. We investigate the transition to homochirality and show how the "openness" of the system as well as noise determine if and when a globally homochiral state is reached. While hypothetical and explorative in nature, our analysis may serve as a starting point for more realistic models of chirality in flocking multicellular systems.
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@article {pmid39972731,
year = {2025},
author = {Hoffmann, LA and Giomi, L},
title = {Homochirality in the Vicsek model: Fluctuations and potential implications for cellular flocks.},
journal = {Physical review. E},
volume = {111},
number = {1-2},
pages = {015427},
doi = {10.1103/PhysRevE.111.015427},
pmid = {39972731},
issn = {2470-0053},
mesh = {*Models, Biological ; Animals ; },
abstract = {Chirality is a feature of many biological systems, and much research has been focused on understanding the origin and implications of this property. Famously, sugars and amino acids found in nature are homochiral, i.e., chiral symmetry is broken and only one of the two possible chiral states is ever observed. Certain types of cells show chiral behavior, too. Understanding the origin of cellular chirality and its effect on tissues and cellular dynamics is still an open problem and subject to much (recent) research, e.g., in the context of drosophila morphogenesis. Here, we develop a simple model to describe the possible origin of homochirality in cells. Combining the Vicsek model for collective behavior with the model of Jafarpour et al. [Phys. Rev. Lett. 115, 158101 (2015)0031-900710.1103/PhysRevLett.115.158101], developed to describe the emergence of molecular homochirality, we investigate how a homochiral state might have evolved in cells from an initially symmetric state without any mechanisms that explicitly break chiral symmetry. We investigate the transition to homochirality and show how the "openness" of the system as well as noise determine if and when a globally homochiral state is reached. While hypothetical and explorative in nature, our analysis may serve as a starting point for more realistic models of chirality in flocking multicellular systems.},
}
MeSH Terms:
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*Models, Biological
Animals
RevDate: 2025-02-19
CmpDate: 2025-02-19
Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.
Nucleic acids research, 53(4):.
Cancer cells are highly plastic, favoring adaptation to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in several cell types: human embryonic stem cells, normal primary B-cells, primary chronic lymphocytic leukemia malignant B-cells, and primary colorectal cancer samples. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA polymerase II, Polycomb, and the lamina, respectively. Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.
Additional Links: PMID-39970295
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@article {pmid39970295,
year = {2025},
author = {Raynal, F and Sengupta, K and Plewczynski, D and Aliaga, B and Pancaldi, V},
title = {Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.},
journal = {Nucleic acids research},
volume = {53},
number = {4},
pages = {},
doi = {10.1093/nar/gkaf084},
pmid = {39970295},
issn = {1362-4962},
support = {//Fondation Toulouse Cancer Santé/ ; //Pierre Fabre Foundation for Research/ ; ANR-23-CE12-0023//Agence Nationale de la Recherche/ ; //Warsaw University of Technology/ ; 2020/37/B/NZ2/03757//National Science Centre/ ; },
mesh = {Humans ; *Cell Differentiation/genetics ; *Chromatin/metabolism/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Neoplastic ; Chromatin Assembly and Disassembly/genetics ; RNA Polymerase II/metabolism/genetics ; Embryonic Stem Cells/metabolism ; Polycomb-Group Proteins/genetics/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics/pathology ; Colorectal Neoplasms/genetics/pathology ; Epigenesis, Genetic ; Neoplasms/genetics/pathology ; },
abstract = {Cancer cells are highly plastic, favoring adaptation to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in several cell types: human embryonic stem cells, normal primary B-cells, primary chronic lymphocytic leukemia malignant B-cells, and primary colorectal cancer samples. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA polymerase II, Polycomb, and the lamina, respectively. Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Cell Differentiation/genetics
*Chromatin/metabolism/genetics
*Evolution, Molecular
Gene Expression Regulation, Neoplastic
Chromatin Assembly and Disassembly/genetics
RNA Polymerase II/metabolism/genetics
Embryonic Stem Cells/metabolism
Polycomb-Group Proteins/genetics/metabolism
Leukemia, Lymphocytic, Chronic, B-Cell/genetics/pathology
Colorectal Neoplasms/genetics/pathology
Epigenesis, Genetic
Neoplasms/genetics/pathology
RevDate: 2025-02-19
CmpDate: 2025-02-19
[Structure and Function of the Transglutaminase Cluster in the Basal Metazoan Halisarca dujardinii (Sponge)].
Molekuliarnaia biologiia, 58(5):797-810.
Transglutaminases are enzymes that carry out post-translational modifications of proteins and participate in the regulation of their activities. Here, we show for the first time that the transglutaminase genes in the basal metazoan, the sea sponge Halisarca dujardinii, are organized in a cluster, similarly to mammalian transglutaminases. The regulatory regions of six transglutaminase genes and their differential expression in the course of the life cycle of H. dujardinii suggest independent regulation of these genes. The decrease in transglutaminase activities by cystamine facilitates restoration of the multicellular structures of this sponge after its mechanical dissociation. For the first time we observed that this decrease in transglutaminase activities was accompanied by generation of the reactive oxygen species in the cells of a basal metazoan. The study of transglutaminases in the basal metazoans and other sea-dwelling organisms might provide better understanding of the evolution and specific functions of these enzymes in higher animals.
Additional Links: PMID-39970120
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@article {pmid39970120,
year = {2024},
author = {Finoshin, AD and Kravchuk, OI and Mikhailov, KV and Ziganshin, RH and Adameyko, KI and Mikhailov, VS and Lyupina, YV},
title = {[Structure and Function of the Transglutaminase Cluster in the Basal Metazoan Halisarca dujardinii (Sponge)].},
journal = {Molekuliarnaia biologiia},
volume = {58},
number = {5},
pages = {797-810},
pmid = {39970120},
issn = {0026-8984},
mesh = {Animals ; *Transglutaminases/genetics/metabolism ; *Porifera/enzymology/genetics ; Multigene Family ; Reactive Oxygen Species/metabolism ; Cystamine ; Gene Expression Regulation, Enzymologic ; },
abstract = {Transglutaminases are enzymes that carry out post-translational modifications of proteins and participate in the regulation of their activities. Here, we show for the first time that the transglutaminase genes in the basal metazoan, the sea sponge Halisarca dujardinii, are organized in a cluster, similarly to mammalian transglutaminases. The regulatory regions of six transglutaminase genes and their differential expression in the course of the life cycle of H. dujardinii suggest independent regulation of these genes. The decrease in transglutaminase activities by cystamine facilitates restoration of the multicellular structures of this sponge after its mechanical dissociation. For the first time we observed that this decrease in transglutaminase activities was accompanied by generation of the reactive oxygen species in the cells of a basal metazoan. The study of transglutaminases in the basal metazoans and other sea-dwelling organisms might provide better understanding of the evolution and specific functions of these enzymes in higher animals.},
}
MeSH Terms:
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Animals
*Transglutaminases/genetics/metabolism
*Porifera/enzymology/genetics
Multigene Family
Reactive Oxygen Species/metabolism
Cystamine
Gene Expression Regulation, Enzymologic
RevDate: 2025-02-18
CmpDate: 2025-02-18
Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.
Nucleic acids research, 53(4):.
Cancer cells are highly plastic, favoring adaptation to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in several cell types: human embryonic stem cells, normal primary B-cells, primary chronic lymphocytic leukemia malignant B-cells, and primary colorectal cancer samples. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA polymerase II, Polycomb, and the lamina, respectively. Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.
Additional Links: PMID-39964480
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PubMed:
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@article {pmid39964480,
year = {2025},
author = {Raynal, F and Sengupta, K and Plewczynski, D and Aliaga, B and Pancaldi, V},
title = {Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.},
journal = {Nucleic acids research},
volume = {53},
number = {4},
pages = {},
doi = {10.1093/nar/gkaf084},
pmid = {39964480},
issn = {1362-4962},
support = {//Fondation Toulouse Cancer Santé/ ; //Pierre Fabre Foundation for Research/ ; ANR-23-CE12-0023//Agence Nationale de la Recherche/ ; //Warsaw University of Technology/ ; 2020/37/B/NZ2/03757//National Science Centre/ ; },
mesh = {Humans ; *Cell Differentiation/genetics ; *Chromatin/metabolism/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Neoplastic ; Chromatin Assembly and Disassembly/genetics ; RNA Polymerase II/metabolism/genetics ; Embryonic Stem Cells/metabolism ; Polycomb-Group Proteins/genetics/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics/pathology ; Colorectal Neoplasms/genetics/pathology ; Epigenesis, Genetic ; Neoplasms/genetics/pathology ; },
abstract = {Cancer cells are highly plastic, favoring adaptation to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in several cell types: human embryonic stem cells, normal primary B-cells, primary chronic lymphocytic leukemia malignant B-cells, and primary colorectal cancer samples. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA polymerase II, Polycomb, and the lamina, respectively. Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Cell Differentiation/genetics
*Chromatin/metabolism/genetics
*Evolution, Molecular
Gene Expression Regulation, Neoplastic
Chromatin Assembly and Disassembly/genetics
RNA Polymerase II/metabolism/genetics
Embryonic Stem Cells/metabolism
Polycomb-Group Proteins/genetics/metabolism
Leukemia, Lymphocytic, Chronic, B-Cell/genetics/pathology
Colorectal Neoplasms/genetics/pathology
Epigenesis, Genetic
Neoplasms/genetics/pathology
RevDate: 2025-02-13
CmpDate: 2025-02-13
Single cell-derived multicellular meristem: insights into male-to-hermaphrodite conversion and de novo meristem formation in Ceratopteris.
Development (Cambridge, England), 152(3):.
Land plants alternate between asexual sporophytes and sexual gametophytes. Unlike seed plants, ferns develop free-living gametophytes. Gametophytes of the model fern Ceratopteris exhibit two sex types: hermaphrodites with pluripotent meristems and males lacking meristems. In the absence of the pheromone antheridiogen, males convert to hermaphrodites by forming de novo meristems, although the mechanisms remain unclear. Using long-term time-lapse imaging and computational analyses, we captured male-to-hermaphrodite conversion at single-cell resolution and reconstructed the lineage and division atlas of newly formed meristems. Lineage tracing revealed that the de novo-formed meristem originates from a single non-antheridium cell: the meristem progenitor cell (MPC). During conversion, the MPC lineage showed increased mitotic activity, with marginal cells proliferating faster than inner cells. A mathematical model suggested that stochastic variation in cell division, combined with strong inhibitory signals from dividing marginal cells, is sufficient to explain gametophyte dynamics. Experimental disruption of division timing agreed with the model, showing that precise cell cycle progression is essential for MPC establishment and sex-type conversion. These findings reveal cellular mechanisms governing sex conversion and de novo meristem formation in land plants.
Additional Links: PMID-39817858
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@article {pmid39817858,
year = {2025},
author = {Yang, X and Yan, A and Liu, X and Volkening, A and Zhou, Y},
title = {Single cell-derived multicellular meristem: insights into male-to-hermaphrodite conversion and de novo meristem formation in Ceratopteris.},
journal = {Development (Cambridge, England)},
volume = {152},
number = {3},
pages = {},
doi = {10.1242/dev.204411},
pmid = {39817858},
issn = {1477-9129},
support = {IOS 1931114//National Science Foundation/ ; NSF DMS 1764421//Northwestern University/ ; SFARI 597491-RWC//Simons Foundation/ ; R01GM157611/GM/NIGMS NIH HHS/United States ; },
mesh = {*Meristem/cytology/metabolism/growth & development ; Pteridaceae/metabolism/genetics ; Cell Lineage ; Germ Cells, Plant/cytology/metabolism/growth & development ; Cell Division ; },
abstract = {Land plants alternate between asexual sporophytes and sexual gametophytes. Unlike seed plants, ferns develop free-living gametophytes. Gametophytes of the model fern Ceratopteris exhibit two sex types: hermaphrodites with pluripotent meristems and males lacking meristems. In the absence of the pheromone antheridiogen, males convert to hermaphrodites by forming de novo meristems, although the mechanisms remain unclear. Using long-term time-lapse imaging and computational analyses, we captured male-to-hermaphrodite conversion at single-cell resolution and reconstructed the lineage and division atlas of newly formed meristems. Lineage tracing revealed that the de novo-formed meristem originates from a single non-antheridium cell: the meristem progenitor cell (MPC). During conversion, the MPC lineage showed increased mitotic activity, with marginal cells proliferating faster than inner cells. A mathematical model suggested that stochastic variation in cell division, combined with strong inhibitory signals from dividing marginal cells, is sufficient to explain gametophyte dynamics. Experimental disruption of division timing agreed with the model, showing that precise cell cycle progression is essential for MPC establishment and sex-type conversion. These findings reveal cellular mechanisms governing sex conversion and de novo meristem formation in land plants.},
}
MeSH Terms:
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*Meristem/cytology/metabolism/growth & development
Pteridaceae/metabolism/genetics
Cell Lineage
Germ Cells, Plant/cytology/metabolism/growth & development
Cell Division
RevDate: 2025-02-12
CmpDate: 2025-02-12
Intercellular adhesion boots collective cell migration through elevated membrane tension.
Nature communications, 16(1):1588.
In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Mediators of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. Here, we address this question through artificial photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.
Additional Links: PMID-39939306
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@article {pmid39939306,
year = {2025},
author = {Bijonowski, BM and Park, J and Bergert, M and Teubert, C and Diz-Muñoz, A and Galic, M and Wegner, SV},
title = {Intercellular adhesion boots collective cell migration through elevated membrane tension.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1588},
pmid = {39939306},
issn = {2041-1723},
support = {757593//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; GA2268/4-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 386797833//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
mesh = {*Cell Movement ; *Cell Adhesion/physiology ; *Cell Membrane/metabolism ; *Phospholipase D/metabolism ; Humans ; Animals ; Cytoskeleton/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Phosphatidic Acids/metabolism ; Signal Transduction ; },
abstract = {In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Mediators of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. Here, we address this question through artificial photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Cell Movement
*Cell Adhesion/physiology
*Cell Membrane/metabolism
*Phospholipase D/metabolism
Humans
Animals
Cytoskeleton/metabolism
TOR Serine-Threonine Kinases/metabolism
Phosphatidic Acids/metabolism
Signal Transduction
RevDate: 2025-02-11
CmpDate: 2025-02-11
Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel.
Proceedings of the National Academy of Sciences of the United States of America, 122(7):e2421623122.
Acidic glycans are essential for the biology of multicellular eukaryotes. To utilize them, microbial life including symbionts and pathogens has evolved polysaccharide lyases (PL) that cleave their 1,4 glycosidic linkages via a β-elimination mechanism. PL family 33 (PL33) enzymes have the unusual ability to target a diverse range of glycosaminoglycans (GAGs), as well as the bacterial polymer, gellan gum. In order to gain more detailed insight into PL33 activities we recombinantly expressed 10 PL33 members derived from all major environments and further elucidated the detailed biochemical and biophysical properties of five, showing that their substrate specificity is conferred by variations in tunnel length and topography. The key amino acids involved in catalysis and substrate interactions were identified, and employing a combination of complementary biochemical, structural, and modeling approaches, we show that the tunnel topography is induced by substrate binding to the glycan. Structural and bioinformatic analyses revealed that these features are conserved across several lyase families as well as in mammalian GAG epimerases.
Additional Links: PMID-39932998
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@article {pmid39932998,
year = {2025},
author = {Loiodice, M and Drula, E and McIver, Z and Antonyuk, S and Baslé, A and Lima, M and Yates, EA and Byrne, DP and Coughlan, J and Leech, A and Mesdaghi, S and Rigden, DJ and Drouillard, S and Helbert, W and Henrissat, B and Terrapon, N and Wright, GSA and Couturier, M and Cartmell, A},
title = {Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {7},
pages = {e2421623122},
doi = {10.1073/pnas.2421623122},
pmid = {39932998},
issn = {1091-6490},
mesh = {*Polysaccharide-Lyases/metabolism/genetics/chemistry ; Substrate Specificity ; Bacterial Proteins/metabolism/genetics/chemistry ; Bacteria/enzymology/genetics ; Evolution, Molecular ; Models, Molecular ; Amino Acid Sequence ; Binding Sites ; Protein Binding ; Polysaccharides/metabolism ; Glycosaminoglycans/metabolism ; },
abstract = {Acidic glycans are essential for the biology of multicellular eukaryotes. To utilize them, microbial life including symbionts and pathogens has evolved polysaccharide lyases (PL) that cleave their 1,4 glycosidic linkages via a β-elimination mechanism. PL family 33 (PL33) enzymes have the unusual ability to target a diverse range of glycosaminoglycans (GAGs), as well as the bacterial polymer, gellan gum. In order to gain more detailed insight into PL33 activities we recombinantly expressed 10 PL33 members derived from all major environments and further elucidated the detailed biochemical and biophysical properties of five, showing that their substrate specificity is conferred by variations in tunnel length and topography. The key amino acids involved in catalysis and substrate interactions were identified, and employing a combination of complementary biochemical, structural, and modeling approaches, we show that the tunnel topography is induced by substrate binding to the glycan. Structural and bioinformatic analyses revealed that these features are conserved across several lyase families as well as in mammalian GAG epimerases.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Polysaccharide-Lyases/metabolism/genetics/chemistry
Substrate Specificity
Bacterial Proteins/metabolism/genetics/chemistry
Bacteria/enzymology/genetics
Evolution, Molecular
Models, Molecular
Amino Acid Sequence
Binding Sites
Protein Binding
Polysaccharides/metabolism
Glycosaminoglycans/metabolism
RevDate: 2025-02-05
CmpDate: 2025-02-05
Physcomitrium LATERAL SUPPRESSOR genes promote formative cell divisions to produce germ cell lineages in both male and female gametangia.
The New phytologist, 245(5):2004-2015.
The evolution of green plants from aquatic to terrestrial environments is thought to have been facilitated by the acquisition of gametangia, specialized multicellular organs housing gametes. Antheridia and archegonia, responsible for producing and protecting sperm and egg cells, undergo formative cell divisions to produce a cell to differentiate into germ cell lineages and the other cell to give rise to surrounding structures. However, the genes governing this process remain unidentified. We isolated genes expressed during gametangia development from previously established gene-trap lines of Physcomitrium patens and characterized their function during gametangia formation. We identified P. patens LATERAL SUPPRESSOR 1 (PpLAS1) from the gene-trap library, encoding a GRAS transcription factor. The double-deletion mutant with its paralog PpLAS2 failed to form inner cells in both gametangia. PpLASs are expressed in cells undergoing formative cell division, and introducing PpLAS1 into the double-deletion mutant successfully rescued the phenotype. These findings underscore the pivotal role of PpLASs in regulating formative cell divisions, ensuring the separation of reproductive cell lineages from surrounding cells in antheridia and archegonia. Furthermore, they suggest a link between PpLASs and the evolutionary origin of male and female gametangia in the common ancestor of land plants.
Additional Links: PMID-39737561
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PubMed:
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@article {pmid39737561,
year = {2025},
author = {Horiuchi, Y and Umakawa, N and Otani, R and Tamada, Y and Kosetsu, K and Hiwatashi, Y and Wakisaka, R and Yoshida, S and Murata, T and Hasebe, M and Ishikawa, M and Kofuji, R},
title = {Physcomitrium LATERAL SUPPRESSOR genes promote formative cell divisions to produce germ cell lineages in both male and female gametangia.},
journal = {The New phytologist},
volume = {245},
number = {5},
pages = {2004-2015},
doi = {10.1111/nph.20372},
pmid = {39737561},
issn = {1469-8137},
mesh = {*Cell Division/genetics ; *Cell Lineage/genetics ; *Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism ; *Germ Cells, Plant/growth & development/cytology ; *Bryopsida/genetics/growth & development/cytology ; *Genes, Plant ; Transcription Factors/genetics/metabolism ; Ovule/genetics/growth & development/cytology ; Mutation/genetics ; Pollen/genetics/cytology/growth & development ; },
abstract = {The evolution of green plants from aquatic to terrestrial environments is thought to have been facilitated by the acquisition of gametangia, specialized multicellular organs housing gametes. Antheridia and archegonia, responsible for producing and protecting sperm and egg cells, undergo formative cell divisions to produce a cell to differentiate into germ cell lineages and the other cell to give rise to surrounding structures. However, the genes governing this process remain unidentified. We isolated genes expressed during gametangia development from previously established gene-trap lines of Physcomitrium patens and characterized their function during gametangia formation. We identified P. patens LATERAL SUPPRESSOR 1 (PpLAS1) from the gene-trap library, encoding a GRAS transcription factor. The double-deletion mutant with its paralog PpLAS2 failed to form inner cells in both gametangia. PpLASs are expressed in cells undergoing formative cell division, and introducing PpLAS1 into the double-deletion mutant successfully rescued the phenotype. These findings underscore the pivotal role of PpLASs in regulating formative cell divisions, ensuring the separation of reproductive cell lineages from surrounding cells in antheridia and archegonia. Furthermore, they suggest a link between PpLASs and the evolutionary origin of male and female gametangia in the common ancestor of land plants.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Cell Division/genetics
*Cell Lineage/genetics
*Gene Expression Regulation, Plant
*Plant Proteins/genetics/metabolism
*Germ Cells, Plant/growth & development/cytology
*Bryopsida/genetics/growth & development/cytology
*Genes, Plant
Transcription Factors/genetics/metabolism
Ovule/genetics/growth & development/cytology
Mutation/genetics
Pollen/genetics/cytology/growth & development
RevDate: 2025-02-05
CmpDate: 2025-02-05
Evolution of the ocular immune system.
Eye (London, England), 39(3):468-477.
The evolution of the ocular immune system should be viewed within the context of the evolution of the immune system, and indeed organisms, as a whole. Since the earliest time, the most primitive responses of single cell organisms involved molecules such as anti-microbial peptides and behaviours such as phagocytosis. Innate immunity took shape ~2.5 billion years ago while adaptive immunity and antigen specificity appeared with vertebrate evolution ~ 500 million years ago. The invention of the microscope and the germ theory of disease precipitated debate on cellular versus humoral immunity, resolved by the discovery of B and T cells. Most recently, our understanding of the microbiome and consideration of the host existing symbiotically with trillions of microbial genes (the holobiont), suggests that the immune system is a sensor of homoeostasis rather than simply a responder to pathogens. Each tissue type in multicellular organisms, such as vertebrates, has a customised response to immune challenge, with powerful reactions most evident in barrier tissues such as the skin and gut mucosa, while the eye and brain occupy the opposite extreme where responses are attenuated. The experimental background which historically led to the concept of immune privilege is discussed in this review; however, we propose that the ocular immune response should not be viewed as unique but simply an example of how the tissues variably respond in nature, more or less to the same challenge (or danger).
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@article {pmid39653763,
year = {2025},
author = {Forrester, JV and McMenamin, PG},
title = {Evolution of the ocular immune system.},
journal = {Eye (London, England)},
volume = {39},
number = {3},
pages = {468-477},
pmid = {39653763},
issn = {1476-5454},
mesh = {Humans ; Animals ; *Biological Evolution ; *Eye/immunology ; *Immune System/physiology/immunology ; *Immunity, Innate/physiology ; Adaptive Immunity ; },
abstract = {The evolution of the ocular immune system should be viewed within the context of the evolution of the immune system, and indeed organisms, as a whole. Since the earliest time, the most primitive responses of single cell organisms involved molecules such as anti-microbial peptides and behaviours such as phagocytosis. Innate immunity took shape ~2.5 billion years ago while adaptive immunity and antigen specificity appeared with vertebrate evolution ~ 500 million years ago. The invention of the microscope and the germ theory of disease precipitated debate on cellular versus humoral immunity, resolved by the discovery of B and T cells. Most recently, our understanding of the microbiome and consideration of the host existing symbiotically with trillions of microbial genes (the holobiont), suggests that the immune system is a sensor of homoeostasis rather than simply a responder to pathogens. Each tissue type in multicellular organisms, such as vertebrates, has a customised response to immune challenge, with powerful reactions most evident in barrier tissues such as the skin and gut mucosa, while the eye and brain occupy the opposite extreme where responses are attenuated. The experimental background which historically led to the concept of immune privilege is discussed in this review; however, we propose that the ocular immune response should not be viewed as unique but simply an example of how the tissues variably respond in nature, more or less to the same challenge (or danger).},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Animals
*Biological Evolution
*Eye/immunology
*Immune System/physiology/immunology
*Immunity, Innate/physiology
Adaptive Immunity
RevDate: 2025-01-31
CmpDate: 2025-02-01
Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications.
Scientific reports, 15(1):3933.
Tumoroids, sometimes referred to as cancer organoids, are patient-derived cancer cells grown as 3D, self-organized multicellular structures that maintain key characteristics (e.g., genotype, gene expression levels) of the tumor from which they originated. These models have emerged as valuable tools for studying tumor biology, cytotoxicity, and response of patient-derived cells to cancer therapies. However, the establishment and maintenance of tumoroids has historically been challenging, labor intensive, and highly variable from lab to lab, hindering their widespread use. Here, we characterize the establishment and/or expansion of colorectal, lung, head and neck, breast, pancreas, and endometrial tumoroids using the standardized, serum-free Gibco OncoPro Tumoroid Culture Medium. Newly derived tumoroid lines (n = 20) were analyzed by targeted genomic profiling and RNA sequencing and were representative of tumor tissue samples. Tumoroid lines were stable for over 250 days in culture and freeze-thaw competent. Previously established tumoroid lines were also transitioned to OncoPro medium and exhibited, on average, similar growth rates and conserved donor-specific characteristics when compared to original media systems. Additionally, OncoPro medium was compatible with both embedded culture in extracellular matrix and growth in a suspension format for facile culture and scale up. An example application of these models for assessing the cytotoxicity of a natural killer cell line and primary natural killer cells over time and at various doses demonstrated the compatibility of these models with assays used in compound and cell therapy development. We anticipate that the standardization and versatility of this approach will have important benefits for basic cancer research, drug discovery, and personalized medicine and help make tumoroid models more accessible to the cancer research community.
Additional Links: PMID-39890889
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@article {pmid39890889,
year = {2025},
author = {Paul, CD and Yankaskas, C and Shahi Thakuri, P and Balhouse, B and Salen, S and Bullock, A and Beam, S and Chatman, A and Djikeng, S and Yang, XJ and Wong, G and Dey, I and Holmes, S and Dockey, A and Bailey-Steinitz, L and Zheng, L and Li, W and Chandra, V and Nguyen, J and Sharp, J and Willems, E and Kennedy, M and Dallas, MR and Kuninger, D},
title = {Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {3933},
pmid = {39890889},
issn = {2045-2322},
mesh = {Humans ; *Neoplasms/pathology/genetics ; *Organoids/pathology/metabolism ; Cell Line, Tumor ; Female ; Cell Culture Techniques/methods ; Tumor Cells, Cultured ; },
abstract = {Tumoroids, sometimes referred to as cancer organoids, are patient-derived cancer cells grown as 3D, self-organized multicellular structures that maintain key characteristics (e.g., genotype, gene expression levels) of the tumor from which they originated. These models have emerged as valuable tools for studying tumor biology, cytotoxicity, and response of patient-derived cells to cancer therapies. However, the establishment and maintenance of tumoroids has historically been challenging, labor intensive, and highly variable from lab to lab, hindering their widespread use. Here, we characterize the establishment and/or expansion of colorectal, lung, head and neck, breast, pancreas, and endometrial tumoroids using the standardized, serum-free Gibco OncoPro Tumoroid Culture Medium. Newly derived tumoroid lines (n = 20) were analyzed by targeted genomic profiling and RNA sequencing and were representative of tumor tissue samples. Tumoroid lines were stable for over 250 days in culture and freeze-thaw competent. Previously established tumoroid lines were also transitioned to OncoPro medium and exhibited, on average, similar growth rates and conserved donor-specific characteristics when compared to original media systems. Additionally, OncoPro medium was compatible with both embedded culture in extracellular matrix and growth in a suspension format for facile culture and scale up. An example application of these models for assessing the cytotoxicity of a natural killer cell line and primary natural killer cells over time and at various doses demonstrated the compatibility of these models with assays used in compound and cell therapy development. We anticipate that the standardization and versatility of this approach will have important benefits for basic cancer research, drug discovery, and personalized medicine and help make tumoroid models more accessible to the cancer research community.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Neoplasms/pathology/genetics
*Organoids/pathology/metabolism
Cell Line, Tumor
Female
Cell Culture Techniques/methods
Tumor Cells, Cultured
RevDate: 2025-01-30
CmpDate: 2025-01-30
Oxygen-binding proteins aid oxygen diffusion to enhance fitness of a yeast model of multicellularity.
PLoS biology, 23(1):e3002975 pii:PBIOLOGY-D-24-00362.
Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We address this knowledge gap by heterologously expressing the oxygen-binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms when O2 is least limiting. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of oxygen-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.
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@article {pmid39883703,
year = {2025},
author = {Wong, W and Bravo, P and Yunker, PJ and Ratcliff, WC and Burnetti, AJ},
title = {Oxygen-binding proteins aid oxygen diffusion to enhance fitness of a yeast model of multicellularity.},
journal = {PLoS biology},
volume = {23},
number = {1},
pages = {e3002975},
doi = {10.1371/journal.pbio.3002975},
pmid = {39883703},
issn = {1545-7885},
mesh = {*Oxygen/metabolism ; *Saccharomyces cerevisiae/metabolism/genetics ; Diffusion ; Myoglobin/metabolism/genetics ; Hemerythrin/metabolism/genetics ; Models, Biological ; Genetic Fitness ; Oxygen Consumption ; },
abstract = {Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We address this knowledge gap by heterologously expressing the oxygen-binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms when O2 is least limiting. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of oxygen-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.},
}
MeSH Terms:
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*Oxygen/metabolism
*Saccharomyces cerevisiae/metabolism/genetics
Diffusion
Myoglobin/metabolism/genetics
Hemerythrin/metabolism/genetics
Models, Biological
Genetic Fitness
Oxygen Consumption
RevDate: 2025-01-30
Considerations for Domestication of Novel Strains of Filamentous Fungi.
ACS synthetic biology [Epub ahead of print].
Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.
Additional Links: PMID-39883596
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@article {pmid39883596,
year = {2025},
author = {Pullen, RM and Decker, SR and Subramanian, V and Adler, MJ and Tobias, AV and Perisin, M and Sund, CJ and Servinsky, MD and Kozlowski, MT},
title = {Considerations for Domestication of Novel Strains of Filamentous Fungi.},
journal = {ACS synthetic biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acssynbio.4c00672},
pmid = {39883596},
issn = {2161-5063},
abstract = {Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.},
}
RevDate: 2025-01-29
Molecular and functional convergences associated with complex multicellularity in Eukarya.
Molecular biology and evolution pii:7985930 [Epub ahead of print].
A key trait of Eukarya is the independent evolution of complex multicellular (CM) in animals, plants, fungi, brown algae and red algae. This phenotype is characterized by the initial exaptation of cell-cell adhesion genes followed by the emergence of mechanisms for cell-cell communication, together with the expansion of transcription factor gene families responsible for cell and tissue identity. The number of cell types (NCT) is commonly used as a quantitative proxy for biological complexity in comparative genomics studies. While expansions of individual gene families have been associated with NCT variation within individual CM lineages, the molecular and functional roles responsible for the independent evolution of CM across Eukarya remain poorly understood. We employed a phylogeny-aware strategy to conduct a genomic-scale search for associations between NCT and the abundance of genomic components across a phylogenetically diverse set of 81 eukaryotic species, including species from all CM lineages. Our annotation schemas represent two complimentary aspects of genomic information: homology - represented by conserved sequences - and function - represented by Gene Ontology (GO) terms. We found many gene families sharing common biological themes that define CM to be independently expanded in two or more CM lineages, such as components of the extracellular matrix, cell-cell communication mechanisms, and developmental pathways. Additionally, we describe many previously unknown associations of biological themes and biological complexity, such as mechanisms for wound response, immunity, cell migration, regulatory processes, and response to natural rhythms. Together, our findings unveil a set of functional and molecular convergences independently expanded in CM lineages likely due to the common selective pressures in their lifestyles.
Additional Links: PMID-39877976
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@article {pmid39877976,
year = {2025},
author = {Pereira Lobo, F and da Costa, DB and da Silva, TTM and de Oliveira, MD},
title = {Molecular and functional convergences associated with complex multicellularity in Eukarya.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msaf013},
pmid = {39877976},
issn = {1537-1719},
abstract = {A key trait of Eukarya is the independent evolution of complex multicellular (CM) in animals, plants, fungi, brown algae and red algae. This phenotype is characterized by the initial exaptation of cell-cell adhesion genes followed by the emergence of mechanisms for cell-cell communication, together with the expansion of transcription factor gene families responsible for cell and tissue identity. The number of cell types (NCT) is commonly used as a quantitative proxy for biological complexity in comparative genomics studies. While expansions of individual gene families have been associated with NCT variation within individual CM lineages, the molecular and functional roles responsible for the independent evolution of CM across Eukarya remain poorly understood. We employed a phylogeny-aware strategy to conduct a genomic-scale search for associations between NCT and the abundance of genomic components across a phylogenetically diverse set of 81 eukaryotic species, including species from all CM lineages. Our annotation schemas represent two complimentary aspects of genomic information: homology - represented by conserved sequences - and function - represented by Gene Ontology (GO) terms. We found many gene families sharing common biological themes that define CM to be independently expanded in two or more CM lineages, such as components of the extracellular matrix, cell-cell communication mechanisms, and developmental pathways. Additionally, we describe many previously unknown associations of biological themes and biological complexity, such as mechanisms for wound response, immunity, cell migration, regulatory processes, and response to natural rhythms. Together, our findings unveil a set of functional and molecular convergences independently expanded in CM lineages likely due to the common selective pressures in their lifestyles.},
}
RevDate: 2025-01-27
CmpDate: 2025-01-27
[The role of volatile organic compounds in plant-insect communication].
Biologie aujourd'hui, 218(3-4):141-144.
Insects and flowering plants are the most abundant and diverse multicellular organisms on Earth, accounting for 75% of known species. Their evolution has been largely interdependent since the so-called Angiosperm Terrestrial Revolution (100-50 Mya), when the explosion of plant diversity stimulated the evolution of pollinating and herbivorous insects. Plant-insect interactions rely heavily on chemical communication via volatile organic compounds (VOCs). These molecules are synthesised by the secondary metabolism of plants through various pathways and include terpenes, benzenoids and aliphatic compounds. As of today, more than 1,700 of these VOCs have notably been identified in flowers. Plants use these molecules to attract pollinators or repel herbivorous insects. VOCs also act as chemical signals for insects, helping them to find food or egg-laying sites. Chemical communication has thus played an important role in the evolutionary history of insects and flowering plants. Tritrophic interactions are a fascinating example of VOC-driven communication. When plants are attacked by herbivores, they emit herbivore-induced volatiles, such as green leaf volatiles and specific terpenes. These signals attract predators or parasitoids of the herbivores, acting as a chemical distress call. For example, parasitoid wasps can identify plants that have been attacked by their host herbivores, even in the absence of the herbivores themselves, thanks to the plant's odour profile. But herbivore-induced volatiles also affect the herbivores themselves. Female moths, for example, use these olfactory cues to avoid laying eggs on plants that have already been attacked. Insects detect VOCs using highly sensitive odorant receptors on their antennae. Herbivorous insects, such as the model moth species S. littoralis, have receptors specific for floral VOCs and herbivore-induced volatiles. Current research aims to understand how the evolution of these receptors has contributed to the adaptation of insects to plant volatiles. In moths, receptors for benzenoids appear to be more ancient and conserved, whereas receptors for terpenes and aliphatic molecules show more recent diversification in response to plant evolution. Research into plant-insect communication also opens up avenues for sustainable agriculture, as VOCs can be used to attract natural pest predators or deter herbivores, reducing the need for chemical pesticides.
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@article {pmid39868713,
year = {2024},
author = {Montagné, N},
title = {[The role of volatile organic compounds in plant-insect communication].},
journal = {Biologie aujourd'hui},
volume = {218},
number = {3-4},
pages = {141-144},
doi = {10.1051/jbio/2024016},
pmid = {39868713},
issn = {2105-0686},
mesh = {Animals ; *Volatile Organic Compounds/metabolism ; *Insecta/physiology ; *Plants/chemistry/metabolism/parasitology ; Herbivory/physiology ; Animal Communication ; Pollination/physiology ; },
abstract = {Insects and flowering plants are the most abundant and diverse multicellular organisms on Earth, accounting for 75% of known species. Their evolution has been largely interdependent since the so-called Angiosperm Terrestrial Revolution (100-50 Mya), when the explosion of plant diversity stimulated the evolution of pollinating and herbivorous insects. Plant-insect interactions rely heavily on chemical communication via volatile organic compounds (VOCs). These molecules are synthesised by the secondary metabolism of plants through various pathways and include terpenes, benzenoids and aliphatic compounds. As of today, more than 1,700 of these VOCs have notably been identified in flowers. Plants use these molecules to attract pollinators or repel herbivorous insects. VOCs also act as chemical signals for insects, helping them to find food or egg-laying sites. Chemical communication has thus played an important role in the evolutionary history of insects and flowering plants. Tritrophic interactions are a fascinating example of VOC-driven communication. When plants are attacked by herbivores, they emit herbivore-induced volatiles, such as green leaf volatiles and specific terpenes. These signals attract predators or parasitoids of the herbivores, acting as a chemical distress call. For example, parasitoid wasps can identify plants that have been attacked by their host herbivores, even in the absence of the herbivores themselves, thanks to the plant's odour profile. But herbivore-induced volatiles also affect the herbivores themselves. Female moths, for example, use these olfactory cues to avoid laying eggs on plants that have already been attacked. Insects detect VOCs using highly sensitive odorant receptors on their antennae. Herbivorous insects, such as the model moth species S. littoralis, have receptors specific for floral VOCs and herbivore-induced volatiles. Current research aims to understand how the evolution of these receptors has contributed to the adaptation of insects to plant volatiles. In moths, receptors for benzenoids appear to be more ancient and conserved, whereas receptors for terpenes and aliphatic molecules show more recent diversification in response to plant evolution. Research into plant-insect communication also opens up avenues for sustainable agriculture, as VOCs can be used to attract natural pest predators or deter herbivores, reducing the need for chemical pesticides.},
}
MeSH Terms:
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Animals
*Volatile Organic Compounds/metabolism
*Insecta/physiology
*Plants/chemistry/metabolism/parasitology
Herbivory/physiology
Animal Communication
Pollination/physiology
RevDate: 2025-01-25
Evolution of transcription factor-containing superfamilies in Eukaryotes.
Journal of molecular biology pii:S0022-2836(25)00025-7 [Epub ahead of print].
Regulation of gene expression helps determine various phenotypes in most cellular life forms. It is orchestrated at different levels and at the point of transcription initiation by transcription factors (TFs). TFs bind to DNA through domains that are evolutionarily related, by shared membership of the same superfamilies (TF-SFs), to those found in other nucleic acid binding and protein-binding functions (nTFs for non-TFs). Here we ask how TF DNA binding sequence families in eukaryotes have evolved in relation to their nTF relatives. TF numbers scale by power law with the total number of protein-coding genes differently in different clades, with fungi usually showing sub-linear powers whereas chordates show super-linear scaling. The LECA probably encoded a complex regulatory machinery with both TFs and nTFs, but with an excess of nTFs when compared to the relative distribution of TFs and nTFs in extant organisms. Losses drive the evolution of TFs and nTFs, with the possible exception of TFs in animals for some tree topologies. TFs are highly dynamic in evolution, showing higher gain and loss rates than nTFs though both are conserved to similar extents. Gains of TFs and nTFs are driven by the appearance of a large number of new sequence clusters in a small number of nodes, which determine the presence of as many as a third of extant TFs and nTFs as well as the relative presence of TFs and nTFs. Whereas nodes showing explosion of TF numbers belong to multicellular clades, those for nTFs lie among the fungi and the protists.
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@article {pmid39863161,
year = {2025},
author = {Dubey, A and Muthu, G and Narain Seshasayee, AS},
title = {Evolution of transcription factor-containing superfamilies in Eukaryotes.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {168959},
doi = {10.1016/j.jmb.2025.168959},
pmid = {39863161},
issn = {1089-8638},
abstract = {Regulation of gene expression helps determine various phenotypes in most cellular life forms. It is orchestrated at different levels and at the point of transcription initiation by transcription factors (TFs). TFs bind to DNA through domains that are evolutionarily related, by shared membership of the same superfamilies (TF-SFs), to those found in other nucleic acid binding and protein-binding functions (nTFs for non-TFs). Here we ask how TF DNA binding sequence families in eukaryotes have evolved in relation to their nTF relatives. TF numbers scale by power law with the total number of protein-coding genes differently in different clades, with fungi usually showing sub-linear powers whereas chordates show super-linear scaling. The LECA probably encoded a complex regulatory machinery with both TFs and nTFs, but with an excess of nTFs when compared to the relative distribution of TFs and nTFs in extant organisms. Losses drive the evolution of TFs and nTFs, with the possible exception of TFs in animals for some tree topologies. TFs are highly dynamic in evolution, showing higher gain and loss rates than nTFs though both are conserved to similar extents. Gains of TFs and nTFs are driven by the appearance of a large number of new sequence clusters in a small number of nodes, which determine the presence of as many as a third of extant TFs and nTFs as well as the relative presence of TFs and nTFs. Whereas nodes showing explosion of TF numbers belong to multicellular clades, those for nTFs lie among the fungi and the protists.},
}
RevDate: 2025-01-24
Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.
Microbiology and molecular biology reviews : MMBR [Epub ahead of print].
SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole. During colony differentiation, an almost infinite number of ecological and physiological population-forming forces are at work, creating complex, intricate colony structures with divergent functions. Understanding the assembly and dynamics of such populations requires resolving individual cells or cell groups within such macroscopic structures. Addressing how each cell contributes to the collective action requires pushing the resolution boundaries of key technologies that will be presented in this review. In particular, single-cell techniques provide powerful tools for studying bacterial multicellularity with unprecedented spatial and temporal resolution. These advancements include novel microscopic techniques, mass spectrometry imaging, flow cytometry, spatial transcriptomics, single-bacteria RNA sequencing, and the integration of spatiotemporal transcriptomics with microscopy, alongside advanced microfluidic cultivation systems. This review encourages exploring the synergistic potential of the new technologies in the study of bacterial multicellularity, with a particular focus on individuals in differentiated bacterial biofilms (colonies). It highlights how resolving population structures at the single-cell level and understanding their respective functions can elucidate the overarching functions of bacterial multicellular populations.
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@article {pmid39853129,
year = {2025},
author = {Espinoza Miranda, SS and Abbaszade, G and Hess, WR and Drescher, K and Saliba, A-E and Zaburdaev, V and Chai, L and Dreisewerd, K and Grünberger, A and Westendorf, C and Müller, S and Mascher, T},
title = {Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.},
journal = {Microbiology and molecular biology reviews : MMBR},
volume = {},
number = {},
pages = {e0013824},
doi = {10.1128/mmbr.00138-24},
pmid = {39853129},
issn = {1098-5557},
abstract = {SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole. During colony differentiation, an almost infinite number of ecological and physiological population-forming forces are at work, creating complex, intricate colony structures with divergent functions. Understanding the assembly and dynamics of such populations requires resolving individual cells or cell groups within such macroscopic structures. Addressing how each cell contributes to the collective action requires pushing the resolution boundaries of key technologies that will be presented in this review. In particular, single-cell techniques provide powerful tools for studying bacterial multicellularity with unprecedented spatial and temporal resolution. These advancements include novel microscopic techniques, mass spectrometry imaging, flow cytometry, spatial transcriptomics, single-bacteria RNA sequencing, and the integration of spatiotemporal transcriptomics with microscopy, alongside advanced microfluidic cultivation systems. This review encourages exploring the synergistic potential of the new technologies in the study of bacterial multicellularity, with a particular focus on individuals in differentiated bacterial biofilms (colonies). It highlights how resolving population structures at the single-cell level and understanding their respective functions can elucidate the overarching functions of bacterial multicellular populations.},
}
RevDate: 2025-01-24
T cell population size control by coronin 1 uncovered: from a spot identified by two-dimensional gel electrophoresis to quantitative proteomics.
Expert review of proteomics [Epub ahead of print].
INTRODUCTION: Recent work identified members of the evolutionarily conserved coronin protein family as key regulators of cell population size. This work originated ~25 years ago through the identification, by two-dimensional gel electrophoresis, of coronin 1 as a host protein involved in the virulence of Mycobacterium tuberculosis. We here describe the journey from a spot on a 2D gel to the recent realization that coronin proteins represent key controllers of eukaryotic cell population sizes, using ever more sophisticated proteomic techniques.
AREAS COVERED: We discuss the value of 'old school' proteomics using relatively simple and cost-effective technologies that allowed to gain insights into subcellular proteomes and describe how label-free quantitative (phospho)proteomics using mass spectrometry allowed to disentangle the role for coronin 1 in eukaryotic cell population size control. Finally, we mention potential implications of coronin-mediated cell population size control for health and disease.
EXPERT OPINION: Proteome analysis has been revolutionized by the advent of modern-day mass spectrometers and is indispensable for a better understanding of biology. Here, we discuss how careful dissection of physio-pathological processes by a combination of proteomics, genomics, biochemistry and cell biology may allow to zoom in on the unexplored, thereby possibly tackling hitherto unasked questions and defining novel mechanisms.
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@article {pmid39849824,
year = {2025},
author = {Ndinyanka, TF and Buczak, K and Schmidt, A and Pieters, J},
title = {T cell population size control by coronin 1 uncovered: from a spot identified by two-dimensional gel electrophoresis to quantitative proteomics.},
journal = {Expert review of proteomics},
volume = {},
number = {},
pages = {},
doi = {10.1080/14789450.2025.2450812},
pmid = {39849824},
issn = {1744-8387},
abstract = {INTRODUCTION: Recent work identified members of the evolutionarily conserved coronin protein family as key regulators of cell population size. This work originated ~25 years ago through the identification, by two-dimensional gel electrophoresis, of coronin 1 as a host protein involved in the virulence of Mycobacterium tuberculosis. We here describe the journey from a spot on a 2D gel to the recent realization that coronin proteins represent key controllers of eukaryotic cell population sizes, using ever more sophisticated proteomic techniques.
AREAS COVERED: We discuss the value of 'old school' proteomics using relatively simple and cost-effective technologies that allowed to gain insights into subcellular proteomes and describe how label-free quantitative (phospho)proteomics using mass spectrometry allowed to disentangle the role for coronin 1 in eukaryotic cell population size control. Finally, we mention potential implications of coronin-mediated cell population size control for health and disease.
EXPERT OPINION: Proteome analysis has been revolutionized by the advent of modern-day mass spectrometers and is indispensable for a better understanding of biology. Here, we discuss how careful dissection of physio-pathological processes by a combination of proteomics, genomics, biochemistry and cell biology may allow to zoom in on the unexplored, thereby possibly tackling hitherto unasked questions and defining novel mechanisms.},
}
RevDate: 2025-01-23
CmpDate: 2025-01-23
Regulation and function of a polarly localized lignin barrier in the exodermis.
Nature plants, 11(1):118-130.
Multicellular organisms control environmental interactions through specialized barriers in specific cell types. A conserved barrier in plant roots is the endodermal Casparian strip (CS), a ring-like structure made of polymerized lignin that seals the endodermal apoplastic space. Most angiosperms have another root cell type, the exodermis, that is reported to form a barrier. Our understanding of exodermal developmental and molecular regulation and function is limited as this cell type is absent from Arabidopsis thaliana. We demonstrate that in tomato (Solanum lycopersicum), the exodermis does not form a CS. Instead, it forms a polar lignin cap (PLC) with equivalent barrier function to the endodermal CS but distinct genetic control. Repression of the exodermal PLC in inner cortical layers is conferred by the SlSCZ and SlEXO1 transcription factors, and these two factors genetically interact to control its polar deposition. Several target genes that act downstream of SlSCZ and SlEXO1 in the exodermis are identified. Although the exodermis and endodermis produce barriers that restrict mineral ion uptake, the exodermal PLC is unable to fully compensate for the lack of a CS. The presence of distinct lignin structures acting as apoplastic barriers has exciting implications for a root's response to abiotic and biotic stimuli.
Additional Links: PMID-39623209
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@article {pmid39623209,
year = {2025},
author = {Manzano, C and Morimoto, KW and Shaar-Moshe, L and Mason, GA and Cantó-Pastor, A and Gouran, M and De Bellis, D and Ursache, R and Kajala, K and Sinha, N and Bailey-Serres, J and Geldner, N and Del Pozo, JC and Brady, SM},
title = {Regulation and function of a polarly localized lignin barrier in the exodermis.},
journal = {Nature plants},
volume = {11},
number = {1},
pages = {118-130},
pmid = {39623209},
issn = {2055-0278},
support = {HHMI 55108506//Howard Hughes Medical Institute (HHMI)/ ; 55108506//Howard Hughes Medical Institute (HHMI)/ ; NSF 2118017//National Science Foundation (NSF)/ ; PGRP IOS-211980//National Science Foundation (NSF)/ ; PGRP IOS-1856749//National Science Foundation (NSF)/ ; PRFB IOS-1907008//National Science Foundation (NSF)/ ; 655406//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 700057//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; FI-570-2018//United States - Israel Binational Agricultural Research and Development Fund (BARD)/ ; RGP0067/2021//Human Frontier Science Program (HFSP)/ ; Long-term Fellowship ALTF 1046-2015//European Molecular Biology Organization (EMBO)/ ; },
mesh = {*Lignin/metabolism ; *Solanum lycopersicum/genetics/metabolism/growth & development/physiology ; *Gene Expression Regulation, Plant ; *Plant Roots/metabolism/growth & development/genetics ; Plant Proteins/metabolism/genetics ; Transcription Factors/metabolism/genetics ; },
abstract = {Multicellular organisms control environmental interactions through specialized barriers in specific cell types. A conserved barrier in plant roots is the endodermal Casparian strip (CS), a ring-like structure made of polymerized lignin that seals the endodermal apoplastic space. Most angiosperms have another root cell type, the exodermis, that is reported to form a barrier. Our understanding of exodermal developmental and molecular regulation and function is limited as this cell type is absent from Arabidopsis thaliana. We demonstrate that in tomato (Solanum lycopersicum), the exodermis does not form a CS. Instead, it forms a polar lignin cap (PLC) with equivalent barrier function to the endodermal CS but distinct genetic control. Repression of the exodermal PLC in inner cortical layers is conferred by the SlSCZ and SlEXO1 transcription factors, and these two factors genetically interact to control its polar deposition. Several target genes that act downstream of SlSCZ and SlEXO1 in the exodermis are identified. Although the exodermis and endodermis produce barriers that restrict mineral ion uptake, the exodermal PLC is unable to fully compensate for the lack of a CS. The presence of distinct lignin structures acting as apoplastic barriers has exciting implications for a root's response to abiotic and biotic stimuli.},
}
MeSH Terms:
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*Lignin/metabolism
*Solanum lycopersicum/genetics/metabolism/growth & development/physiology
*Gene Expression Regulation, Plant
*Plant Roots/metabolism/growth & development/genetics
Plant Proteins/metabolism/genetics
Transcription Factors/metabolism/genetics
RevDate: 2025-01-21
CmpDate: 2025-01-21
Epithelia Are Scaffolds for Electricity-Dependent Molecular Interactions.
Reviews of physiology, biochemistry and pharmacology, 187:47-52.
Once multicellularity was thriving, a key development involved the emergence of epithelial layers that separated "inside" from "outside". Most epithelia then generate their own transepithelial electrical signals. So electrical forces were instrumental in the development of epithelial tissues, which themselves generate further electrical signals. Epithelia also developed extracellular basement membranes which act as spatially diverse scaffolds to organize multiple molecular interactions, dependent on electrical forces.Epithelia and basement membranes were constructed using electrical forces and their evolution had electrophysiological consequences.
Additional Links: PMID-39838007
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@article {pmid39838007,
year = {2025},
author = {McCaig, CD},
title = {Epithelia Are Scaffolds for Electricity-Dependent Molecular Interactions.},
journal = {Reviews of physiology, biochemistry and pharmacology},
volume = {187},
number = {},
pages = {47-52},
pmid = {39838007},
issn = {0303-4240},
mesh = {Animals ; Epithelium/physiology/metabolism ; Humans ; *Basement Membrane/metabolism/physiology ; Electricity ; Epithelial Cells/metabolism ; Electrophysiological Phenomena ; },
abstract = {Once multicellularity was thriving, a key development involved the emergence of epithelial layers that separated "inside" from "outside". Most epithelia then generate their own transepithelial electrical signals. So electrical forces were instrumental in the development of epithelial tissues, which themselves generate further electrical signals. Epithelia also developed extracellular basement membranes which act as spatially diverse scaffolds to organize multiple molecular interactions, dependent on electrical forces.Epithelia and basement membranes were constructed using electrical forces and their evolution had electrophysiological consequences.},
}
MeSH Terms:
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Animals
Epithelium/physiology/metabolism
Humans
*Basement Membrane/metabolism/physiology
Electricity
Epithelial Cells/metabolism
Electrophysiological Phenomena
RevDate: 2025-01-21
CmpDate: 2025-01-21
Development of an inducible DNA barcoding system to understand lineage changes in Arabidopsis regeneration.
Developmental cell, 60(2):305-319.e5.
Plants demonstrate a high degree of developmental plasticity, capable of regenerating entire individuals from detached somatic tissues-a regenerative phenomenon rarely observed in metazoa. Consequently, elucidating the lineage relationship between somatic founder cells and descendant cells in regenerated plant organs has long been a pursuit. In this study, we developed and optimized both DNA barcode- and multi-fluorescence-based cell-lineage tracing toolsets, employing an inducible method to mark individual cells in Arabidopsis donor somatic tissues at the onset of regeneration. Utilizing these complementary methods, we scrutinized cell identities at the single-cell level and presented compelling evidence that all cells in the regenerated Arabidopsis plants, irrespective of their organ types, originated from a single progenitor cell in the donor somatic tissue. Our discovery suggests a single-cell passage directing the transition from multicellular donor tissue to regenerated plants, thereby creating opportunities for cell-cell competition during plant regeneration-a strategy for maximizing survival.
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@article {pmid39591964,
year = {2025},
author = {Lu, X and Zhang, Q and Wang, Z and Cheng, X and Yan, H and Cai, S and Zhang, H and Liu, Q},
title = {Development of an inducible DNA barcoding system to understand lineage changes in Arabidopsis regeneration.},
journal = {Developmental cell},
volume = {60},
number = {2},
pages = {305-319.e5},
doi = {10.1016/j.devcel.2024.10.023},
pmid = {39591964},
issn = {1878-1551},
mesh = {*Arabidopsis/genetics ; *Regeneration/genetics/physiology ; *DNA Barcoding, Taxonomic/methods ; *Cell Lineage/genetics ; },
abstract = {Plants demonstrate a high degree of developmental plasticity, capable of regenerating entire individuals from detached somatic tissues-a regenerative phenomenon rarely observed in metazoa. Consequently, elucidating the lineage relationship between somatic founder cells and descendant cells in regenerated plant organs has long been a pursuit. In this study, we developed and optimized both DNA barcode- and multi-fluorescence-based cell-lineage tracing toolsets, employing an inducible method to mark individual cells in Arabidopsis donor somatic tissues at the onset of regeneration. Utilizing these complementary methods, we scrutinized cell identities at the single-cell level and presented compelling evidence that all cells in the regenerated Arabidopsis plants, irrespective of their organ types, originated from a single progenitor cell in the donor somatic tissue. Our discovery suggests a single-cell passage directing the transition from multicellular donor tissue to regenerated plants, thereby creating opportunities for cell-cell competition during plant regeneration-a strategy for maximizing survival.},
}
MeSH Terms:
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*Arabidopsis/genetics
*Regeneration/genetics/physiology
*DNA Barcoding, Taxonomic/methods
*Cell Lineage/genetics
RevDate: 2025-01-20
CmpDate: 2025-01-21
Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3.
Genome biology, 26(1):11.
BACKGROUND: The DNA/H3K9 methylation and Polycomb-group proteins (PcG)-H3K27me3 silencing pathways have long been considered mutually exclusive and specific to transposable elements (TEs) and genes, respectively in mammals, plants, and fungi. However, H3K27me3 can be recruited to many TEs in the absence of DNA/H3K9 methylation machinery and sometimes also co-occur with DNA methylation.
RESULTS: In this study, we show that TEs can also be solely targeted and silenced by H3K27me3 in wild-type Arabidopsis plants. These H3K27me3-marked TEs not only comprise degenerate relics but also seemingly intact copies that display the epigenetic features of responsive PcG target genes as well as an active H3K27me3 regulation. We also show that H3K27me3 can be deposited on newly inserted transgenic TE sequences in a TE-specific manner indicating that silencing is determined in cis. Finally, a comparison of Arabidopsis natural accessions reveals the existence of a category of TEs-which we refer to as "bifrons"-that are marked by DNA methylation or H3K27me3 depending on the accession. This variation can be linked to intrinsic TE features and to trans-acting factors and reveals a change in epigenetic status across the TE lifespan.
CONCLUSIONS: Our study sheds light on an alternative mode of TE silencing associated with H3K27me3 instead of DNA methylation in flowering plants. It also suggests dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes.
Additional Links: PMID-39833858
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@article {pmid39833858,
year = {2025},
author = {Hure, V and Piron-Prunier, F and Yehouessi, T and Vitte, C and Kornienko, AE and Adam, G and Nordborg, M and Déléris, A},
title = {Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {11},
pmid = {39833858},
issn = {1474-760X},
mesh = {*Arabidopsis/genetics ; *DNA Transposable Elements ; *Histones/metabolism ; *Gene Silencing ; *DNA Methylation ; Gene Expression Regulation, Plant ; Arabidopsis Proteins/genetics/metabolism ; Epigenesis, Genetic ; Polycomb-Group Proteins/metabolism/genetics ; },
abstract = {BACKGROUND: The DNA/H3K9 methylation and Polycomb-group proteins (PcG)-H3K27me3 silencing pathways have long been considered mutually exclusive and specific to transposable elements (TEs) and genes, respectively in mammals, plants, and fungi. However, H3K27me3 can be recruited to many TEs in the absence of DNA/H3K9 methylation machinery and sometimes also co-occur with DNA methylation.
RESULTS: In this study, we show that TEs can also be solely targeted and silenced by H3K27me3 in wild-type Arabidopsis plants. These H3K27me3-marked TEs not only comprise degenerate relics but also seemingly intact copies that display the epigenetic features of responsive PcG target genes as well as an active H3K27me3 regulation. We also show that H3K27me3 can be deposited on newly inserted transgenic TE sequences in a TE-specific manner indicating that silencing is determined in cis. Finally, a comparison of Arabidopsis natural accessions reveals the existence of a category of TEs-which we refer to as "bifrons"-that are marked by DNA methylation or H3K27me3 depending on the accession. This variation can be linked to intrinsic TE features and to trans-acting factors and reveals a change in epigenetic status across the TE lifespan.
CONCLUSIONS: Our study sheds light on an alternative mode of TE silencing associated with H3K27me3 instead of DNA methylation in flowering plants. It also suggests dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes.},
}
MeSH Terms:
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hide MeSH Terms
*Arabidopsis/genetics
*DNA Transposable Elements
*Histones/metabolism
*Gene Silencing
*DNA Methylation
Gene Expression Regulation, Plant
Arabidopsis Proteins/genetics/metabolism
Epigenesis, Genetic
Polycomb-Group Proteins/metabolism/genetics
RevDate: 2025-01-15
CmpDate: 2025-01-15
Multi-modal comparison of molecular programs driving nurse cell death and clearance in Drosophila melanogaster oogenesis.
PLoS genetics, 21(1):e1011220.
The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally. Alternatively, stressors such as starvation can induce the death of nurse cells earlier in mid-oogenesis, manifesting apoptosis signatures, followed by their engulfment by epithelial follicle cells. To identify and contrast the molecular pathways underlying these morphologically and genetically distinct cell death paradigms, both mediated by follicle cells, we compared their genome-wide transcriptional, translational, and secretion profiles before and after differentiating to acquire a phagocytic capability, as well as during well-fed and nutrient-deprived conditions. By coupling the GAL4-UAS system to Translating Ribosome Affinity Purification (TRAP-seq) and proximity labeling (HRP-KDEL) followed by Liquid Chromatography tandem mass-spectrometry, we performed high-throughput screens to identify pathways selectively activated or repressed by follicle cells to employ nurse cell-clearance routines. We also integrated two publicly available single-cell RNAseq atlases of the Drosophila ovary to define the transcriptomic profiles of follicle cells. In this report, we describe the genes and major pathways identified in the screens and the striking consequences to Drosophila melanogaster oogenesis caused by RNAi perturbation of prioritized candidates. To our knowledge, our study is the first of its kind to comprehensively characterize two distinct apoptotic and non-apoptotic cell death paradigms in the same multi-cellular system. Beyond molecular differences in cell death, our investigation may also provide insights into how key systemic trade-offs are made between survival and reproduction when faced with physiological stress.
Additional Links: PMID-39752622
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@article {pmid39752622,
year = {2025},
author = {Bandyadka, S and Lebo, DPV and Mondragon, AA and Serizier, SB and Kwan, J and Peterson, JS and Chasse, AY and Jenkins, VK and Calikyan, A and Ortega, AJ and Campbell, JD and Emili, A and McCall, K},
title = {Multi-modal comparison of molecular programs driving nurse cell death and clearance in Drosophila melanogaster oogenesis.},
journal = {PLoS genetics},
volume = {21},
number = {1},
pages = {e1011220},
pmid = {39752622},
issn = {1553-7404},
mesh = {Animals ; *Drosophila melanogaster/genetics ; *Oogenesis/genetics ; Female ; *Apoptosis/genetics ; *Drosophila Proteins/genetics/metabolism ; Oocytes/metabolism ; Ovarian Follicle/metabolism/cytology ; Cell Death/genetics ; Phagocytosis/genetics ; },
abstract = {The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally. Alternatively, stressors such as starvation can induce the death of nurse cells earlier in mid-oogenesis, manifesting apoptosis signatures, followed by their engulfment by epithelial follicle cells. To identify and contrast the molecular pathways underlying these morphologically and genetically distinct cell death paradigms, both mediated by follicle cells, we compared their genome-wide transcriptional, translational, and secretion profiles before and after differentiating to acquire a phagocytic capability, as well as during well-fed and nutrient-deprived conditions. By coupling the GAL4-UAS system to Translating Ribosome Affinity Purification (TRAP-seq) and proximity labeling (HRP-KDEL) followed by Liquid Chromatography tandem mass-spectrometry, we performed high-throughput screens to identify pathways selectively activated or repressed by follicle cells to employ nurse cell-clearance routines. We also integrated two publicly available single-cell RNAseq atlases of the Drosophila ovary to define the transcriptomic profiles of follicle cells. In this report, we describe the genes and major pathways identified in the screens and the striking consequences to Drosophila melanogaster oogenesis caused by RNAi perturbation of prioritized candidates. To our knowledge, our study is the first of its kind to comprehensively characterize two distinct apoptotic and non-apoptotic cell death paradigms in the same multi-cellular system. Beyond molecular differences in cell death, our investigation may also provide insights into how key systemic trade-offs are made between survival and reproduction when faced with physiological stress.},
}
MeSH Terms:
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Animals
*Drosophila melanogaster/genetics
*Oogenesis/genetics
Female
*Apoptosis/genetics
*Drosophila Proteins/genetics/metabolism
Oocytes/metabolism
Ovarian Follicle/metabolism/cytology
Cell Death/genetics
Phagocytosis/genetics
RevDate: 2025-01-13
CmpDate: 2025-01-13
Cancer Prevalence across Vertebrates.
Cancer discovery, 15(1):227-244.
Cancer is pervasive across multicellular species, but what explains the differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades of tetrapods (amphibians, sauropsids, and mammals), we found that neoplasia and malignancy prevalence increases with adult mass (contrary to Peto's paradox) and somatic mutation rate but decreases with gestation time. The relationship between adult mass and malignancy prevalence was only apparent when we controlled for gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%), the black-footed penguin (<0.4%), ferrets (63%), and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Significance: Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records, we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes. See related commentary by Metzger, p. 14.
Additional Links: PMID-39445720
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PubMed:
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@article {pmid39445720,
year = {2025},
author = {Compton, ZT and Mellon, W and Harris, VK and Rupp, S and Mallo, D and Kapsetaki, SE and Wilmot, M and Kennington, R and Noble, K and Baciu, C and Ramirez, LN and Peraza, A and Martins, B and Sudhakar, S and Aksoy, S and Furukawa, G and Vincze, O and Giraudeau, M and Duke, EG and Spiro, S and Flach, E and Davidson, H and Li, CI and Zehnder, A and Graham, TA and Troan, BV and Harrison, TM and Tollis, M and Schiffman, JD and Aktipis, CA and Abegglen, LM and Maley, CC and Boddy, AM},
title = {Cancer Prevalence across Vertebrates.},
journal = {Cancer discovery},
volume = {15},
number = {1},
pages = {227-244},
doi = {10.1158/2159-8290.CD-24-0573},
pmid = {39445720},
issn = {2159-8290},
support = {P01 CA091955/CA/NCI NIH HHS/United States ; OTKA K143421//Agence Nationale de la Recherche (ANR)/ ; U54 CA217376/CA/NCI NIH HHS/United States ; ADHS18-198847//Arizona Biomedical Research Commission (ABRC)/ ; U2C CA233254/CA/NCI NIH HHS/United States ; //Hyundai Hope On Wheels (Hope On Wheels)/ ; BC132057//Congressionally Directed Medical Research Programs (CDMRP)/ ; R01 CA140657/CA/NCI NIH HHS/United States ; R21 CA257980/CA/NCI NIH HHS/United States ; T32 CA272303/CA/NCI NIH HHS/United States ; COVER ANR-23-CE02-0019//Agence Nationale de la Recherche (ANR)/ ; U54 CA217376/CA/NCI NIH HHS/United States ; T32 CA272303/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Neoplasms/epidemiology/genetics ; Prevalence ; *Vertebrates ; Humans ; },
abstract = {Cancer is pervasive across multicellular species, but what explains the differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades of tetrapods (amphibians, sauropsids, and mammals), we found that neoplasia and malignancy prevalence increases with adult mass (contrary to Peto's paradox) and somatic mutation rate but decreases with gestation time. The relationship between adult mass and malignancy prevalence was only apparent when we controlled for gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%), the black-footed penguin (<0.4%), ferrets (63%), and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Significance: Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records, we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes. See related commentary by Metzger, p. 14.},
}
MeSH Terms:
show MeSH Terms
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Animals
*Neoplasms/epidemiology/genetics
Prevalence
*Vertebrates
Humans
RevDate: 2025-01-09
CmpDate: 2025-01-09
Collective sperm movement in mammalian reproductive tracts.
Seminars in cell & developmental biology, 166:13-21.
Mammalian sperm cells travel from their origin in the male reproductive tract to fertilization in the female tract through a complex process driven by coordinated mechanical and biochemical mechanisms. Recent experimental and theoretical advances have illuminated the collective behaviors of sperm both in vivo and in vitro. However, our understanding of the underlying mechano-chemical processes remains incomplete. This review integrates current insights into sperm group movement, examining both immotile and motile states, which are essential for passive transport and active swimming through the reproductive tracts. We provide an overview of the current understanding of collective sperm movement, focusing on the experimental and theoretical mechanisms behind these behaviors. We also explore how sperm motility is regulated through the coordination of mechanical and chemical processes. Emerging evidence highlights the mechanosensitive properties of a sperm flagellum, suggesting that mechanical stimuli regulate flagellar beating at both individual and collective levels. This self-regulatory, mechano-chemical system reflects a broader principle observed in multicellular systems, offering a system-level insight into the regulation of motility and collective dynamics in biological systems.
Additional Links: PMID-39675229
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PubMed:
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@article {pmid39675229,
year = {2025},
author = {Hirashima, T and W P, S and Noda, T},
title = {Collective sperm movement in mammalian reproductive tracts.},
journal = {Seminars in cell & developmental biology},
volume = {166},
number = {},
pages = {13-21},
doi = {10.1016/j.semcdb.2024.12.002},
pmid = {39675229},
issn = {1096-3634},
mesh = {*Sperm Motility/physiology ; Animals ; Male ; Humans ; *Spermatozoa/physiology/metabolism ; Mammals ; Female ; },
abstract = {Mammalian sperm cells travel from their origin in the male reproductive tract to fertilization in the female tract through a complex process driven by coordinated mechanical and biochemical mechanisms. Recent experimental and theoretical advances have illuminated the collective behaviors of sperm both in vivo and in vitro. However, our understanding of the underlying mechano-chemical processes remains incomplete. This review integrates current insights into sperm group movement, examining both immotile and motile states, which are essential for passive transport and active swimming through the reproductive tracts. We provide an overview of the current understanding of collective sperm movement, focusing on the experimental and theoretical mechanisms behind these behaviors. We also explore how sperm motility is regulated through the coordination of mechanical and chemical processes. Emerging evidence highlights the mechanosensitive properties of a sperm flagellum, suggesting that mechanical stimuli regulate flagellar beating at both individual and collective levels. This self-regulatory, mechano-chemical system reflects a broader principle observed in multicellular systems, offering a system-level insight into the regulation of motility and collective dynamics in biological systems.},
}
MeSH Terms:
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*Sperm Motility/physiology
Animals
Male
Humans
*Spermatozoa/physiology/metabolism
Mammals
Female
RevDate: 2025-01-08
CmpDate: 2025-01-08
Electrical signaling and coordinated behavior in the closest relative of animals.
Science advances, 11(2):eadr7434.
The transition from simple to complex multicellularity involves division of labor and specialization of cell types. In animals, complex sensory-motor systems are primarily built around specialized cells of muscles and neurons, though the evolutionary origins of these and their integration remain unclear. Here, to investigate sensory-behavior coupling in the closest relatives of animals, we established a line of the choanoflagellate, Salpingoeca rosetta, which stably expresses the calcium indicator RGECO1. Using this, we identify a previously unknown cellular behavior associated with electrical signaling, in which ciliary arrest is coupled with apical-basal contraction of the cell. This behavior and the associated calcium transients are synchronized in the multicellular state and result in coordinated ciliary arrest and colony-wide contraction, suggesting that information is spread among the cells. Our work reveals fundamental insights into how choanoflagellates sense and respond to their environment and enhances our understanding of the integration of cellular and organism-wide behavior in the closest protistan relatives of animals.
Additional Links: PMID-39772683
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@article {pmid39772683,
year = {2025},
author = {Colgren, J and Burkhardt, P},
title = {Electrical signaling and coordinated behavior in the closest relative of animals.},
journal = {Science advances},
volume = {11},
number = {2},
pages = {eadr7434},
doi = {10.1126/sciadv.adr7434},
pmid = {39772683},
issn = {2375-2548},
mesh = {*Choanoflagellata/physiology ; Animals ; Calcium/metabolism ; Cilia/physiology/metabolism ; Signal Transduction ; },
abstract = {The transition from simple to complex multicellularity involves division of labor and specialization of cell types. In animals, complex sensory-motor systems are primarily built around specialized cells of muscles and neurons, though the evolutionary origins of these and their integration remain unclear. Here, to investigate sensory-behavior coupling in the closest relatives of animals, we established a line of the choanoflagellate, Salpingoeca rosetta, which stably expresses the calcium indicator RGECO1. Using this, we identify a previously unknown cellular behavior associated with electrical signaling, in which ciliary arrest is coupled with apical-basal contraction of the cell. This behavior and the associated calcium transients are synchronized in the multicellular state and result in coordinated ciliary arrest and colony-wide contraction, suggesting that information is spread among the cells. Our work reveals fundamental insights into how choanoflagellates sense and respond to their environment and enhances our understanding of the integration of cellular and organism-wide behavior in the closest protistan relatives of animals.},
}
MeSH Terms:
show MeSH Terms
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*Choanoflagellata/physiology
Animals
Calcium/metabolism
Cilia/physiology/metabolism
Signal Transduction
RevDate: 2025-01-08
CmpDate: 2025-01-08
A mechanistic framework for complex microbe-host symbioses.
Trends in microbiology, 33(1):96-111.
Virtually all multicellular organisms on Earth live in symbiotic associations with complex microbial communities: the microbiome. This ancient relationship is of fundamental importance for both the host and the microbiome. Recently, the analyses of numerous microbiomes have revealed an incredible diversity and complexity of symbionts, with different mechanisms identified as potential drivers of this diversity. However, the interplay of ecological and evolutionary forces generating these complex associations is still poorly understood. Here we explore and summarise the suite of ecological and evolutionary mechanisms identified as relevant to different aspects of microbiome complexity and diversity. We argue that microbiome assembly is a dynamic product of ecology and evolution at various spatio-temporal scales. We propose a theoretical framework to classify mechanisms and build mechanistic host-microbiome models to link them to empirical patterns. We develop a cohesive foundation for the theoretical understanding of the combined effects of ecology and evolution on the assembly of complex symbioses.
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@article {pmid39242229,
year = {2025},
author = {Araujo, G and Montoya, JM and Thomas, T and Webster, NS and Lurgi, M},
title = {A mechanistic framework for complex microbe-host symbioses.},
journal = {Trends in microbiology},
volume = {33},
number = {1},
pages = {96-111},
doi = {10.1016/j.tim.2024.08.002},
pmid = {39242229},
issn = {1878-4380},
mesh = {*Symbiosis ; *Microbiota/physiology ; *Host Microbial Interactions/physiology ; *Biological Evolution ; Animals ; Humans ; Bacteria/genetics/classification ; Biodiversity ; Models, Biological ; },
abstract = {Virtually all multicellular organisms on Earth live in symbiotic associations with complex microbial communities: the microbiome. This ancient relationship is of fundamental importance for both the host and the microbiome. Recently, the analyses of numerous microbiomes have revealed an incredible diversity and complexity of symbionts, with different mechanisms identified as potential drivers of this diversity. However, the interplay of ecological and evolutionary forces generating these complex associations is still poorly understood. Here we explore and summarise the suite of ecological and evolutionary mechanisms identified as relevant to different aspects of microbiome complexity and diversity. We argue that microbiome assembly is a dynamic product of ecology and evolution at various spatio-temporal scales. We propose a theoretical framework to classify mechanisms and build mechanistic host-microbiome models to link them to empirical patterns. We develop a cohesive foundation for the theoretical understanding of the combined effects of ecology and evolution on the assembly of complex symbioses.},
}
MeSH Terms:
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*Symbiosis
*Microbiota/physiology
*Host Microbial Interactions/physiology
*Biological Evolution
Animals
Humans
Bacteria/genetics/classification
Biodiversity
Models, Biological
RevDate: 2025-01-07
Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.
bioRxiv : the preprint server for biology pii:2024.12.22.629997.
Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence. Further, the model predicts intrinsic bending direction in 3D space. Using this tool, we aimed to probe mechanical selection - that is, the evolutionary selection of DNA sequence based on its mechanical properties - in diverse circumstances. First, we found that the intrinsic bend direction of DNA sequences correlated with the observed bending in known protein-DNA complex structures, suggesting that many proteins co-evolved with their DNA partners to capture DNA in its intrinsically preferred bent conformation. We then applied our model to large-scale yeast population genetics data and showed that centromere DNA element II, whose consensus sequence is unknown, leaving its sequence-specific role unclear, is under mechanical selection to increase the stability of inner-kinetochore structure and to facilitate centromeric histone recruitment. Finally, in silico evolution under strong mechanical selection discovered hallucinated sequences with cyclizability values so extreme that they required experimental validation, yet, found in nature in the densely packed mitochondrial(mt) DNA of Namystynia karyoxenos , an ocean-dwelling protist with extreme mitochondrial gene fragmentation. The need to transmit an extraordinarily large amount of mtDNA, estimated to be > 600 Mb, in combination with the absence of mtDNA compaction proteins may have pushed mechanical selection to the extreme. Similarly extreme DNA mechanics are observed in bird microchromosomes, although the functional consequence is not yet clear. The discovery of eccentric DNA mechanics in unrelated unicellular and multicellular eukaryotes suggests that we can predict extreme natural biology which can arise through strong selection. Our methods offer a way to study the biological functions of DNA mechanics in any genome and to engineer DNA sequences with desired mechanical properties.
Additional Links: PMID-39763889
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@article {pmid39763889,
year = {2024},
author = {Park, J and Prokopchuk, G and Popchock, AR and Hao, J and Liao, TW and Yan, S and Hedman, DJ and Larson, JD and Walther, BK and Becker, NA and Basu, A and Maher, LJ and Wheeler, RJ and Asbury, CL and Biggins, S and Lukeš, J and Ha, T},
title = {Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.12.22.629997},
pmid = {39763889},
issn = {2692-8205},
abstract = {Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence. Further, the model predicts intrinsic bending direction in 3D space. Using this tool, we aimed to probe mechanical selection - that is, the evolutionary selection of DNA sequence based on its mechanical properties - in diverse circumstances. First, we found that the intrinsic bend direction of DNA sequences correlated with the observed bending in known protein-DNA complex structures, suggesting that many proteins co-evolved with their DNA partners to capture DNA in its intrinsically preferred bent conformation. We then applied our model to large-scale yeast population genetics data and showed that centromere DNA element II, whose consensus sequence is unknown, leaving its sequence-specific role unclear, is under mechanical selection to increase the stability of inner-kinetochore structure and to facilitate centromeric histone recruitment. Finally, in silico evolution under strong mechanical selection discovered hallucinated sequences with cyclizability values so extreme that they required experimental validation, yet, found in nature in the densely packed mitochondrial(mt) DNA of Namystynia karyoxenos , an ocean-dwelling protist with extreme mitochondrial gene fragmentation. The need to transmit an extraordinarily large amount of mtDNA, estimated to be > 600 Mb, in combination with the absence of mtDNA compaction proteins may have pushed mechanical selection to the extreme. Similarly extreme DNA mechanics are observed in bird microchromosomes, although the functional consequence is not yet clear. The discovery of eccentric DNA mechanics in unrelated unicellular and multicellular eukaryotes suggests that we can predict extreme natural biology which can arise through strong selection. Our methods offer a way to study the biological functions of DNA mechanics in any genome and to engineer DNA sequences with desired mechanical properties.},
}
RevDate: 2025-01-07
CmpDate: 2025-01-07
Cell-autonomous adaptation: an overlooked avenue of adaptation in human evolution.
Trends in genetics : TIG, 41(1):12-22.
Adaptation to environmental conditions occurs over diverse evolutionary timescales. In multi-cellular organisms, adaptive traits are often studied in tissues/organs relevant to the environmental challenge. We argue for the importance of an underappreciated layer of evolutionary adaptation manifesting at the cellular level. Cell-autonomous adaptations (CAAs) are inherited traits that boost organismal fitness by enhancing individual cell function. For instance, the cell-autonomous enhancement of mitochondrial oxygen utilization in hypoxic environments differs from an optimized erythropoiesis response, which involves multiple tissues. We explore the breadth of CAAs across challenges and highlight their counterparts in unicellular organisms. Applying these insights, we mine selection signals in Andean highlanders, revealing novel candidate CAAs. The conservation of CAAs across species may reveal valuable insights into multi-cellular evolution.
Additional Links: PMID-39732540
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PubMed:
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@article {pmid39732540,
year = {2025},
author = {Golomb, R and Dahan, O and Dahary, D and Pilpel, Y},
title = {Cell-autonomous adaptation: an overlooked avenue of adaptation in human evolution.},
journal = {Trends in genetics : TIG},
volume = {41},
number = {1},
pages = {12-22},
doi = {10.1016/j.tig.2024.10.009},
pmid = {39732540},
issn = {0168-9525},
mesh = {Humans ; *Adaptation, Physiological/genetics ; *Biological Evolution ; Mitochondria/genetics/metabolism ; Selection, Genetic/genetics ; Animals ; Evolution, Molecular ; },
abstract = {Adaptation to environmental conditions occurs over diverse evolutionary timescales. In multi-cellular organisms, adaptive traits are often studied in tissues/organs relevant to the environmental challenge. We argue for the importance of an underappreciated layer of evolutionary adaptation manifesting at the cellular level. Cell-autonomous adaptations (CAAs) are inherited traits that boost organismal fitness by enhancing individual cell function. For instance, the cell-autonomous enhancement of mitochondrial oxygen utilization in hypoxic environments differs from an optimized erythropoiesis response, which involves multiple tissues. We explore the breadth of CAAs across challenges and highlight their counterparts in unicellular organisms. Applying these insights, we mine selection signals in Andean highlanders, revealing novel candidate CAAs. The conservation of CAAs across species may reveal valuable insights into multi-cellular evolution.},
}
MeSH Terms:
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Humans
*Adaptation, Physiological/genetics
*Biological Evolution
Mitochondria/genetics/metabolism
Selection, Genetic/genetics
Animals
Evolution, Molecular
RevDate: 2025-01-06
CmpDate: 2025-01-06
Modeling of skeletal development and diseases using human pluripotent stem cells.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 40(1):5-19.
Human skeletal elements are formed from distinct origins at distinct positions of the embryo. For example, the neural crest produces the facial bones, the paraxial mesoderm produces the axial skeleton, and the lateral plate mesoderm produces the appendicular skeleton. During skeletal development, different combinations of signaling pathways are coordinated from distinct origins during the sequential developmental stages. Models for human skeletal development have been established using human pluripotent stem cells (hPSCs) and by exploiting our understanding of skeletal development. Stepwise protocols for generating skeletal cells from different origins have been designed to mimic developmental trails. Recently, organoid methods have allowed the multicellular organization of skeletal cell types to recapitulate complicated skeletal development and metabolism. Similarly, several genetic diseases of the skeleton have been modeled using patient-derived induced pluripotent stem cells and genome-editing technologies. Model-based drug screening is a powerful tool for identifying drug candidates. This review briefly summarizes our current understanding of the embryonic development of skeletal tissues and introduces the current state-of-the-art hPSC methods for recapitulating skeletal development, metabolism, and diseases. We also discuss the current limitations and future perspectives for applications of the hPSC-based modeling system in precision medicine in this research field.
Additional Links: PMID-39498496
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@article {pmid39498496,
year = {2024},
author = {Hojo, H and Tani, S and Ohba, S},
title = {Modeling of skeletal development and diseases using human pluripotent stem cells.},
journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research},
volume = {40},
number = {1},
pages = {5-19},
pmid = {39498496},
issn = {1523-4681},
support = {20H03885//Japan Society for the Promotion of Science/ ; //Rising Star Award from American Society for Bone and Mineral Research/ ; JP21bm0704071//Japan Agency for Medical Research and Development/ ; JPMJFR225N//Japan Science and Technology Agency/ ; JPMJER2401//JST ERATO program/ ; },
mesh = {Humans ; *Pluripotent Stem Cells/metabolism/cytology ; *Models, Biological ; *Bone Development ; Bone Diseases/pathology ; Bone and Bones/metabolism/embryology ; Animals ; },
abstract = {Human skeletal elements are formed from distinct origins at distinct positions of the embryo. For example, the neural crest produces the facial bones, the paraxial mesoderm produces the axial skeleton, and the lateral plate mesoderm produces the appendicular skeleton. During skeletal development, different combinations of signaling pathways are coordinated from distinct origins during the sequential developmental stages. Models for human skeletal development have been established using human pluripotent stem cells (hPSCs) and by exploiting our understanding of skeletal development. Stepwise protocols for generating skeletal cells from different origins have been designed to mimic developmental trails. Recently, organoid methods have allowed the multicellular organization of skeletal cell types to recapitulate complicated skeletal development and metabolism. Similarly, several genetic diseases of the skeleton have been modeled using patient-derived induced pluripotent stem cells and genome-editing technologies. Model-based drug screening is a powerful tool for identifying drug candidates. This review briefly summarizes our current understanding of the embryonic development of skeletal tissues and introduces the current state-of-the-art hPSC methods for recapitulating skeletal development, metabolism, and diseases. We also discuss the current limitations and future perspectives for applications of the hPSC-based modeling system in precision medicine in this research field.},
}
MeSH Terms:
show MeSH Terms
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Humans
*Pluripotent Stem Cells/metabolism/cytology
*Models, Biological
*Bone Development
Bone Diseases/pathology
Bone and Bones/metabolism/embryology
Animals
RevDate: 2025-01-06
CmpDate: 2025-01-06
Development of ectodermal and endodermal taste buds.
Developmental biology, 518:20-27.
The sense of taste is mediated primarily by taste buds on the tongue. These multicellular sensory organs are induced, patterned and become innervated during embryogenesis such that a functional taste system is present at birth when animals begin to feed. While taste buds have been considered ectodermal appendages, this is only partly accurate as only fungiform taste buds in the anterior tongue arise from the ectoderm. Taste buds found in the posterior tongue actually derive from endoderm. Nonetheless, both anterior and posterior buds are functionally similar, despite their disparate embryonic origins. In this review, I compare the development of ectodermal vs endodermal taste buds, highlighting the many differences in the cellular and molecular genetic mechanisms governing their formation.
Additional Links: PMID-39486632
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@article {pmid39486632,
year = {2025},
author = {Barlow, LA},
title = {Development of ectodermal and endodermal taste buds.},
journal = {Developmental biology},
volume = {518},
number = {},
pages = {20-27},
pmid = {39486632},
issn = {1095-564X},
mesh = {Animals ; *Taste Buds/embryology ; *Ectoderm/embryology/metabolism ; *Endoderm/embryology ; Tongue/embryology ; Humans ; Gene Expression Regulation, Developmental ; },
abstract = {The sense of taste is mediated primarily by taste buds on the tongue. These multicellular sensory organs are induced, patterned and become innervated during embryogenesis such that a functional taste system is present at birth when animals begin to feed. While taste buds have been considered ectodermal appendages, this is only partly accurate as only fungiform taste buds in the anterior tongue arise from the ectoderm. Taste buds found in the posterior tongue actually derive from endoderm. Nonetheless, both anterior and posterior buds are functionally similar, despite their disparate embryonic origins. In this review, I compare the development of ectodermal vs endodermal taste buds, highlighting the many differences in the cellular and molecular genetic mechanisms governing their formation.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Taste Buds/embryology
*Ectoderm/embryology/metabolism
*Endoderm/embryology
Tongue/embryology
Humans
Gene Expression Regulation, Developmental
RevDate: 2024-12-31
CmpDate: 2024-12-31
Open problems in synthetic multicellularity.
NPJ systems biology and applications, 10(1):151.
Multicellularity is one of the major evolutionary transitions, and its rise provided the ingredients for the emergence of a biosphere inhabited by complex organisms. Over the last decades, the potential for bioengineering multicellular systems has been instrumental in interrogating nature and exploring novel paths to regeneration, disease, cognition, and behaviour. Here, we provide a list of open problems that encapsulate many of the ongoing and future challenges in the field and suggest conceptual approaches that may facilitate progress.
Additional Links: PMID-39741147
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@article {pmid39741147,
year = {2024},
author = {Solé, R and Conde-Pueyo, N and Pla-Mauri, J and Garcia-Ojalvo, J and Montserrat, N and Levin, M},
title = {Open problems in synthetic multicellularity.},
journal = {NPJ systems biology and applications},
volume = {10},
number = {1},
pages = {151},
pmid = {39741147},
issn = {2056-7189},
support = {ERCCoG-2020 101002478 ENGINORG//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; Grant 62212//John Templeton Foundation (JTF)/ ; },
mesh = {*Synthetic Biology/methods ; Humans ; Models, Biological ; Bioengineering/methods ; Biological Evolution ; Animals ; Systems Biology/methods ; },
abstract = {Multicellularity is one of the major evolutionary transitions, and its rise provided the ingredients for the emergence of a biosphere inhabited by complex organisms. Over the last decades, the potential for bioengineering multicellular systems has been instrumental in interrogating nature and exploring novel paths to regeneration, disease, cognition, and behaviour. Here, we provide a list of open problems that encapsulate many of the ongoing and future challenges in the field and suggest conceptual approaches that may facilitate progress.},
}
MeSH Terms:
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*Synthetic Biology/methods
Humans
Models, Biological
Bioengineering/methods
Biological Evolution
Animals
Systems Biology/methods
RevDate: 2024-12-23
Protein family FAM241 in human and mouse.
Mammalian genome : official journal of the International Mammalian Genome Society [Epub ahead of print].
FAM241B was isolated in a genome-wide inactivation screen for generation of enlarged lysosomes. FAM241B and FAM241A comprise protein family FAM241 encoding proteins of 121 and 132 amino acid residues, respectively. The proteins exhibit 25% amino acid sequence identity and contain a domain of unknown function (DUF4605; pfam15378) that is conserved from primitive multicellular eukaryotes through vertebrates. Phylogenetic comparison indicates that duplication of the ancestral FAM241B gene occurred prior to the origin of fish. FAM241B has been deleted from the avian lineage. Fam241a and Fam241b are widely expressed in mouse tissues. Experimental knockout of mouse Fam241a, Fam241b, and the double knockout, did not generate a visible phenotype. Knockout of Fam241A and Fam241B did not exacerbate the phenotype of FIG4 null mice. RNAseq of brain RNA from double knockout mice detected reduced expression of several genes including Arke1e1 and RnaseL. The human variant p.Val115Gly in FAM241B was identified in a patient with developmental delay. Lysosome morphology in patient-derived fibroblasts was normal. In previous studies, FAM241A and FAM241B appeared to co-localize with proteins of the endoplasmic reticulum. The molecular function of this ancient protein family remains to be determined.
Additional Links: PMID-39715844
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@article {pmid39715844,
year = {2024},
author = {Doctrove, Q and Park, Y and Calame, DG and Kitzman, J and Lenk, GM and Meisler, MH},
title = {Protein family FAM241 in human and mouse.},
journal = {Mammalian genome : official journal of the International Mammalian Genome Society},
volume = {},
number = {},
pages = {},
pmid = {39715844},
issn = {1432-1777},
support = {R01 GM24872/NH/NIH HHS/United States ; 873841//Muscular Dystrophy Association/ ; K12NS098482/NS/NINDS NIH HHS/United States ; },
abstract = {FAM241B was isolated in a genome-wide inactivation screen for generation of enlarged lysosomes. FAM241B and FAM241A comprise protein family FAM241 encoding proteins of 121 and 132 amino acid residues, respectively. The proteins exhibit 25% amino acid sequence identity and contain a domain of unknown function (DUF4605; pfam15378) that is conserved from primitive multicellular eukaryotes through vertebrates. Phylogenetic comparison indicates that duplication of the ancestral FAM241B gene occurred prior to the origin of fish. FAM241B has been deleted from the avian lineage. Fam241a and Fam241b are widely expressed in mouse tissues. Experimental knockout of mouse Fam241a, Fam241b, and the double knockout, did not generate a visible phenotype. Knockout of Fam241A and Fam241B did not exacerbate the phenotype of FIG4 null mice. RNAseq of brain RNA from double knockout mice detected reduced expression of several genes including Arke1e1 and RnaseL. The human variant p.Val115Gly in FAM241B was identified in a patient with developmental delay. Lysosome morphology in patient-derived fibroblasts was normal. In previous studies, FAM241A and FAM241B appeared to co-localize with proteins of the endoplasmic reticulum. The molecular function of this ancient protein family remains to be determined.},
}
RevDate: 2024-12-23
CmpDate: 2024-12-23
Epigenomic heterogeneity as a source of tumour evolution.
Nature reviews. Cancer, 25(1):7-26.
In the past decade, remarkable progress in cancer medicine has been achieved by the development of treatments that target DNA sequence variants. However, a purely genetic approach to treatment selection is hampered by the fact that diverse cell states can emerge from the same genotype. In multicellular organisms, cell-state heterogeneity is driven by epigenetic processes that regulate DNA-based functions such as transcription; disruption of these processes is a hallmark of cancer that enables the emergence of defective cell states. Advances in single-cell technologies have unlocked our ability to quantify the epigenomic heterogeneity of tumours and understand its mechanisms, thereby transforming our appreciation of how epigenomic changes drive cancer evolution. This Review explores the idea that epigenomic heterogeneity and plasticity act as a reservoir of cell states and therefore as a source of tumour evolution. Best practices to quantify epigenomic heterogeneity and explore its various causes and consequences are discussed, including epigenomic reprogramming, stochastic changes and lasting memory. The design of new therapeutic approaches to restrict epigenomic heterogeneity, with the long-term objective of limiting cancer development and progression, is also addressed.
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@article {pmid39414948,
year = {2025},
author = {Laisné, M and Lupien, M and Vallot, C},
title = {Epigenomic heterogeneity as a source of tumour evolution.},
journal = {Nature reviews. Cancer},
volume = {25},
number = {1},
pages = {7-26},
pmid = {39414948},
issn = {1474-1768},
mesh = {Humans ; *Neoplasms/genetics/pathology ; *Epigenesis, Genetic ; *Epigenomics ; *Genetic Heterogeneity ; Animals ; },
abstract = {In the past decade, remarkable progress in cancer medicine has been achieved by the development of treatments that target DNA sequence variants. However, a purely genetic approach to treatment selection is hampered by the fact that diverse cell states can emerge from the same genotype. In multicellular organisms, cell-state heterogeneity is driven by epigenetic processes that regulate DNA-based functions such as transcription; disruption of these processes is a hallmark of cancer that enables the emergence of defective cell states. Advances in single-cell technologies have unlocked our ability to quantify the epigenomic heterogeneity of tumours and understand its mechanisms, thereby transforming our appreciation of how epigenomic changes drive cancer evolution. This Review explores the idea that epigenomic heterogeneity and plasticity act as a reservoir of cell states and therefore as a source of tumour evolution. Best practices to quantify epigenomic heterogeneity and explore its various causes and consequences are discussed, including epigenomic reprogramming, stochastic changes and lasting memory. The design of new therapeutic approaches to restrict epigenomic heterogeneity, with the long-term objective of limiting cancer development and progression, is also addressed.},
}
MeSH Terms:
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Humans
*Neoplasms/genetics/pathology
*Epigenesis, Genetic
*Epigenomics
*Genetic Heterogeneity
Animals
RevDate: 2024-12-21
CmpDate: 2024-12-21
[Participation of Proteins of the CPSF Complex in Polyadenylation of Transcripts Read by RNA Polymerase III from SINEs].
Molekuliarnaia biologiia, 58(3):437-447.
SINEs are mobile genetic elements of multicellular eukaryotes that arose during evolution from various tRNAs, as well as from 5S rRNA and 7SL RNA. Like the genes of these RNAs, SINEs are transcribed by RNA polymerase III. The transcripts of some mammalian SINEs have the capability of AAUAAA-dependent polyadenylation, which is unique for transcript generated by RNA polymerase III. Despite a certain similarity with canonical polyadenylation of mRNAs (transcripts of RNA polymerase II), these processes apparently differ significantly. The purpose of this work is to evaluate how important for polyadenylation of SINE transcripts are proteins of the CPSF complex formed by mPSF and mCF subcomplexes which direct mRNA polyadenylation. In HeLa cells, siRNA knockdowns of the CPSF components were carried out, after which the cells were transfected with plasmid constructs containing SINEs. A decrease in polyadenylation of the SINE transcripts as a result of the knockdown of the proteins was evaluated by Northern-hybridization. It turned out that the CPSF components, such as Wdr33 and CPSF30, contributed to the polyadenylation of SINE transcriptions, while the knockdown of CPSF100, CPSF73, and symplekin did not reduce the polyadenylation of these transcripts. Wdr33 and CPSF30, along with the CPSF160 and Fip1 previously studied, are components of the subcomplex mPSF responsible for mRNA polyadenylation. Thus, the available data suggest the importance of all mPSF proteins for polyadenylation of SINE transcripts. At the same time, CPSF100, CPSF73, and symplekin, forming the subcomplex mCF, are responsible for the cleavage of pre-mRNA; therefore, their non-participation in the polyadenylation of SINE transcriptions seems quite natural.
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@article {pmid39707854,
year = {2024},
author = {Ustyantsev, IG and Borodulina, OR and Kramerov, DA},
title = {[Participation of Proteins of the CPSF Complex in Polyadenylation of Transcripts Read by RNA Polymerase III from SINEs].},
journal = {Molekuliarnaia biologiia},
volume = {58},
number = {3},
pages = {437-447},
pmid = {39707854},
issn = {0026-8984},
mesh = {Humans ; *Polyadenylation ; HeLa Cells ; *Cleavage And Polyadenylation Specificity Factor/metabolism/genetics ; *RNA Polymerase III/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; mRNA Cleavage and Polyadenylation Factors/metabolism/genetics ; Alu Elements/genetics ; Gene Knockdown Techniques ; Nuclear Proteins ; },
abstract = {SINEs are mobile genetic elements of multicellular eukaryotes that arose during evolution from various tRNAs, as well as from 5S rRNA and 7SL RNA. Like the genes of these RNAs, SINEs are transcribed by RNA polymerase III. The transcripts of some mammalian SINEs have the capability of AAUAAA-dependent polyadenylation, which is unique for transcript generated by RNA polymerase III. Despite a certain similarity with canonical polyadenylation of mRNAs (transcripts of RNA polymerase II), these processes apparently differ significantly. The purpose of this work is to evaluate how important for polyadenylation of SINE transcripts are proteins of the CPSF complex formed by mPSF and mCF subcomplexes which direct mRNA polyadenylation. In HeLa cells, siRNA knockdowns of the CPSF components were carried out, after which the cells were transfected with plasmid constructs containing SINEs. A decrease in polyadenylation of the SINE transcripts as a result of the knockdown of the proteins was evaluated by Northern-hybridization. It turned out that the CPSF components, such as Wdr33 and CPSF30, contributed to the polyadenylation of SINE transcriptions, while the knockdown of CPSF100, CPSF73, and symplekin did not reduce the polyadenylation of these transcripts. Wdr33 and CPSF30, along with the CPSF160 and Fip1 previously studied, are components of the subcomplex mPSF responsible for mRNA polyadenylation. Thus, the available data suggest the importance of all mPSF proteins for polyadenylation of SINE transcripts. At the same time, CPSF100, CPSF73, and symplekin, forming the subcomplex mCF, are responsible for the cleavage of pre-mRNA; therefore, their non-participation in the polyadenylation of SINE transcriptions seems quite natural.},
}
MeSH Terms:
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Humans
*Polyadenylation
HeLa Cells
*Cleavage And Polyadenylation Specificity Factor/metabolism/genetics
*RNA Polymerase III/metabolism/genetics
*RNA, Messenger/genetics/metabolism
mRNA Cleavage and Polyadenylation Factors/metabolism/genetics
Alu Elements/genetics
Gene Knockdown Techniques
Nuclear Proteins
RevDate: 2024-12-21
CmpDate: 2024-12-21
Characterization of the Calmodulin-Like Protein Family in Chara braunii and their Conserved Interaction with the Calmodulin-Binding Transcription Activator Family.
Plant & cell physiology, 65(12):2040-2053.
Calcium sensor proteins play important roles by detecting changes in intracellular calcium and relaying that information onto downstream targets through protein-protein interaction. Very little is known about calcium sensors from plant species that predate land colonization and the evolution of embryophytes. Here, we examined the genome of the multicellular algae, Chara braunii, for orthologs to the evolutionarily conserved calcium sensor calmodulin (CaM) and for CaM-like (CML) proteins. We identified one CaM and eight CML isoforms that range in size from 16.4 to 21.3 kDa and are predicted to have between two to four calcium-binding (EF-hand) domains. Using recombinant protein, we tested whether CbCaM and CbCML1-CbCML7 possess biochemical properties of typical calcium sensors. CbCaM and the CbCMLs all displayed high-affinity calcium binding with estimated global KD,app values in the physiological µM range. In response to calcium binding, CbCaM and the CbCMLs exhibited varying degrees of increase in exposed hydrophobicity, suggesting that different calcium-induced conformational changes occur among isoforms. We found many examples of putative CaM targets encoded in the C. braunii genome and explored the ability of CbCaM and CbCMLs to interact in planta with a representative putative target, a C. braunii CaM-binding transcription factor (CbCAMTA1). CbCaM, CbCML2 and CbCML4 each associated with the C-terminal region of CbCAMTA1. Collectively, our data support the hypothesis that complex calcium signaling and sensing networks involving CaM and CMLs evolved early in the green lineage. Similarly, it seems likely that calcium-mediated regulation of transcription occurs in C. braunii via CAMTAs and is an ancient trait predating embryophytic emergence.
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@article {pmid39460541,
year = {2024},
author = {Symonds, K and Wali, U and Duff, L and Snedden, WA},
title = {Characterization of the Calmodulin-Like Protein Family in Chara braunii and their Conserved Interaction with the Calmodulin-Binding Transcription Activator Family.},
journal = {Plant & cell physiology},
volume = {65},
number = {12},
pages = {2040-2053},
doi = {10.1093/pcp/pcae127},
pmid = {39460541},
issn = {1471-9053},
support = {RGPIN-2018-04928, RGPIN-2017-04551//Natural Sciences and Engineering Research Council of Canada/ ; },
mesh = {*Calmodulin/metabolism/genetics ; *Plant Proteins/metabolism/genetics ; *Calcium/metabolism ; *Chara/metabolism/genetics ; Phylogeny ; Amino Acid Sequence ; Protein Binding ; Calmodulin-Binding Proteins/metabolism/genetics ; Protein Isoforms/metabolism/genetics ; },
abstract = {Calcium sensor proteins play important roles by detecting changes in intracellular calcium and relaying that information onto downstream targets through protein-protein interaction. Very little is known about calcium sensors from plant species that predate land colonization and the evolution of embryophytes. Here, we examined the genome of the multicellular algae, Chara braunii, for orthologs to the evolutionarily conserved calcium sensor calmodulin (CaM) and for CaM-like (CML) proteins. We identified one CaM and eight CML isoforms that range in size from 16.4 to 21.3 kDa and are predicted to have between two to four calcium-binding (EF-hand) domains. Using recombinant protein, we tested whether CbCaM and CbCML1-CbCML7 possess biochemical properties of typical calcium sensors. CbCaM and the CbCMLs all displayed high-affinity calcium binding with estimated global KD,app values in the physiological µM range. In response to calcium binding, CbCaM and the CbCMLs exhibited varying degrees of increase in exposed hydrophobicity, suggesting that different calcium-induced conformational changes occur among isoforms. We found many examples of putative CaM targets encoded in the C. braunii genome and explored the ability of CbCaM and CbCMLs to interact in planta with a representative putative target, a C. braunii CaM-binding transcription factor (CbCAMTA1). CbCaM, CbCML2 and CbCML4 each associated with the C-terminal region of CbCAMTA1. Collectively, our data support the hypothesis that complex calcium signaling and sensing networks involving CaM and CMLs evolved early in the green lineage. Similarly, it seems likely that calcium-mediated regulation of transcription occurs in C. braunii via CAMTAs and is an ancient trait predating embryophytic emergence.},
}
MeSH Terms:
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*Calmodulin/metabolism/genetics
*Plant Proteins/metabolism/genetics
*Calcium/metabolism
*Chara/metabolism/genetics
Phylogeny
Amino Acid Sequence
Protein Binding
Calmodulin-Binding Proteins/metabolism/genetics
Protein Isoforms/metabolism/genetics
RevDate: 2024-12-20
CmpDate: 2024-12-20
Mechanical induction in metazoan development and evolution: from earliest multi-cellular organisms to modern animal embryos.
Nature communications, 15(1):10695.
The development and origin of animal body forms have long been intensely explored, from the analysis of morphological traits during antiquity to Newtonian mechanical conceptions of morphogenesis. Advent of molecular biology then focused most interests on the biochemical patterning and genetic regulation of embryonic development. Today, a view is arising of development of multicellular living forms as a phenomenon emerging from non-hierarchical, reciprocal mechanical and mechanotransductive interactions between biochemical patterning and biomechanical morphogenesis. Here we discuss the nature of these processes and put forward findings on how early biochemical and biomechanical patterning of metazoans may have emerged from a primitive behavioural mechanotransducive feeding response to marine environment which might have initiated the development of first animal multicellular organisms.
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@article {pmid39702750,
year = {2024},
author = {Nguyen, NM and Farge, E},
title = {Mechanical induction in metazoan development and evolution: from earliest multi-cellular organisms to modern animal embryos.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {10695},
pmid = {39702750},
issn = {2041-1723},
mesh = {Animals ; *Biological Evolution ; *Embryonic Development/genetics ; Biomechanical Phenomena ; Body Patterning ; Morphogenesis ; Embryo, Nonmammalian ; },
abstract = {The development and origin of animal body forms have long been intensely explored, from the analysis of morphological traits during antiquity to Newtonian mechanical conceptions of morphogenesis. Advent of molecular biology then focused most interests on the biochemical patterning and genetic regulation of embryonic development. Today, a view is arising of development of multicellular living forms as a phenomenon emerging from non-hierarchical, reciprocal mechanical and mechanotransductive interactions between biochemical patterning and biomechanical morphogenesis. Here we discuss the nature of these processes and put forward findings on how early biochemical and biomechanical patterning of metazoans may have emerged from a primitive behavioural mechanotransducive feeding response to marine environment which might have initiated the development of first animal multicellular organisms.},
}
MeSH Terms:
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Animals
*Biological Evolution
*Embryonic Development/genetics
Biomechanical Phenomena
Body Patterning
Morphogenesis
Embryo, Nonmammalian
RevDate: 2024-12-17
CmpDate: 2024-12-17
Form, function, and evolutionary origins of architectural symmetry in honey bee nests.
Current biology : CB, 34(24):5813-5821.e5.
Symmetry is pervasive across the tree of life,[1][,][2][,][3][,][4][,][5] and organisms (including humans) build symmetrical structures for reproduction, locomotion, or aesthetics.[6][,][7][,][8][,][9] Symmetry, however, does not necessarily span across levels of biological organization (e.g., symmetrical body plans often have asymmetric organs).[10] If and how symmetry exists in structures built by social insect collectives, where there is no blueprint or central organizer, remains an open question.[11] Here, we show that honey bees actively organize nest contents symmetrically on either side of their double-sided comb; 79% ± 7% of cell contents match their backside counterpart, creating a mirror image inside the nest. Experimentally restricting colonies to opposite sides of comb, we find that independent colonies will symmetrically mimic each other's nest organization. We then examine the mechanism by which independent colonies can indirectly coordinate nest symmetry, showing that 100% of colonies (n = 6) perfectly co-localize their brood nest with a randomly positioned heat source, indicating that heat drives nest site initiation and early brood production. Nest symmetry also has adaptive benefits: two-sided nests grow more quickly, rear more brood, and have a more stable thermal environment than one-sided nests do. Finally, examining the evolutionary origins, we show that symmetry persists in three-dimensional (3D) nests of Apis mellifera and across multiple Apis species, coinciding with the onset of double-sided combs, which made it possible to symmetrically stockpile nest contents. This work shows that, similar to molecular mechanisms that create symmetry in multicellular organisms, there are behavioral processes that create functional symmetry in the collective organization of animal architecture.
Additional Links: PMID-39515324
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@article {pmid39515324,
year = {2024},
author = {Smith, ML and Marting, PR and Bailey, CS and Chuttong, B and Maul, ER and Molinari, R and Prathibha, P and Rowe, EB and Spott, MR and Koger, B},
title = {Form, function, and evolutionary origins of architectural symmetry in honey bee nests.},
journal = {Current biology : CB},
volume = {34},
number = {24},
pages = {5813-5821.e5},
doi = {10.1016/j.cub.2024.10.022},
pmid = {39515324},
issn = {1879-0445},
mesh = {Animals ; Bees/physiology/anatomy & histology ; *Nesting Behavior ; *Biological Evolution ; },
abstract = {Symmetry is pervasive across the tree of life,[1][,][2][,][3][,][4][,][5] and organisms (including humans) build symmetrical structures for reproduction, locomotion, or aesthetics.[6][,][7][,][8][,][9] Symmetry, however, does not necessarily span across levels of biological organization (e.g., symmetrical body plans often have asymmetric organs).[10] If and how symmetry exists in structures built by social insect collectives, where there is no blueprint or central organizer, remains an open question.[11] Here, we show that honey bees actively organize nest contents symmetrically on either side of their double-sided comb; 79% ± 7% of cell contents match their backside counterpart, creating a mirror image inside the nest. Experimentally restricting colonies to opposite sides of comb, we find that independent colonies will symmetrically mimic each other's nest organization. We then examine the mechanism by which independent colonies can indirectly coordinate nest symmetry, showing that 100% of colonies (n = 6) perfectly co-localize their brood nest with a randomly positioned heat source, indicating that heat drives nest site initiation and early brood production. Nest symmetry also has adaptive benefits: two-sided nests grow more quickly, rear more brood, and have a more stable thermal environment than one-sided nests do. Finally, examining the evolutionary origins, we show that symmetry persists in three-dimensional (3D) nests of Apis mellifera and across multiple Apis species, coinciding with the onset of double-sided combs, which made it possible to symmetrically stockpile nest contents. This work shows that, similar to molecular mechanisms that create symmetry in multicellular organisms, there are behavioral processes that create functional symmetry in the collective organization of animal architecture.},
}
MeSH Terms:
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Animals
Bees/physiology/anatomy & histology
*Nesting Behavior
*Biological Evolution
RevDate: 2024-12-14
CmpDate: 2024-12-14
Survey for Activating Oncogenic Mutation Variants in Metazoan Germline Genes.
Journal of molecular evolution, 92(6):930-943.
Most cancers present with mutations or amplifications in distinctive tumor promoter genes that activate principal cell-signaling cascades promoting cell proliferation, dedifferentiation, cell survival, and replicative immortality. Somatic mutations found in this these driver proto-oncogenes invariably result in constitutive activation of the encoded protein. A salient feature of the activating mutations observed throughout many thousands of clinical tumor specimens reveals these driver missense mutations are recurrent and restricted to just one or very few codons of the entire gene, suggesting they have been positively selected during the course of tumor development. The purpose of this study is to investigate whether these characteristic oncogenic driver mutations are observed in the germline genes of any metazoan species. Six well-known tumor promoter genes were chosen for this survey including BRAF, KRAS, JAK2, PIK3CA, EGFR, and IDH1/2. The sites of all driver mutations were found to occur in highly conserved regions of each gene comparing protein sequences throughout diverse phyla of metazoan species. None of the oncogenic missense mutations were found in germlines of any species of current genome and protein databases. Despite many tumors readily selecting these somatic mutations, the conclusion drawn from this study is that these variants are negatively rejected if encountered as a germline mutation. While cancer expansion ensues from dysregulated growth elicited by these mutations, this effect is likely detrimental to embryonic development and/or survival of multicellular organisms. Although all oncogenic mutations considered here are gain-of-function where five of the six increase activity of the encoded proteins, clonal advancement promotes tumor growth by these genomic changes without conferring selection advantages benefiting the organism or species.
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@article {pmid39589477,
year = {2024},
author = {Krueger, KE},
title = {Survey for Activating Oncogenic Mutation Variants in Metazoan Germline Genes.},
journal = {Journal of molecular evolution},
volume = {92},
number = {6},
pages = {930-943},
pmid = {39589477},
issn = {1432-1432},
mesh = {Animals ; *Germ-Line Mutation/genetics ; Humans ; Neoplasms/genetics ; Oncogenes/genetics ; Mutation, Missense/genetics ; Germ Cells/metabolism ; },
abstract = {Most cancers present with mutations or amplifications in distinctive tumor promoter genes that activate principal cell-signaling cascades promoting cell proliferation, dedifferentiation, cell survival, and replicative immortality. Somatic mutations found in this these driver proto-oncogenes invariably result in constitutive activation of the encoded protein. A salient feature of the activating mutations observed throughout many thousands of clinical tumor specimens reveals these driver missense mutations are recurrent and restricted to just one or very few codons of the entire gene, suggesting they have been positively selected during the course of tumor development. The purpose of this study is to investigate whether these characteristic oncogenic driver mutations are observed in the germline genes of any metazoan species. Six well-known tumor promoter genes were chosen for this survey including BRAF, KRAS, JAK2, PIK3CA, EGFR, and IDH1/2. The sites of all driver mutations were found to occur in highly conserved regions of each gene comparing protein sequences throughout diverse phyla of metazoan species. None of the oncogenic missense mutations were found in germlines of any species of current genome and protein databases. Despite many tumors readily selecting these somatic mutations, the conclusion drawn from this study is that these variants are negatively rejected if encountered as a germline mutation. While cancer expansion ensues from dysregulated growth elicited by these mutations, this effect is likely detrimental to embryonic development and/or survival of multicellular organisms. Although all oncogenic mutations considered here are gain-of-function where five of the six increase activity of the encoded proteins, clonal advancement promotes tumor growth by these genomic changes without conferring selection advantages benefiting the organism or species.},
}
MeSH Terms:
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Animals
*Germ-Line Mutation/genetics
Humans
Neoplasms/genetics
Oncogenes/genetics
Mutation, Missense/genetics
Germ Cells/metabolism
RevDate: 2024-12-13
CmpDate: 2024-12-13
Ciliary length regulation by intraflagellar transport in zebrafish.
eLife, 13: pii:93168.
How cells regulate the size of their organelles remains a fundamental question in cell biology. Cilia, with their simple structure and surface localization, provide an ideal model for investigating organelle size control. However, most studies on cilia length regulation are primarily performed on several single-celled organisms. In contrast, the mechanism of length regulation in cilia across diverse cell types within multicellular organisms remains a mystery. Similar to humans, zebrafish contain diverse types of cilia with variable lengths. Taking advantage of the transparency of zebrafish embryos, we conducted a comprehensive investigation into intraflagellar transport (IFT), an essential process for ciliogenesis. By generating a transgenic line carrying Ift88-GFP transgene, we observed IFT in multiple types of cilia with varying lengths. Remarkably, cilia exhibited variable IFT speeds in different cell types, with longer cilia exhibiting faster IFT speeds. This increased IFT speed in longer cilia is likely not due to changes in common factors that regulate IFT, such as motor selection, BBSome proteins, or tubulin modification. Interestingly, longer cilia in the ear cristae tend to form larger IFT compared to shorter spinal cord cilia. Reducing the size of IFT particles by knocking down Ift88 slowed IFT speed and resulted in the formation of shorter cilia. Our study proposes an intriguing model of cilia length regulation via controlling IFT speed through the modulation of the size of the IFT complex. This discovery may provide further insights into our understanding of how organelle size is regulated in higher vertebrates.
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@article {pmid39671305,
year = {2024},
author = {Sun, Y and Chen, Z and Jin, M and Xie, H and Zhao, C},
title = {Ciliary length regulation by intraflagellar transport in zebrafish.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
doi = {10.7554/eLife.93168},
pmid = {39671305},
issn = {2050-084X},
support = {32125015//National Natural Science Foundation of China/ ; 31991194//National Natural Science Foundation of China/ ; 32100661//National Natural Science Foundation of China/ ; 2023M733344//China Postdoctoral Science Foundation/ ; },
mesh = {*Zebrafish/embryology ; Animals ; *Cilia/metabolism ; *Animals, Genetically Modified ; Biological Transport ; Zebrafish Proteins/metabolism/genetics ; Flagella/metabolism ; },
abstract = {How cells regulate the size of their organelles remains a fundamental question in cell biology. Cilia, with their simple structure and surface localization, provide an ideal model for investigating organelle size control. However, most studies on cilia length regulation are primarily performed on several single-celled organisms. In contrast, the mechanism of length regulation in cilia across diverse cell types within multicellular organisms remains a mystery. Similar to humans, zebrafish contain diverse types of cilia with variable lengths. Taking advantage of the transparency of zebrafish embryos, we conducted a comprehensive investigation into intraflagellar transport (IFT), an essential process for ciliogenesis. By generating a transgenic line carrying Ift88-GFP transgene, we observed IFT in multiple types of cilia with varying lengths. Remarkably, cilia exhibited variable IFT speeds in different cell types, with longer cilia exhibiting faster IFT speeds. This increased IFT speed in longer cilia is likely not due to changes in common factors that regulate IFT, such as motor selection, BBSome proteins, or tubulin modification. Interestingly, longer cilia in the ear cristae tend to form larger IFT compared to shorter spinal cord cilia. Reducing the size of IFT particles by knocking down Ift88 slowed IFT speed and resulted in the formation of shorter cilia. Our study proposes an intriguing model of cilia length regulation via controlling IFT speed through the modulation of the size of the IFT complex. This discovery may provide further insights into our understanding of how organelle size is regulated in higher vertebrates.},
}
MeSH Terms:
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*Zebrafish/embryology
Animals
*Cilia/metabolism
*Animals, Genetically Modified
Biological Transport
Zebrafish Proteins/metabolism/genetics
Flagella/metabolism
RevDate: 2024-12-09
Individuality Through Ecology: Rethinking the Evolution of Complex Life From an Externalist Perspective.
Ecology and evolution, 14(12):e70661 pii:ECE370661.
The evolution of complex life forms, exemplified by multicellular organisms, can be traced through a series of evolutionary transitions in individuality, beginning with the origin of life, followed by the emergence of the eukaryotic cell, and, among other transitions, culminating in the shift from unicellularity to multicellularity. Several attempts have been made to explain the origins of such transitions, many of which have been internalist (i.e., based largely on internal properties of ancestral entities). Here, we show how externalist perspectives can shed new light on questions pertaining to evolutionary transitions in individuality. We do this by presenting the ecological scaffolding framework in which properties of complex life forms arise from an external scaffold. Ultimately, we anticipate that progress will come from recognition of the importance of both the internalist and externalist modes of explanation. We illustrate this by considering an extension of the ecological scaffolding model in which cells modify the environment that later becomes the scaffold giving rise to multicellular individuality.
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@article {pmid39650545,
year = {2024},
author = {Bourrat, P and Takacs, P and Doulcier, G and Nitschke, MC and Black, AJ and Hammerschmidt, K and Rainey, PB},
title = {Individuality Through Ecology: Rethinking the Evolution of Complex Life From an Externalist Perspective.},
journal = {Ecology and evolution},
volume = {14},
number = {12},
pages = {e70661},
doi = {10.1002/ece3.70661},
pmid = {39650545},
issn = {2045-7758},
abstract = {The evolution of complex life forms, exemplified by multicellular organisms, can be traced through a series of evolutionary transitions in individuality, beginning with the origin of life, followed by the emergence of the eukaryotic cell, and, among other transitions, culminating in the shift from unicellularity to multicellularity. Several attempts have been made to explain the origins of such transitions, many of which have been internalist (i.e., based largely on internal properties of ancestral entities). Here, we show how externalist perspectives can shed new light on questions pertaining to evolutionary transitions in individuality. We do this by presenting the ecological scaffolding framework in which properties of complex life forms arise from an external scaffold. Ultimately, we anticipate that progress will come from recognition of the importance of both the internalist and externalist modes of explanation. We illustrate this by considering an extension of the ecological scaffolding model in which cells modify the environment that later becomes the scaffold giving rise to multicellular individuality.},
}
RevDate: 2024-12-06
Phylogenomics of neglected flagellated protists supports a revised eukaryotic tree of life.
Current biology : CB pii:S0960-9822(24)01502-1 [Epub ahead of print].
Eukaryotes evolved from prokaryotic predecessors in the early Proterozoic[1][,][2] and radiated from their already complex last common ancestor,[3] diversifying into several supergroups with unresolved deep evolutionary connections.[4] They evolved extremely diverse lifestyles, playing crucial roles in the carbon cycle.[5][,][6] Heterotrophic flagellates are arguably the most diverse eukaryotes[4][,][7][,][8][,][9] and often occupy basal positions in phylogenetic trees. However, many of them remain undersampled[4][,][10] and/or incertae sedis.[4][,][11][,][12][,][13][,][14][,][15][,][16][,][17][,][18] Progressive improvement of phylogenomic methods and a wider protist sampling have reshaped and consolidated major clades in the eukaryotic tree.[13][,][14][,][15][,][16][,][17][,][18][,][19] This is illustrated by the Opimoda,[14] one of the largest eukaryotic supergroups (Amoebozoa, Ancyromonadida, Apusomonadida, Breviatea, CRuMs [Collodictyon-Rigifila-Mantamonas], Malawimonadida, and Opisthokonta-including animals and fungi).[4][,][14][,][19][,][20][,][21][,][22] However, their deepest evolutionary relationships still remain uncertain. Here, we sequenced transcriptomes of poorly studied flagellates[23][,][24] (14 apusomonads,[25][,][26] 7 ancyromonads,[27] and 1 cultured Mediterranean strain of Meteora sporadica[17]) and conducted comprehensive phylogenomics analyses with an expanded taxon sampling of early-branching protists. Our findings support the monophyly of Opimoda, with CRuMs being sister to the Amorphea (amoebozoans, breviates, apusomonads, and opisthokonts) and ancyromonads and malawimonads forming a moderately supported clade. By mapping key complex phenotypic traits onto this phylogenetic framework, we infer an opimodan biflagellate ancestor with an excavate-like feeding groove, which ancyromonads subsequently lost. Although breviates and apusomonads retained the ancestral biflagellate state, some early-diverging Amorphea lost one or both flagella, facilitating the evolution of amoeboid morphologies, novel feeding modes, and palintomic cell division resulting in multinucleated cells. These innovations likely facilitated the subsequent evolution of fungal and metazoan multicellularity.
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@article {pmid39642877,
year = {2024},
author = {Torruella, G and Galindo, LJ and Moreira, D and López-García, P},
title = {Phylogenomics of neglected flagellated protists supports a revised eukaryotic tree of life.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2024.10.075},
pmid = {39642877},
issn = {1879-0445},
abstract = {Eukaryotes evolved from prokaryotic predecessors in the early Proterozoic[1][,][2] and radiated from their already complex last common ancestor,[3] diversifying into several supergroups with unresolved deep evolutionary connections.[4] They evolved extremely diverse lifestyles, playing crucial roles in the carbon cycle.[5][,][6] Heterotrophic flagellates are arguably the most diverse eukaryotes[4][,][7][,][8][,][9] and often occupy basal positions in phylogenetic trees. However, many of them remain undersampled[4][,][10] and/or incertae sedis.[4][,][11][,][12][,][13][,][14][,][15][,][16][,][17][,][18] Progressive improvement of phylogenomic methods and a wider protist sampling have reshaped and consolidated major clades in the eukaryotic tree.[13][,][14][,][15][,][16][,][17][,][18][,][19] This is illustrated by the Opimoda,[14] one of the largest eukaryotic supergroups (Amoebozoa, Ancyromonadida, Apusomonadida, Breviatea, CRuMs [Collodictyon-Rigifila-Mantamonas], Malawimonadida, and Opisthokonta-including animals and fungi).[4][,][14][,][19][,][20][,][21][,][22] However, their deepest evolutionary relationships still remain uncertain. Here, we sequenced transcriptomes of poorly studied flagellates[23][,][24] (14 apusomonads,[25][,][26] 7 ancyromonads,[27] and 1 cultured Mediterranean strain of Meteora sporadica[17]) and conducted comprehensive phylogenomics analyses with an expanded taxon sampling of early-branching protists. Our findings support the monophyly of Opimoda, with CRuMs being sister to the Amorphea (amoebozoans, breviates, apusomonads, and opisthokonts) and ancyromonads and malawimonads forming a moderately supported clade. By mapping key complex phenotypic traits onto this phylogenetic framework, we infer an opimodan biflagellate ancestor with an excavate-like feeding groove, which ancyromonads subsequently lost. Although breviates and apusomonads retained the ancestral biflagellate state, some early-diverging Amorphea lost one or both flagella, facilitating the evolution of amoeboid morphologies, novel feeding modes, and palintomic cell division resulting in multinucleated cells. These innovations likely facilitated the subsequent evolution of fungal and metazoan multicellularity.},
}
RevDate: 2024-12-04
CmpDate: 2024-12-04
Parrondo's paradox reveals counterintuitive wins in biology and decision making in society.
Physics of life reviews, 51:33-59.
Parrondo's paradox refers to the paradoxical phenomenon of combining two losing strategies in a certain manner to obtain a winning outcome. It has been applied to uncover unexpected outcomes across various disciplines, particularly at different spatiotemporal scales within ecosystems. In this article, we provide a comprehensive review of recent developments in Parrondo's paradox within the interdisciplinary realm of the physics of life, focusing on its significant applications across biology and the broader life sciences. Specifically, we examine its relevance from genetic pathways and phenotypic regulation, to intercellular interaction within multicellular organisms, and finally to the competition between populations and species in ecosystems. This phenomenon, spanning multiple biological domains and scales, enhances our understanding of the unified characteristics of life and reveals that adaptability in a drastically changing environment, rather than the inherent excellence of a trait, underpins survival in the process of evolution. We conclude by summarizing our findings and discussing future research directions that hold promise for advancing the field.
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@article {pmid39288541,
year = {2024},
author = {Wen, T and Cheong, KH},
title = {Parrondo's paradox reveals counterintuitive wins in biology and decision making in society.},
journal = {Physics of life reviews},
volume = {51},
number = {},
pages = {33-59},
doi = {10.1016/j.plrev.2024.08.002},
pmid = {39288541},
issn = {1873-1457},
mesh = {Humans ; Animals ; *Decision Making ; Biological Evolution ; Ecosystem ; Biology ; },
abstract = {Parrondo's paradox refers to the paradoxical phenomenon of combining two losing strategies in a certain manner to obtain a winning outcome. It has been applied to uncover unexpected outcomes across various disciplines, particularly at different spatiotemporal scales within ecosystems. In this article, we provide a comprehensive review of recent developments in Parrondo's paradox within the interdisciplinary realm of the physics of life, focusing on its significant applications across biology and the broader life sciences. Specifically, we examine its relevance from genetic pathways and phenotypic regulation, to intercellular interaction within multicellular organisms, and finally to the competition between populations and species in ecosystems. This phenomenon, spanning multiple biological domains and scales, enhances our understanding of the unified characteristics of life and reveals that adaptability in a drastically changing environment, rather than the inherent excellence of a trait, underpins survival in the process of evolution. We conclude by summarizing our findings and discussing future research directions that hold promise for advancing the field.},
}
MeSH Terms:
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Humans
Animals
*Decision Making
Biological Evolution
Ecosystem
Biology
RevDate: 2024-12-04
Functional expression and regulation of eukaryotic cytochrome P450 enzymes in surrogate microbial cell factories.
Engineering microbiology, 2(1):100011.
Cytochrome P450 (CYP) enzymes play crucial roles during the evolution and diversification of ancestral monocellular eukaryotes into multicellular eukaryotic organisms due to their essential functionalities including catalysis of housekeeping biochemical reactions, synthesis of diverse metabolites, detoxification of xenobiotics, and contribution to environmental adaptation. Eukaryotic CYPs with versatile functionalities are undeniably regarded as promising biocatalysts with great potential for biotechnological, pharmaceutical and chemical industry applications. Nevertheless, the modes of action and the challenges associated with these membrane-bound proteins have hampered the effective utilization of eukaryotic CYPs in a broader range. This review is focused on comprehensive and consolidated approaches to address the core challenges in heterologous expression of membrane-bound eukaryotic CYPs in different surrogate microbial cell factories, aiming to provide key insights for better studies and applications of diverse eukaryotic CYPs in the future. We also highlight the functional significance of the previously underrated cytochrome P450 reductases (CPRs) and provide a rational justification on the progression of CPR from auxiliary redox partner to function modulator in CYP catalysis.
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@article {pmid39628612,
year = {2022},
author = {Durairaj, P and Li, S},
title = {Functional expression and regulation of eukaryotic cytochrome P450 enzymes in surrogate microbial cell factories.},
journal = {Engineering microbiology},
volume = {2},
number = {1},
pages = {100011},
pmid = {39628612},
issn = {2667-3703},
abstract = {Cytochrome P450 (CYP) enzymes play crucial roles during the evolution and diversification of ancestral monocellular eukaryotes into multicellular eukaryotic organisms due to their essential functionalities including catalysis of housekeeping biochemical reactions, synthesis of diverse metabolites, detoxification of xenobiotics, and contribution to environmental adaptation. Eukaryotic CYPs with versatile functionalities are undeniably regarded as promising biocatalysts with great potential for biotechnological, pharmaceutical and chemical industry applications. Nevertheless, the modes of action and the challenges associated with these membrane-bound proteins have hampered the effective utilization of eukaryotic CYPs in a broader range. This review is focused on comprehensive and consolidated approaches to address the core challenges in heterologous expression of membrane-bound eukaryotic CYPs in different surrogate microbial cell factories, aiming to provide key insights for better studies and applications of diverse eukaryotic CYPs in the future. We also highlight the functional significance of the previously underrated cytochrome P450 reductases (CPRs) and provide a rational justification on the progression of CPR from auxiliary redox partner to function modulator in CYP catalysis.},
}
RevDate: 2024-12-01
CmpDate: 2024-12-01
Bridging the gap: Innovative human-based in vitro approaches for nanomaterials hazard assessment and their role in safe and sustainable by design, risk assessment, and life cycle assessment.
NanoImpact, 36:100533.
The application of nanomaterials in industry and consumer products is growing exponentially, which has pressed the development and use of predictive human in vitro models in pre-clinical analysis to closely extrapolate potential toxic effects in vivo. The conventional cytotoxicity investigation of nanomaterials using cell lines from cancer origin and culturing them two-dimensionally in a monolayer without mimicking the proper pathophysiological microenvironment may affect a precise prediction of in vitro effects at in vivo level. In recent years, complex in vitro models (also belonging to the new approach methodologies, NAMs) have been established in unicellular to multicellular cultures either by using cell lines, primary cells or induced pluripotent stem cells (iPSCs), and reconstituted into relevant biological dimensions mimicking in vivo conditions. These advanced in vitro models retain physiologically reliant exposure scenarios particularly appropriate for oral, dermal, respiratory, and intravenous administration of nanomaterials, which have the potential to improve the in vivo predictability and lead to reliable outcomes. In this perspective, we discuss recent developments and breakthroughs in using advanced human in vitro models for hazard assessment of nanomaterials. We identified fit-for-purpose requirements and remaining challenges for the successful implementation of in vitro data into nanomaterials Safe and Sustainable by Design (SSbD), Risk Assessment (RA), and Life Cycle Assessment (LCA). By addressing the gap between in vitro data generation and the utility of in vitro data for nanomaterial safety assessments, a prerequisite for SSbD approaches, we outlined potential key areas for future development.
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@article {pmid39454678,
year = {2024},
author = {Wu, J and Gupta, G and Buerki-Thurnherr, T and Nowack, B and Wick, P},
title = {Bridging the gap: Innovative human-based in vitro approaches for nanomaterials hazard assessment and their role in safe and sustainable by design, risk assessment, and life cycle assessment.},
journal = {NanoImpact},
volume = {36},
number = {},
pages = {100533},
doi = {10.1016/j.impact.2024.100533},
pmid = {39454678},
issn = {2452-0748},
mesh = {Humans ; *Nanostructures/toxicity/adverse effects ; Risk Assessment ; Toxicity Tests/methods ; },
abstract = {The application of nanomaterials in industry and consumer products is growing exponentially, which has pressed the development and use of predictive human in vitro models in pre-clinical analysis to closely extrapolate potential toxic effects in vivo. The conventional cytotoxicity investigation of nanomaterials using cell lines from cancer origin and culturing them two-dimensionally in a monolayer without mimicking the proper pathophysiological microenvironment may affect a precise prediction of in vitro effects at in vivo level. In recent years, complex in vitro models (also belonging to the new approach methodologies, NAMs) have been established in unicellular to multicellular cultures either by using cell lines, primary cells or induced pluripotent stem cells (iPSCs), and reconstituted into relevant biological dimensions mimicking in vivo conditions. These advanced in vitro models retain physiologically reliant exposure scenarios particularly appropriate for oral, dermal, respiratory, and intravenous administration of nanomaterials, which have the potential to improve the in vivo predictability and lead to reliable outcomes. In this perspective, we discuss recent developments and breakthroughs in using advanced human in vitro models for hazard assessment of nanomaterials. We identified fit-for-purpose requirements and remaining challenges for the successful implementation of in vitro data into nanomaterials Safe and Sustainable by Design (SSbD), Risk Assessment (RA), and Life Cycle Assessment (LCA). By addressing the gap between in vitro data generation and the utility of in vitro data for nanomaterial safety assessments, a prerequisite for SSbD approaches, we outlined potential key areas for future development.},
}
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Humans
*Nanostructures/toxicity/adverse effects
Risk Assessment
Toxicity Tests/methods
RevDate: 2024-12-01
CmpDate: 2024-12-01
Brain and cognition: The need for a broader biological perspective to overcome old biases.
Neuroscience and biobehavioral reviews, 167:105928.
Even with accumulating knowledge, no consensus regarding the understanding of intelligence or cognition exists, and the universal brain bases for these functions remain unclear. Traditionally, our understanding of cognition is based on self-evident principles that appear indisputable when looking only at our species; however, this can distance us from understanding its essence (anthropocentrism, corticocentrism, intellectocentrism, neurocentrism, and idea of orthogenesis of brain evolution). Herein, we use several examples from biology to demonstrate the usefulness of comparative ways of thinking in relativizing these biases. We discuss the relationship between the number of neurons and cognition and draw attention to the highly developed cognitive performance of animals with small brains, to some "tricks" of evolution, to how animals cope with small hardware, to some animals with high-quality brains with an alternative architecture to vertebrates, and to surprising basal cognitive skills in aneural, unicellular organisms. Cognition can be supplemented by the idea of a multicellular organism as a continuum, with many levels of cognitive function, including the possible basal learning in single cells.
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@article {pmid39427812,
year = {2024},
author = {Dvořáček, J and Kodrík, D},
title = {Brain and cognition: The need for a broader biological perspective to overcome old biases.},
journal = {Neuroscience and biobehavioral reviews},
volume = {167},
number = {},
pages = {105928},
doi = {10.1016/j.neubiorev.2024.105928},
pmid = {39427812},
issn = {1873-7528},
mesh = {*Cognition/physiology ; *Brain/physiology ; Animals ; Humans ; *Biological Evolution ; Neurons/physiology ; Intelligence/physiology ; },
abstract = {Even with accumulating knowledge, no consensus regarding the understanding of intelligence or cognition exists, and the universal brain bases for these functions remain unclear. Traditionally, our understanding of cognition is based on self-evident principles that appear indisputable when looking only at our species; however, this can distance us from understanding its essence (anthropocentrism, corticocentrism, intellectocentrism, neurocentrism, and idea of orthogenesis of brain evolution). Herein, we use several examples from biology to demonstrate the usefulness of comparative ways of thinking in relativizing these biases. We discuss the relationship between the number of neurons and cognition and draw attention to the highly developed cognitive performance of animals with small brains, to some "tricks" of evolution, to how animals cope with small hardware, to some animals with high-quality brains with an alternative architecture to vertebrates, and to surprising basal cognitive skills in aneural, unicellular organisms. Cognition can be supplemented by the idea of a multicellular organism as a continuum, with many levels of cognitive function, including the possible basal learning in single cells.},
}
MeSH Terms:
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*Cognition/physiology
*Brain/physiology
Animals
Humans
*Biological Evolution
Neurons/physiology
Intelligence/physiology
RevDate: 2024-11-29
CmpDate: 2024-11-30
Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.
Molecular cancer, 23(1):267.
Cell death is a fundamental part of life for metazoans. To maintain the balance between cell proliferation and metabolism of human bodies, a certain number of cells need to be removed regularly. Hence, the mechanisms of cell death have been preserved during the evolution of multicellular organisms. Tumorigenesis is closely related with exceptional inhibition of cell death. Mutations or defects in cell death-related genes block the elimination of abnormal cells and enhance the resistance of malignant cells to chemotherapy. Therefore, the investigation of cell death mechanisms enables the development of drugs that directly induce tumor cell death. In the guidelines updated by the Cell Death Nomenclature Committee (NCCD) in 2018, cell death was classified into 12 types according to morphological, biochemical and functional classification, including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, PARP-1 parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence and mitotic catastrophe. The mechanistic relationships between epigenetic controls and cell death in cancer progression were previously unclear. In this review, we will summarize the mechanisms of cell death pathways and corresponding epigenetic regulations. Also, we will explore the extensive interactions between these pathways and discuss the mechanisms of cell death in epigenetics which bring benefits to tumor therapy.
Additional Links: PMID-39614268
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@article {pmid39614268,
year = {2024},
author = {He, R and Liu, Y and Fu, W and He, X and Liu, S and Xiao, D and Tao, Y},
title = {Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.},
journal = {Molecular cancer},
volume = {23},
number = {1},
pages = {267},
pmid = {39614268},
issn = {1476-4598},
mesh = {Humans ; *Neoplasms/genetics/pathology/metabolism ; *Epigenesis, Genetic ; Animals ; *Disease Progression ; *Regulated Cell Death/genetics ; Gene Expression Regulation, Neoplastic ; Signal Transduction ; },
abstract = {Cell death is a fundamental part of life for metazoans. To maintain the balance between cell proliferation and metabolism of human bodies, a certain number of cells need to be removed regularly. Hence, the mechanisms of cell death have been preserved during the evolution of multicellular organisms. Tumorigenesis is closely related with exceptional inhibition of cell death. Mutations or defects in cell death-related genes block the elimination of abnormal cells and enhance the resistance of malignant cells to chemotherapy. Therefore, the investigation of cell death mechanisms enables the development of drugs that directly induce tumor cell death. In the guidelines updated by the Cell Death Nomenclature Committee (NCCD) in 2018, cell death was classified into 12 types according to morphological, biochemical and functional classification, including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, PARP-1 parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence and mitotic catastrophe. The mechanistic relationships between epigenetic controls and cell death in cancer progression were previously unclear. In this review, we will summarize the mechanisms of cell death pathways and corresponding epigenetic regulations. Also, we will explore the extensive interactions between these pathways and discuss the mechanisms of cell death in epigenetics which bring benefits to tumor therapy.},
}
MeSH Terms:
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Humans
*Neoplasms/genetics/pathology/metabolism
*Epigenesis, Genetic
Animals
*Disease Progression
*Regulated Cell Death/genetics
Gene Expression Regulation, Neoplastic
Signal Transduction
RevDate: 2024-11-28
CmpDate: 2024-11-28
Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems.
Cell, 187(24):6943-6965.e39.
Brown seaweeds are keystone species of coastal ecosystems, often forming extensive underwater forests, and are under considerable threat from climate change. In this study, analysis of multiple genomes has provided insights across the entire evolutionary history of this lineage, from initial emergence, through later diversification of the brown algal orders, down to microevolutionary events at the genus level. Emergence of the brown algal lineage was associated with a marked gain of new orthologous gene families, enhanced protein domain rearrangement, increased horizontal gene transfer events, and the acquisition of novel signaling molecules and key metabolic pathways, the latter notably related to biosynthesis of the alginate-based extracellular matrix, and halogen and phlorotannin biosynthesis. We show that brown algal genome diversification is tightly linked to phenotypic divergence, including changes in life cycle strategy and zoid flagellar structure. The study also showed that integration of large viral genomes has had a significant impact on brown algal genome content throughout the emergence of the lineage.
Additional Links: PMID-39571576
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@article {pmid39571576,
year = {2024},
author = {Denoeud, F and Godfroy, O and Cruaud, C and Heesch, S and Nehr, Z and Tadrent, N and Couloux, A and Brillet-Guéguen, L and Delage, L and Mckeown, D and Motomura, T and Sussfeld, D and Fan, X and Mazéas, L and Terrapon, N and Barrera-Redondo, J and Petroll, R and Reynes, L and Choi, SW and Jo, J and Uthanumallian, K and Bogaert, K and Duc, C and Ratchinski, P and Lipinska, A and Noel, B and Murphy, EA and Lohr, M and Khatei, A and Hamon-Giraud, P and Vieira, C and Avia, K and Akerfors, SS and Akita, S and Badis, Y and Barbeyron, T and Belcour, A and Berrabah, W and Blanquart, S and Bouguerba-Collin, A and Bringloe, T and Cattolico, RA and Cormier, A and Cruz de Carvalho, H and Dallet, R and De Clerck, O and Debit, A and Denis, E and Destombe, C and Dinatale, E and Dittami, S and Drula, E and Faugeron, S and Got, J and Graf, L and Groisillier, A and Guillemin, ML and Harms, L and Hatchett, WJ and Henrissat, B and Hoarau, G and Jollivet, C and Jueterbock, A and Kayal, E and Knoll, AH and Kogame, K and Le Bars, A and Leblanc, C and Le Gall, L and Ley, R and Liu, X and LoDuca, ST and Lopez, PJ and Lopez, P and Manirakiza, E and Massau, K and Mauger, S and Mest, L and Michel, G and Monteiro, C and Nagasato, C and Nègre, D and Pelletier, E and Phillips, N and Potin, P and Rensing, SA and Rousselot, E and Rousvoal, S and Schroeder, D and Scornet, D and Siegel, A and Tirichine, L and Tonon, T and Valentin, K and Verbruggen, H and Weinberger, F and Wheeler, G and Kawai, H and Peters, AF and Yoon, HS and Hervé, C and Ye, N and Bapteste, E and Valero, M and Markov, GV and Corre, E and Coelho, SM and Wincker, P and Aury, JM and Cock, JM},
title = {Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems.},
journal = {Cell},
volume = {187},
number = {24},
pages = {6943-6965.e39},
doi = {10.1016/j.cell.2024.10.049},
pmid = {39571576},
issn = {1097-4172},
mesh = {*Phaeophyceae/genetics ; *Ecosystem ; *Phylogeny ; *Genomics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genome/genetics ; },
abstract = {Brown seaweeds are keystone species of coastal ecosystems, often forming extensive underwater forests, and are under considerable threat from climate change. In this study, analysis of multiple genomes has provided insights across the entire evolutionary history of this lineage, from initial emergence, through later diversification of the brown algal orders, down to microevolutionary events at the genus level. Emergence of the brown algal lineage was associated with a marked gain of new orthologous gene families, enhanced protein domain rearrangement, increased horizontal gene transfer events, and the acquisition of novel signaling molecules and key metabolic pathways, the latter notably related to biosynthesis of the alginate-based extracellular matrix, and halogen and phlorotannin biosynthesis. We show that brown algal genome diversification is tightly linked to phenotypic divergence, including changes in life cycle strategy and zoid flagellar structure. The study also showed that integration of large viral genomes has had a significant impact on brown algal genome content throughout the emergence of the lineage.},
}
MeSH Terms:
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hide MeSH Terms
*Phaeophyceae/genetics
*Ecosystem
*Phylogeny
*Genomics
*Evolution, Molecular
Gene Transfer, Horizontal
Genome/genetics
RevDate: 2024-11-28
Multiple mechanisms for licensing human replication origins.
Nature [Epub ahead of print].
Loading of replicative helicases is obligatory for the assembly of DNA replication machineries. The eukaryotic MCM2-7 replicative helicase motor is deposited onto DNA by the origin recognition complex (ORC) and co-loader proteins as a head-to-head double hexamer to license replication origins. Although extensively studied in budding yeast[1-4], the mechanisms of origin licensing in multicellular eukaryotes remain poorly defined. Here we use biochemical reconstitution and electron microscopy to reconstruct the human MCM loading pathway. We find that unlike in yeast, the ORC6 subunit of the ORC is not essential for-but enhances-human MCM loading. Electron microscopy analyses identify several intermediates en route to MCM double hexamer formation in the presence and absence of ORC6, including a DNA-loaded, closed-ring MCM single hexamer intermediate that can mature into a head-to-head double hexamer through multiple mechanisms. ORC6 and ORC3 facilitate the recruitment of the ORC to the dimerization interface of the first hexamer into MCM-ORC (MO) complexes that are distinct from the yeast MO complex[5,6] and may orient the ORC for second MCM hexamer loading. Additionally, MCM double hexamer formation can proceed through dimerization of independently loaded MCM single hexamers, promoted by a propensity of human MCM2-7 hexamers to self-dimerize. This flexibility in human MCM loading may provide resilience against cellular replication stress, and the reconstitution system will enable studies addressing outstanding questions regarding DNA replication initiation and replication-coupled events in the future.
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@article {pmid39604729,
year = {2024},
author = {Yang, R and Hunker, O and Wise, M and Bleichert, F},
title = {Multiple mechanisms for licensing human replication origins.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {39604729},
issn = {1476-4687},
abstract = {Loading of replicative helicases is obligatory for the assembly of DNA replication machineries. The eukaryotic MCM2-7 replicative helicase motor is deposited onto DNA by the origin recognition complex (ORC) and co-loader proteins as a head-to-head double hexamer to license replication origins. Although extensively studied in budding yeast[1-4], the mechanisms of origin licensing in multicellular eukaryotes remain poorly defined. Here we use biochemical reconstitution and electron microscopy to reconstruct the human MCM loading pathway. We find that unlike in yeast, the ORC6 subunit of the ORC is not essential for-but enhances-human MCM loading. Electron microscopy analyses identify several intermediates en route to MCM double hexamer formation in the presence and absence of ORC6, including a DNA-loaded, closed-ring MCM single hexamer intermediate that can mature into a head-to-head double hexamer through multiple mechanisms. ORC6 and ORC3 facilitate the recruitment of the ORC to the dimerization interface of the first hexamer into MCM-ORC (MO) complexes that are distinct from the yeast MO complex[5,6] and may orient the ORC for second MCM hexamer loading. Additionally, MCM double hexamer formation can proceed through dimerization of independently loaded MCM single hexamers, promoted by a propensity of human MCM2-7 hexamers to self-dimerize. This flexibility in human MCM loading may provide resilience against cellular replication stress, and the reconstitution system will enable studies addressing outstanding questions regarding DNA replication initiation and replication-coupled events in the future.},
}
RevDate: 2024-11-28
CmpDate: 2024-11-28
Structural Diversity and Distribution of Nuclear Matrix Constituent Protein Class Nuclear Lamina Proteins in Streptophytic Algae.
Genome biology and evolution, 16(11):.
Nuclear matrix constituent proteins in plants function like animal lamins, providing the structural foundation of the nuclear lamina and regulating nuclear organization and morphology. Although they are well characterized in angiosperms, the presence and structure of nuclear matrix constituent proteins in more distantly related species, such as streptophytic algae, are relatively unknown. The rapid evolution of nuclear matrix constituent proteins throughout the plant lineage has caused a divergence in protein sequence that makes similarity-based searches less effective. Structural features are more likely to be conserved compared to primary amino acid sequence; therefore, we developed a filtration protocol to search for diverged nuclear matrix constituent proteins based on four physical characteristics: intrinsically disordered content, isoelectric point, number of amino acids, and the presence of a central coiled-coil domain. By setting parameters to recognize the properties of bona fide nuclear matrix constituent protein proteins in angiosperms, we filtered eight complete proteomes from streptophytic algae species and identified strong nuclear matrix constituent protein candidates in six taxa in the Classes Zygnematophyceae, Charophyceae, and Klebsormidiophyceae. Through analysis of these proteins, we observed structural variance in domain size between nuclear matrix constituent proteins in algae and land plants, as well as a single block of amino acid conservation. Our analysis indicates that nuclear matrix constituent proteins are absent in the Mesostigmatophyceae. The presence versus absence of nuclear matrix constituent protein proteins does not correlate with the distribution of different forms of mitosis (e.g. closed/semi-closed/open) but does correspond to the transition from unicellularity to multicellularity in the streptophytic algae, suggesting that a nuclear matrix constituent protein-based nucleoskeleton plays important roles in supporting cell-to-cell interactions.
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@article {pmid39539009,
year = {2024},
author = {Kosztyo, BS and Richards, EJ},
title = {Structural Diversity and Distribution of Nuclear Matrix Constituent Protein Class Nuclear Lamina Proteins in Streptophytic Algae.},
journal = {Genome biology and evolution},
volume = {16},
number = {11},
pages = {},
doi = {10.1093/gbe/evae244},
pmid = {39539009},
issn = {1759-6653},
support = {URoL-2022048//National Science Foundation/ ; },
mesh = {*Streptophyta/metabolism/genetics ; Plant Proteins/genetics/metabolism/chemistry ; Nuclear Lamina/metabolism ; Nuclear Matrix/metabolism ; Algal Proteins/metabolism/chemistry/genetics ; Phylogeny ; Nuclear Proteins/metabolism/genetics/chemistry ; Amino Acid Sequence ; Evolution, Molecular ; Proteome ; },
abstract = {Nuclear matrix constituent proteins in plants function like animal lamins, providing the structural foundation of the nuclear lamina and regulating nuclear organization and morphology. Although they are well characterized in angiosperms, the presence and structure of nuclear matrix constituent proteins in more distantly related species, such as streptophytic algae, are relatively unknown. The rapid evolution of nuclear matrix constituent proteins throughout the plant lineage has caused a divergence in protein sequence that makes similarity-based searches less effective. Structural features are more likely to be conserved compared to primary amino acid sequence; therefore, we developed a filtration protocol to search for diverged nuclear matrix constituent proteins based on four physical characteristics: intrinsically disordered content, isoelectric point, number of amino acids, and the presence of a central coiled-coil domain. By setting parameters to recognize the properties of bona fide nuclear matrix constituent protein proteins in angiosperms, we filtered eight complete proteomes from streptophytic algae species and identified strong nuclear matrix constituent protein candidates in six taxa in the Classes Zygnematophyceae, Charophyceae, and Klebsormidiophyceae. Through analysis of these proteins, we observed structural variance in domain size between nuclear matrix constituent proteins in algae and land plants, as well as a single block of amino acid conservation. Our analysis indicates that nuclear matrix constituent proteins are absent in the Mesostigmatophyceae. The presence versus absence of nuclear matrix constituent protein proteins does not correlate with the distribution of different forms of mitosis (e.g. closed/semi-closed/open) but does correspond to the transition from unicellularity to multicellularity in the streptophytic algae, suggesting that a nuclear matrix constituent protein-based nucleoskeleton plays important roles in supporting cell-to-cell interactions.},
}
MeSH Terms:
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*Streptophyta/metabolism/genetics
Plant Proteins/genetics/metabolism/chemistry
Nuclear Lamina/metabolism
Nuclear Matrix/metabolism
Algal Proteins/metabolism/chemistry/genetics
Phylogeny
Nuclear Proteins/metabolism/genetics/chemistry
Amino Acid Sequence
Evolution, Molecular
Proteome
RevDate: 2024-11-27
CmpDate: 2024-11-27
The Evolution of Complex Multicellularity in Land Plants.
Genes, 15(11): pii:genes15111472.
The evolution of complex multicellularity in land plants represents a pivotal event in the history of life on Earth, characterized by significant increases in biological complexity. This transition, classified as a Major Evolutionary Transition (MET), is best understood through the framework of Evolutionary Transitions in Individuality (ETIs), which focuses on formerly independent entities forming higher-level units that lose their reproductive autonomy. While much of the ETI literature has concentrated on the early stages of multicellularity, such as the formation and maintenance stages, this paper seeks to address the less explored transformation stage. To do so, we apply an approach that we call Transitions in Structural Complexity (TSCs), which focuses on the emergence of new units of organization via the three key evolutionary processes of modularization, subfunctionalization, and integration to the evolution of land plants. To lay the groundwork, we first explore the relationships between sex, individuality, and units of selection to highlight a sexual life cycle-based perspective on ETIs by examining the early stages of the transition to multicellularity (formation) in the sexual life cycle of the unicellular common ancestor of land plants, emphasizing the differences between the transition to multicellularity in eumetazoans and land plants. We then directly apply the TSC approach in this group, identifying key evolutionary events such as the distinct evolutionary innovations like shoot, root, vascular systems, and specialized reproductive structures, arguing that bringing these under the broader rubric of TSCs affords a degree of explanatory unification. By examining these evolutionary processes, this paper provides a new perspective on the evolution of multicellularity in land plants, highlighting both parallels and distinctions with the animal kingdom.
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@article {pmid39596672,
year = {2024},
author = {Madhani, H and Nejad Kourki, A},
title = {The Evolution of Complex Multicellularity in Land Plants.},
journal = {Genes},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/genes15111472},
pmid = {39596672},
issn = {2073-4425},
mesh = {*Embryophyta/genetics/growth & development ; *Biological Evolution ; },
abstract = {The evolution of complex multicellularity in land plants represents a pivotal event in the history of life on Earth, characterized by significant increases in biological complexity. This transition, classified as a Major Evolutionary Transition (MET), is best understood through the framework of Evolutionary Transitions in Individuality (ETIs), which focuses on formerly independent entities forming higher-level units that lose their reproductive autonomy. While much of the ETI literature has concentrated on the early stages of multicellularity, such as the formation and maintenance stages, this paper seeks to address the less explored transformation stage. To do so, we apply an approach that we call Transitions in Structural Complexity (TSCs), which focuses on the emergence of new units of organization via the three key evolutionary processes of modularization, subfunctionalization, and integration to the evolution of land plants. To lay the groundwork, we first explore the relationships between sex, individuality, and units of selection to highlight a sexual life cycle-based perspective on ETIs by examining the early stages of the transition to multicellularity (formation) in the sexual life cycle of the unicellular common ancestor of land plants, emphasizing the differences between the transition to multicellularity in eumetazoans and land plants. We then directly apply the TSC approach in this group, identifying key evolutionary events such as the distinct evolutionary innovations like shoot, root, vascular systems, and specialized reproductive structures, arguing that bringing these under the broader rubric of TSCs affords a degree of explanatory unification. By examining these evolutionary processes, this paper provides a new perspective on the evolution of multicellularity in land plants, highlighting both parallels and distinctions with the animal kingdom.},
}
MeSH Terms:
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*Embryophyta/genetics/growth & development
*Biological Evolution
RevDate: 2024-11-27
CmpDate: 2024-11-27
An Orthologics Study of the Notch Signaling Pathway.
Genes, 15(11): pii:genes15111452.
The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane-embedded ligands, instructs a Receiver cell, bearing membrane-embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach, providing a comprehensive basis for the study. Using BLAST searches, orthologs were identified for all the 49 components of the Notch signaling pathway. The historical time course of integration of these proteins, as the animals evolved, was elucidated. Insofar as cell-to-cell communication is of relevance only in multicellular animals, it is not surprising that the Notch system became functional only with the evolutionary appearance of Metazoa, the first multicellular animals. Porifera contributed a quarter of the Notch pathway proteins, the Cnidaria brought the total to one-half, but the system reached completion only when humans appeared. A literature search elucidated the roles of the Notch system's components in modern descendants of the ortholog-contributing ancestors. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans, was identified as a possible pre-Metazoan ancestor of all three of the Notch pathway proteins, DLL, JAG, and NOTCH. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in ancestral unicellular organisms.
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@article {pmid39596652,
year = {2024},
author = {Stein, WD},
title = {An Orthologics Study of the Notch Signaling Pathway.},
journal = {Genes},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/genes15111452},
pmid = {39596652},
issn = {2073-4425},
mesh = {*Signal Transduction ; *Receptors, Notch/metabolism/genetics ; Animals ; Humans ; Evolution, Molecular ; Membrane Proteins/genetics/metabolism ; Phylogeny ; },
abstract = {The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane-embedded ligands, instructs a Receiver cell, bearing membrane-embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach, providing a comprehensive basis for the study. Using BLAST searches, orthologs were identified for all the 49 components of the Notch signaling pathway. The historical time course of integration of these proteins, as the animals evolved, was elucidated. Insofar as cell-to-cell communication is of relevance only in multicellular animals, it is not surprising that the Notch system became functional only with the evolutionary appearance of Metazoa, the first multicellular animals. Porifera contributed a quarter of the Notch pathway proteins, the Cnidaria brought the total to one-half, but the system reached completion only when humans appeared. A literature search elucidated the roles of the Notch system's components in modern descendants of the ortholog-contributing ancestors. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans, was identified as a possible pre-Metazoan ancestor of all three of the Notch pathway proteins, DLL, JAG, and NOTCH. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in ancestral unicellular organisms.},
}
MeSH Terms:
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*Signal Transduction
*Receptors, Notch/metabolism/genetics
Animals
Humans
Evolution, Molecular
Membrane Proteins/genetics/metabolism
Phylogeny
RevDate: 2024-11-27
CmpDate: 2024-11-27
Loss of Sterol Biosynthesis in Economically Important Plant Pests and Pathogens: A Review of a Potential Target for Pest Control.
Biomolecules, 14(11): pii:biom14111435.
Sterol biosynthesis is a crucial metabolic pathway in plants and various plant pathogens. Their vital physiological role in multicellular organisms and their effects on growth and reproduction underline their importance as membrane compounds, hormone precursors, and signaling molecules. Insects, nematodes, and oomycetes of the Peronosporales group, which harbor important agricultural pests and pathogens, have lost the ability to synthesize their own sterols. These organisms rely on the acquisition of sterols from their host and are dependent on the sterol composition of the host. It is thought that sterol-synthesizing enzymes were lost during co-evolution with the hosts, which provided the organisms with sufficient amounts of the required sterols. To meet the essential requirements of these organisms, some sterol auxotrophs retained a few remaining sterol-modifying enzymes. Several molecular and biochemical investigations have suggested promising avenues for pest and pathogen control by targeting host sterol composition, sterol uptake, or sterol modification in organisms that have lost the ability to biosynthesize sterol de novo. This review examines the loss of sterol biosynthesis de novo in insects, nematodes, and oomycetes with the aim of investigating the sterol metabolic constraints and sterol acquisition of these organisms. This will shed light on its potential as a control target for the management of sterol-dependent organisms in a comprehensive agronomic approach.
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@article {pmid39595611,
year = {2024},
author = {Dahlin, P and Ruthes, AC},
title = {Loss of Sterol Biosynthesis in Economically Important Plant Pests and Pathogens: A Review of a Potential Target for Pest Control.},
journal = {Biomolecules},
volume = {14},
number = {11},
pages = {},
doi = {10.3390/biom14111435},
pmid = {39595611},
issn = {2218-273X},
mesh = {*Sterols/metabolism/biosynthesis ; Animals ; *Plants/metabolism/parasitology ; *Nematoda/metabolism ; *Insecta/metabolism ; Pest Control ; Oomycetes/metabolism ; Plant Diseases/parasitology/microbiology ; },
abstract = {Sterol biosynthesis is a crucial metabolic pathway in plants and various plant pathogens. Their vital physiological role in multicellular organisms and their effects on growth and reproduction underline their importance as membrane compounds, hormone precursors, and signaling molecules. Insects, nematodes, and oomycetes of the Peronosporales group, which harbor important agricultural pests and pathogens, have lost the ability to synthesize their own sterols. These organisms rely on the acquisition of sterols from their host and are dependent on the sterol composition of the host. It is thought that sterol-synthesizing enzymes were lost during co-evolution with the hosts, which provided the organisms with sufficient amounts of the required sterols. To meet the essential requirements of these organisms, some sterol auxotrophs retained a few remaining sterol-modifying enzymes. Several molecular and biochemical investigations have suggested promising avenues for pest and pathogen control by targeting host sterol composition, sterol uptake, or sterol modification in organisms that have lost the ability to biosynthesize sterol de novo. This review examines the loss of sterol biosynthesis de novo in insects, nematodes, and oomycetes with the aim of investigating the sterol metabolic constraints and sterol acquisition of these organisms. This will shed light on its potential as a control target for the management of sterol-dependent organisms in a comprehensive agronomic approach.},
}
MeSH Terms:
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*Sterols/metabolism/biosynthesis
Animals
*Plants/metabolism/parasitology
*Nematoda/metabolism
*Insecta/metabolism
Pest Control
Oomycetes/metabolism
Plant Diseases/parasitology/microbiology
RevDate: 2024-11-25
CmpDate: 2024-11-25
The Acrasis kona genome and developmental transcriptomes reveal deep origins of eukaryotic multicellular pathways.
Nature communications, 15(1):10197.
Acrasids are amoebae with the capacity to form multicellular fruiting bodies in a process known as aggregative multicellularity (AGM). This makes acrasids the only known example of multicellularity among the earliest branches of eukaryotes (the former Excavata). Here, we report the Acrasis kona genome sequence plus transcriptomes from pre-, mid- and post-developmental stages. The genome is rich in novelty and genes with strong signatures of horizontal transfer, and multigene families encode nearly half of the amoeba's predicted proteome. Development in A. kona appears molecularly simple relative to the AGM model, Dictyostelium discoideum. However, the acrasid also differs from the dictyostelid in that it does not appear to be starving during development. Instead, developing A. kona appears to be very metabolically active, does not induce autophagy and does not up-regulate its proteasomal genes. Together, these observations strongly suggest that starvation is not essential for AGM development. Nonetheless, development in the two amoebae appears to employ remarkably similar pathways for signaling, motility and, potentially, construction of an extracellular matrix surrounding the developing cell mass. Much of this similarity is also shared with animal development, suggesting that much of the basic tool kit for multicellular development arose early in eukaryote evolution.
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@article {pmid39587099,
year = {2024},
author = {Sheikh, S and Fu, CJ and Brown, MW and Baldauf, SL},
title = {The Acrasis kona genome and developmental transcriptomes reveal deep origins of eukaryotic multicellular pathways.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {10197},
pmid = {39587099},
issn = {2041-1723},
support = {VR 2017-04351//Vetenskapsrådet (Swedish Research Council)/ ; 2100888//National Science Foundation (NSF)/ ; },
mesh = {*Transcriptome ; *Dictyostelium/genetics/growth & development ; Genome, Protozoan ; Amoeba/genetics ; Phylogeny ; Gene Transfer, Horizontal ; Protozoan Proteins/genetics/metabolism ; Proteome/metabolism/genetics ; Genome ; },
abstract = {Acrasids are amoebae with the capacity to form multicellular fruiting bodies in a process known as aggregative multicellularity (AGM). This makes acrasids the only known example of multicellularity among the earliest branches of eukaryotes (the former Excavata). Here, we report the Acrasis kona genome sequence plus transcriptomes from pre-, mid- and post-developmental stages. The genome is rich in novelty and genes with strong signatures of horizontal transfer, and multigene families encode nearly half of the amoeba's predicted proteome. Development in A. kona appears molecularly simple relative to the AGM model, Dictyostelium discoideum. However, the acrasid also differs from the dictyostelid in that it does not appear to be starving during development. Instead, developing A. kona appears to be very metabolically active, does not induce autophagy and does not up-regulate its proteasomal genes. Together, these observations strongly suggest that starvation is not essential for AGM development. Nonetheless, development in the two amoebae appears to employ remarkably similar pathways for signaling, motility and, potentially, construction of an extracellular matrix surrounding the developing cell mass. Much of this similarity is also shared with animal development, suggesting that much of the basic tool kit for multicellular development arose early in eukaryote evolution.},
}
MeSH Terms:
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*Transcriptome
*Dictyostelium/genetics/growth & development
Genome, Protozoan
Amoeba/genetics
Phylogeny
Gene Transfer, Horizontal
Protozoan Proteins/genetics/metabolism
Proteome/metabolism/genetics
Genome
RevDate: 2024-11-25
CmpDate: 2024-11-25
The Prokaryotic Roots of Eukaryotic Immune Systems.
Annual review of genetics, 58(1):365-389.
Over the past two decades, studies have revealed profound evolutionary connections between prokaryotic and eukaryotic immune systems, challenging the notion of their unrelatedness. Immune systems across the tree of life share an operational framework, shaping their biochemical logic and evolutionary trajectories. The diversification of immune genes in the prokaryotic superkingdoms, followed by lateral transfer to eukaryotes, was central to the emergence of innate immunity in the latter. These include protein domains related to nucleotide second messenger-dependent systems, NAD+/nucleotide degradation, and P-loop NTPase domains of the STAND and GTPase clades playing pivotal roles in eukaryotic immunity and inflammation. Moreover, several domains orchestrating programmed cell death, ultimately of prokaryotic provenance, suggest an intimate link between immunity and the emergence of multicellularity in eukaryotes such as animals. While eukaryotes directly adopted some proteins from bacterial immune systems, they repurposed others for new immune functions from bacterial interorganismal conflict systems. These emerging immune components hold substantial biotechnological potential.
Additional Links: PMID-39265037
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@article {pmid39265037,
year = {2024},
author = {Aravind, L and Nicastro, GG and Iyer, LM and Burroughs, AM},
title = {The Prokaryotic Roots of Eukaryotic Immune Systems.},
journal = {Annual review of genetics},
volume = {58},
number = {1},
pages = {365-389},
doi = {10.1146/annurev-genet-111523-102448},
pmid = {39265037},
issn = {1545-2948},
mesh = {Animals ; *Prokaryotic Cells/immunology/metabolism ; *Eukaryota/genetics/immunology ; Humans ; *Immunity, Innate/genetics ; Immune System/immunology/metabolism ; Bacteria/genetics/immunology/metabolism ; Evolution, Molecular ; Phylogeny ; Biological Evolution ; },
abstract = {Over the past two decades, studies have revealed profound evolutionary connections between prokaryotic and eukaryotic immune systems, challenging the notion of their unrelatedness. Immune systems across the tree of life share an operational framework, shaping their biochemical logic and evolutionary trajectories. The diversification of immune genes in the prokaryotic superkingdoms, followed by lateral transfer to eukaryotes, was central to the emergence of innate immunity in the latter. These include protein domains related to nucleotide second messenger-dependent systems, NAD+/nucleotide degradation, and P-loop NTPase domains of the STAND and GTPase clades playing pivotal roles in eukaryotic immunity and inflammation. Moreover, several domains orchestrating programmed cell death, ultimately of prokaryotic provenance, suggest an intimate link between immunity and the emergence of multicellularity in eukaryotes such as animals. While eukaryotes directly adopted some proteins from bacterial immune systems, they repurposed others for new immune functions from bacterial interorganismal conflict systems. These emerging immune components hold substantial biotechnological potential.},
}
MeSH Terms:
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Animals
*Prokaryotic Cells/immunology/metabolism
*Eukaryota/genetics/immunology
Humans
*Immunity, Innate/genetics
Immune System/immunology/metabolism
Bacteria/genetics/immunology/metabolism
Evolution, Molecular
Phylogeny
Biological Evolution
RevDate: 2024-11-21
CmpDate: 2024-11-21
Classical cadherins evolutionary constraints in primates is associated with their expression in the central nervous system.
PloS one, 19(11):e0313428 pii:PONE-D-24-25424.
Classical cadherins (CDH) comprise a family of single-pass transmembrane glycoproteins that contribute to tissue morphogenesis by regulating cell-cell adhesion, cytoskeletal dynamics, and cell signaling. CDH are grouped into type I (CDH 1, 2, 3, 4 and 15) and type II (CDH 5, 6, 7, 8, 9, 10, 11, 12, 18, 20, 22 and 24), based on the folding of the cadherin binding domain involved in trans-dimer formation. CDH are exclusively found in metazoans, and the origin and expansion of the gene family coincide with the emergence of multicellularity and vertebrates respectively. This study examined the evolutionary changes of CDH orthologs in primates and the factors that influence selective pressure to investigate the varying constraints exerted among CDH. Pairwise comparisons of the number of amino acid substitutions and of the ratio of non-synonymous substitutions per non-synonymous sites (dN) over synonymous substitutions per synonymous sites (dS), show that CDH2, CDH4, and most type II CDH have been under significantly higher negative selective pressure as compared to CDH1, CDH3, CDH5 and CDH19. Evaluation of gene essentiality as determined by the effect of germline deletion on animal viability, morphogenic phenotype, and reproductive fitness, show no correlation with the with extent of negative selection observed on CDH. Spearman's correlation analysis shows a positive correlation between CDH expression levels (E) in mouse and human tissues and their rate of evolution (R), as observed in most proteins expressed on the cell surface. However, CDH expression in the CNS show a significant E-R negative correlation, indicating that the strong negative selection exerted on CDH2, CDH4, and most type II CDH is associated with their expression in the CNS. CDH participate in a variety of cellular processes in the CNS including neuronal migration and functional assembly of neural circuits, which could profoundly influence animal fitness. Therefore, our findings suggest that the unusually high negative selective pressure exerted on CDH2, CDH4 and most type II CDH is due to their role in CNS formation and function and may have contributed to shape the evolution of the CNS in primates.
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@article {pmid39570883,
year = {2024},
author = {Petersen, M and Reyes-Vigil, F and Campo, M and Brusés, JL},
title = {Classical cadherins evolutionary constraints in primates is associated with their expression in the central nervous system.},
journal = {PloS one},
volume = {19},
number = {11},
pages = {e0313428},
doi = {10.1371/journal.pone.0313428},
pmid = {39570883},
issn = {1932-6203},
mesh = {Animals ; *Cadherins/genetics/metabolism ; *Primates/genetics ; *Evolution, Molecular ; Mice ; *Central Nervous System/metabolism ; Humans ; Phylogeny ; Selection, Genetic ; },
abstract = {Classical cadherins (CDH) comprise a family of single-pass transmembrane glycoproteins that contribute to tissue morphogenesis by regulating cell-cell adhesion, cytoskeletal dynamics, and cell signaling. CDH are grouped into type I (CDH 1, 2, 3, 4 and 15) and type II (CDH 5, 6, 7, 8, 9, 10, 11, 12, 18, 20, 22 and 24), based on the folding of the cadherin binding domain involved in trans-dimer formation. CDH are exclusively found in metazoans, and the origin and expansion of the gene family coincide with the emergence of multicellularity and vertebrates respectively. This study examined the evolutionary changes of CDH orthologs in primates and the factors that influence selective pressure to investigate the varying constraints exerted among CDH. Pairwise comparisons of the number of amino acid substitutions and of the ratio of non-synonymous substitutions per non-synonymous sites (dN) over synonymous substitutions per synonymous sites (dS), show that CDH2, CDH4, and most type II CDH have been under significantly higher negative selective pressure as compared to CDH1, CDH3, CDH5 and CDH19. Evaluation of gene essentiality as determined by the effect of germline deletion on animal viability, morphogenic phenotype, and reproductive fitness, show no correlation with the with extent of negative selection observed on CDH. Spearman's correlation analysis shows a positive correlation between CDH expression levels (E) in mouse and human tissues and their rate of evolution (R), as observed in most proteins expressed on the cell surface. However, CDH expression in the CNS show a significant E-R negative correlation, indicating that the strong negative selection exerted on CDH2, CDH4, and most type II CDH is associated with their expression in the CNS. CDH participate in a variety of cellular processes in the CNS including neuronal migration and functional assembly of neural circuits, which could profoundly influence animal fitness. Therefore, our findings suggest that the unusually high negative selective pressure exerted on CDH2, CDH4 and most type II CDH is due to their role in CNS formation and function and may have contributed to shape the evolution of the CNS in primates.},
}
MeSH Terms:
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hide MeSH Terms
Animals
*Cadherins/genetics/metabolism
*Primates/genetics
*Evolution, Molecular
Mice
*Central Nervous System/metabolism
Humans
Phylogeny
Selection, Genetic
RevDate: 2024-11-19
CmpDate: 2024-11-19
Control of sporophyte secondary cell wall development in Marchantia by a Class II KNOX gene.
Current biology : CB, 34(22):5213-5222.e5.
Land plants evolved from an ancestral alga around 470 mya, evolving complex multicellularity in both haploid gametophyte and diploid sporophyte generations. The evolution of water-conducting tissues in the sporophyte generation was crucial for the success of land plants, paving the way for the colonization of a variety of terrestrial habitats. Class II KNOX (KNOX2) genes are major regulators of secondary cell wall formation and seed mucilage (pectin) deposition in flowering plants. Here, we show that, in the liverwort Marchantia polymorpha, loss-of-function alleles of the KNOX2 ortholog, MpKNOX2, or its dimerization partner, MpBELL1, have defects in capsule wall secondary cell wall and spore pectin biosynthesis. Both genes are expressed in the gametophytic calyptra surrounding the sporophyte and exert maternal effects, suggesting intergenerational regulation from the maternal gametophyte to the sporophytic embryo. These findings also suggest the presence of a secondary wall genetic program in the non-vascular liverwort capsule wall, with attributes of secondary walls in vascular tissues.
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@article {pmid39447574,
year = {2024},
author = {Dierschke, T and Levins, J and Lampugnani, ER and Ebert, B and Zachgo, S and Bowman, JL},
title = {Control of sporophyte secondary cell wall development in Marchantia by a Class II KNOX gene.},
journal = {Current biology : CB},
volume = {34},
number = {22},
pages = {5213-5222.e5},
doi = {10.1016/j.cub.2024.09.061},
pmid = {39447574},
issn = {1879-0445},
mesh = {*Cell Wall/metabolism/genetics ; *Marchantia/genetics/growth & development ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; Germ Cells, Plant/growth & development/metabolism ; },
abstract = {Land plants evolved from an ancestral alga around 470 mya, evolving complex multicellularity in both haploid gametophyte and diploid sporophyte generations. The evolution of water-conducting tissues in the sporophyte generation was crucial for the success of land plants, paving the way for the colonization of a variety of terrestrial habitats. Class II KNOX (KNOX2) genes are major regulators of secondary cell wall formation and seed mucilage (pectin) deposition in flowering plants. Here, we show that, in the liverwort Marchantia polymorpha, loss-of-function alleles of the KNOX2 ortholog, MpKNOX2, or its dimerization partner, MpBELL1, have defects in capsule wall secondary cell wall and spore pectin biosynthesis. Both genes are expressed in the gametophytic calyptra surrounding the sporophyte and exert maternal effects, suggesting intergenerational regulation from the maternal gametophyte to the sporophytic embryo. These findings also suggest the presence of a secondary wall genetic program in the non-vascular liverwort capsule wall, with attributes of secondary walls in vascular tissues.},
}
MeSH Terms:
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*Cell Wall/metabolism/genetics
*Marchantia/genetics/growth & development
*Plant Proteins/genetics/metabolism
Gene Expression Regulation, Plant
Germ Cells, Plant/growth & development/metabolism
RevDate: 2024-11-16
CmpDate: 2024-11-15
The emergence of Sox and POU transcription factors predates the origins of animal stem cells.
Nature communications, 15(1):9868.
Stem cells are a hallmark of animal multicellularity. Sox and POU transcription factors are associated with stemness and were believed to be animal innovations, reported absent in their unicellular relatives. Here we describe unicellular Sox and POU factors. Choanoflagellate and filasterean Sox proteins have DNA-binding specificity similar to mammalian Sox2. Choanoflagellate-but not filasterean-Sox can replace Sox2 to reprogram mouse somatic cells into induced pluripotent stem cells (iPSCs) through interacting with the mouse POU member Oct4. In contrast, choanoflagellate POU has a distinct DNA-binding profile and cannot generate iPSCs. Ancestrally reconstructed Sox proteins indicate that iPSC formation capacity is pervasive among resurrected sequences, thus loss of Sox2-like properties fostered Sox family subfunctionalization. Our findings imply that the evolution of animal stem cells might have involved the exaptation of a pre-existing set of transcription factors, where pre-animal Sox was biochemically similar to extant Sox, whilst POU factors required evolutionary innovations.
Additional Links: PMID-39543096
PubMed:
Citation:
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@article {pmid39543096,
year = {2024},
author = {Gao, Y and Tan, DS and Girbig, M and Hu, H and Zhou, X and Xie, Q and Yeung, SW and Lee, KS and Ho, SY and Cojocaru, V and Yan, J and Hochberg, GKA and de Mendoza, A and Jauch, R},
title = {The emergence of Sox and POU transcription factors predates the origins of animal stem cells.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {9868},
pmid = {39543096},
issn = {2041-1723},
support = {C7064-22G//Research Grants Council, University Grants Committee (RGC, UGC)/ ; },
mesh = {Animals ; Mice ; *SOX Transcription Factors/metabolism/genetics ; *Induced Pluripotent Stem Cells/metabolism/cytology ; *SOXB1 Transcription Factors/metabolism/genetics ; POU Domain Factors/metabolism/genetics ; Octamer Transcription Factor-3/metabolism/genetics ; Humans ; Evolution, Molecular ; Phylogeny ; Stem Cells/metabolism/cytology ; Cellular Reprogramming/genetics ; },
abstract = {Stem cells are a hallmark of animal multicellularity. Sox and POU transcription factors are associated with stemness and were believed to be animal innovations, reported absent in their unicellular relatives. Here we describe unicellular Sox and POU factors. Choanoflagellate and filasterean Sox proteins have DNA-binding specificity similar to mammalian Sox2. Choanoflagellate-but not filasterean-Sox can replace Sox2 to reprogram mouse somatic cells into induced pluripotent stem cells (iPSCs) through interacting with the mouse POU member Oct4. In contrast, choanoflagellate POU has a distinct DNA-binding profile and cannot generate iPSCs. Ancestrally reconstructed Sox proteins indicate that iPSC formation capacity is pervasive among resurrected sequences, thus loss of Sox2-like properties fostered Sox family subfunctionalization. Our findings imply that the evolution of animal stem cells might have involved the exaptation of a pre-existing set of transcription factors, where pre-animal Sox was biochemically similar to extant Sox, whilst POU factors required evolutionary innovations.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
Mice
*SOX Transcription Factors/metabolism/genetics
*Induced Pluripotent Stem Cells/metabolism/cytology
*SOXB1 Transcription Factors/metabolism/genetics
POU Domain Factors/metabolism/genetics
Octamer Transcription Factor-3/metabolism/genetics
Humans
Evolution, Molecular
Phylogeny
Stem Cells/metabolism/cytology
Cellular Reprogramming/genetics
RevDate: 2024-11-13
CmpDate: 2024-11-13
Distinct evolutionary trajectories following loss of RNA interference in Cryptococcus neoformans.
Proceedings of the National Academy of Sciences of the United States of America, 121(47):e2416656121.
While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates that rapidly develop drug resistance due to transposition of a retrotransposon, Cnl1. Cnl1-mediated hypermutation is caused by a nonsense mutation in a gene encoding an RNA interference (RNAi) component, ZNF3, combined with a tremendous transposon burden. To elucidate adaptive mechanisms following RNAi loss, two bioinformatic pipelines were developed to identify RNAi loss-of-function (LOF) mutations in a collection of 387 sequenced C. neoformans isolates. Remarkably, several RNAi-loss isolates were identified that are not hypermutators and have not accumulated transposons. To test whether these RNAi LOF mutations can cause hypermutation, the mutations were introduced into a nonhypermutator strain with a high transposon burden, which resulted in a hypermutator phenotype. To further investigate whether RNAi-loss isolates can become hypermutators, in vitro passaging was performed. Although no hypermutators were found in two C. neoformans RNAi-loss strains after short-term passage, hypermutation was observed in a passaged Cryptococcus deneoformans strain with an increased transposon burden. Consistent with a two-step evolution, when an RNAi-loss isolate was crossed with an isolate containing a high Cnl1 burden, F1 hypermutator progeny inheriting a high transposon burden were identified. In addition to Cnl1 transpositions, insertions of a gigantic DNA transposon KDZ1 (~11 kb) contributed to hypermutation in the progeny. Our results suggest that RNAi loss is relatively common (7/387, ~1.8%) and enables distinct evolutionary trajectories: hypermutation following transposon accumulation or survival without hypermutation.
Additional Links: PMID-39536081
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PubMed:
Citation:
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@article {pmid39536081,
year = {2024},
author = {Huang, J and Larmore, CJ and Priest, SJ and Xu, Z and Dietrich, FS and Yadav, V and Magwene, PM and Sun, S and Heitman, J},
title = {Distinct evolutionary trajectories following loss of RNA interference in Cryptococcus neoformans.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {47},
pages = {e2416656121},
doi = {10.1073/pnas.2416656121},
pmid = {39536081},
issn = {1091-6490},
support = {AI039115-27//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI050113-20//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI133654-07//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI133654-07//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {*Cryptococcus neoformans/genetics ; *RNA Interference ; Evolution, Molecular ; DNA Transposable Elements/genetics ; Retroelements/genetics ; Fungal Proteins/genetics/metabolism ; Loss of Function Mutation ; Mutation ; Drug Resistance, Fungal/genetics ; },
abstract = {While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates that rapidly develop drug resistance due to transposition of a retrotransposon, Cnl1. Cnl1-mediated hypermutation is caused by a nonsense mutation in a gene encoding an RNA interference (RNAi) component, ZNF3, combined with a tremendous transposon burden. To elucidate adaptive mechanisms following RNAi loss, two bioinformatic pipelines were developed to identify RNAi loss-of-function (LOF) mutations in a collection of 387 sequenced C. neoformans isolates. Remarkably, several RNAi-loss isolates were identified that are not hypermutators and have not accumulated transposons. To test whether these RNAi LOF mutations can cause hypermutation, the mutations were introduced into a nonhypermutator strain with a high transposon burden, which resulted in a hypermutator phenotype. To further investigate whether RNAi-loss isolates can become hypermutators, in vitro passaging was performed. Although no hypermutators were found in two C. neoformans RNAi-loss strains after short-term passage, hypermutation was observed in a passaged Cryptococcus deneoformans strain with an increased transposon burden. Consistent with a two-step evolution, when an RNAi-loss isolate was crossed with an isolate containing a high Cnl1 burden, F1 hypermutator progeny inheriting a high transposon burden were identified. In addition to Cnl1 transpositions, insertions of a gigantic DNA transposon KDZ1 (~11 kb) contributed to hypermutation in the progeny. Our results suggest that RNAi loss is relatively common (7/387, ~1.8%) and enables distinct evolutionary trajectories: hypermutation following transposon accumulation or survival without hypermutation.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Cryptococcus neoformans/genetics
*RNA Interference
Evolution, Molecular
DNA Transposable Elements/genetics
Retroelements/genetics
Fungal Proteins/genetics/metabolism
Loss of Function Mutation
Mutation
Drug Resistance, Fungal/genetics
RevDate: 2024-11-07
CmpDate: 2024-11-07
The bioenergetic cost of building a metazoan.
Proceedings of the National Academy of Sciences of the United States of America, 121(46):e2414742121.
All life forms depend on the conversion of energy into biomass used in growth and reproduction. For unicellular heterotrophs, the energetic cost associated with building a cell scales slightly sublinearly with cell weight. However, observations on multiple Daphnia species and numerous other metazoans suggest that although a similar size-specific scaling is retained in multicellular heterotrophs, there is a quantum leap in the energy required to build a replacement soma, presumably owing to the added investment in nonproductive features such as cell adhesion, support tissue, and intercellular communication and transport. Thus, any context-dependent ecological advantages that accompany the evolution of multicellularity come at a high baseline bioenergetic cost. At the phylogenetic level, for both unicellular and multicellular eukaryotes, the energetic expense per unit biomass produced declines with increasing adult size of a species, but there is a countergradient scaling within the developmental trajectories of individual metazoan species, with the cost of biomass production increasing with size. Translation of the results into the universal currency of adenosine triphosphate (ATP) hydrolyses provides insight into the demands on the electron-transport/ATP-synthase machinery per organism and on the minimum doubling times for biomass production imposed by the costs of duplicating the energy-producing infrastructure.
Additional Links: PMID-39508768
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PubMed:
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@article {pmid39508768,
year = {2024},
author = {Lynch, M},
title = {The bioenergetic cost of building a metazoan.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {46},
pages = {e2414742121},
doi = {10.1073/pnas.2414742121},
pmid = {39508768},
issn = {1091-6490},
support = {BSR 83-06072//NSF | BIO | Division of Environmental Biology (DEB)/ ; BSR 89-11038//NSF | BIO | Division of Environmental Biology (DEB)/ ; DBI-2119963//NSF | BIO | Division of Environmental Biology (DEB)/ ; IOS-1922914//NSF | BIO | Division of Integrative Organismal Systems (IOS)/ ; 2R35GM122566//HHS | National Institutes of Health (NIH)/ ; 735927//Gordon and Betty Moore Foundation (GBMF)/ ; },
mesh = {Animals ; *Energy Metabolism ; *Adenosine Triphosphate/metabolism ; *Biomass ; Daphnia/growth & development/metabolism/physiology ; Phylogeny ; },
abstract = {All life forms depend on the conversion of energy into biomass used in growth and reproduction. For unicellular heterotrophs, the energetic cost associated with building a cell scales slightly sublinearly with cell weight. However, observations on multiple Daphnia species and numerous other metazoans suggest that although a similar size-specific scaling is retained in multicellular heterotrophs, there is a quantum leap in the energy required to build a replacement soma, presumably owing to the added investment in nonproductive features such as cell adhesion, support tissue, and intercellular communication and transport. Thus, any context-dependent ecological advantages that accompany the evolution of multicellularity come at a high baseline bioenergetic cost. At the phylogenetic level, for both unicellular and multicellular eukaryotes, the energetic expense per unit biomass produced declines with increasing adult size of a species, but there is a countergradient scaling within the developmental trajectories of individual metazoan species, with the cost of biomass production increasing with size. Translation of the results into the universal currency of adenosine triphosphate (ATP) hydrolyses provides insight into the demands on the electron-transport/ATP-synthase machinery per organism and on the minimum doubling times for biomass production imposed by the costs of duplicating the energy-producing infrastructure.},
}
MeSH Terms:
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hide MeSH Terms
Animals
*Energy Metabolism
*Adenosine Triphosphate/metabolism
*Biomass
Daphnia/growth & development/metabolism/physiology
Phylogeny
RevDate: 2024-11-13
CmpDate: 2024-11-13
A multicellular developmental program in a close animal relative.
Nature, 635(8038):382-389.
All animals develop from a single-celled zygote into a complex multicellular organism through a series of precisely orchestrated processes[1,2]. Despite the remarkable conservation of early embryogenesis across animals, the evolutionary origins of how and when this process first emerged remain elusive. Here, by combining time-resolved imaging and transcriptomic profiling, we show that single cells of the ichthyosporean Chromosphaera perkinsii-a close relative that diverged from animals about 1 billion years ago[3,4]-undergo symmetry breaking and develop through cleavage divisions to produce a prolonged multicellular colony with distinct co-existing cell types. Our findings about the autonomous and palintomic developmental program of C. perkinsii hint that such multicellular development either is much older than previously thought or evolved convergently in ichthyosporeans.
Additional Links: PMID-39506108
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Citation:
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@article {pmid39506108,
year = {2024},
author = {Olivetta, M and Bhickta, C and Chiaruttini, N and Burns, J and Dudin, O},
title = {A multicellular developmental program in a close animal relative.},
journal = {Nature},
volume = {635},
number = {8038},
pages = {382-389},
pmid = {39506108},
issn = {1476-4687},
mesh = {*Single-Cell Analysis ; Eukaryota/cytology/genetics ; Animals ; Transcriptome ; Gene Expression Profiling ; Biological Evolution ; Embryonic Development ; },
abstract = {All animals develop from a single-celled zygote into a complex multicellular organism through a series of precisely orchestrated processes[1,2]. Despite the remarkable conservation of early embryogenesis across animals, the evolutionary origins of how and when this process first emerged remain elusive. Here, by combining time-resolved imaging and transcriptomic profiling, we show that single cells of the ichthyosporean Chromosphaera perkinsii-a close relative that diverged from animals about 1 billion years ago[3,4]-undergo symmetry breaking and develop through cleavage divisions to produce a prolonged multicellular colony with distinct co-existing cell types. Our findings about the autonomous and palintomic developmental program of C. perkinsii hint that such multicellular development either is much older than previously thought or evolved convergently in ichthyosporeans.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Single-Cell Analysis
Eukaryota/cytology/genetics
Animals
Transcriptome
Gene Expression Profiling
Biological Evolution
Embryonic Development
RevDate: 2024-11-09
CmpDate: 2024-11-07
Repeated horizontal acquisition of lagriamide-producing symbionts in Lagriinae beetles.
The ISME journal, 18(1):.
Microbial symbionts associate with multicellular organisms on a continuum from facultative associations to mutual codependency. In the oldest intracellular symbioses there is exclusive vertical symbiont transmission, and co-diversification of symbiotic partners over millions of years. Such symbionts often undergo genome reduction due to low effective population sizes, frequent population bottlenecks, and reduced purifying selection. Here, we describe multiple independent acquisition events of closely related defensive symbionts followed by genome erosion in a group of Lagriinae beetles. Previous work in Lagria villosa revealed the dominant genome-eroded symbiont of the genus Burkholderia produces the antifungal compound lagriamide, protecting the beetle's eggs and larvae from antagonistic fungi. Here, we use metagenomics to assemble 11 additional genomes of lagriamide-producing symbionts from 7 different host species within Lagriinae from 5 countries, to unravel the evolutionary history of this symbiotic relationship. In each host, we detected one dominant genome-eroded Burkholderia symbiont encoding the lagriamide biosynthetic gene cluster. However, we did not find evidence for host-symbiont co-diversification or for monophyly of the lagriamide-producing symbionts. Instead, our analyses support a single ancestral acquisition of the gene cluster followed by at least four independent symbiont acquisitions and subsequent genome erosion in each lineage. By contrast, a clade of plant-associated relatives retained large genomes but secondarily lost the lagriamide gene cluster. Our results, therefore, reveal a dynamic evolutionary history with multiple independent symbiont acquisitions characterized by a high degree of specificity and highlight the importance of the specialized metabolite lagriamide for the establishment and maintenance of this defensive symbiosis.
Additional Links: PMID-39441990
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@article {pmid39441990,
year = {2024},
author = {Uppal, S and Waterworth, SC and Nick, A and Vogel, H and Flórez, LV and Kaltenpoth, M and Kwan, JC},
title = {Repeated horizontal acquisition of lagriamide-producing symbionts in Lagriinae beetles.},
journal = {The ISME journal},
volume = {18},
number = {1},
pages = {},
pmid = {39441990},
issn = {1751-7370},
support = {ERC CoG 819585//European Research Council through an ERC Consolidator/ ; 1845890//National Science Foundation/ ; },
mesh = {Animals ; *Symbiosis ; *Coleoptera/microbiology ; *Burkholderia/genetics/metabolism/classification/physiology ; Phylogeny ; Metagenomics ; Genome, Bacterial ; Gene Transfer, Horizontal ; },
abstract = {Microbial symbionts associate with multicellular organisms on a continuum from facultative associations to mutual codependency. In the oldest intracellular symbioses there is exclusive vertical symbiont transmission, and co-diversification of symbiotic partners over millions of years. Such symbionts often undergo genome reduction due to low effective population sizes, frequent population bottlenecks, and reduced purifying selection. Here, we describe multiple independent acquisition events of closely related defensive symbionts followed by genome erosion in a group of Lagriinae beetles. Previous work in Lagria villosa revealed the dominant genome-eroded symbiont of the genus Burkholderia produces the antifungal compound lagriamide, protecting the beetle's eggs and larvae from antagonistic fungi. Here, we use metagenomics to assemble 11 additional genomes of lagriamide-producing symbionts from 7 different host species within Lagriinae from 5 countries, to unravel the evolutionary history of this symbiotic relationship. In each host, we detected one dominant genome-eroded Burkholderia symbiont encoding the lagriamide biosynthetic gene cluster. However, we did not find evidence for host-symbiont co-diversification or for monophyly of the lagriamide-producing symbionts. Instead, our analyses support a single ancestral acquisition of the gene cluster followed by at least four independent symbiont acquisitions and subsequent genome erosion in each lineage. By contrast, a clade of plant-associated relatives retained large genomes but secondarily lost the lagriamide gene cluster. Our results, therefore, reveal a dynamic evolutionary history with multiple independent symbiont acquisitions characterized by a high degree of specificity and highlight the importance of the specialized metabolite lagriamide for the establishment and maintenance of this defensive symbiosis.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Symbiosis
*Coleoptera/microbiology
*Burkholderia/genetics/metabolism/classification/physiology
Phylogeny
Metagenomics
Genome, Bacterial
Gene Transfer, Horizontal
RevDate: 2024-11-08
CmpDate: 2024-11-08
A new motile animal with implications for the evolution of axial polarity from the Ediacaran of South Australia.
Evolution & development, 26(6):e12491.
Fossils of the Ediacara Biota preserve the oldest evidence for complex, macroscopic animals. Most are difficult to constrain phylogenetically, however, the presence of rare, derived groups suggests that many more fossils from this period represent extant groups than are currently appreciated. One approach to recognize such early animals is to instead focus on characteristics widespread in animals today, for example multicellularity, motility, and axial polarity. Here, we describe a new taxon, Quaestio simpsonorum gen. et sp. nov. from the Ediacaran of South Australia. Quaestio is reconstructed with a thin external membrane connecting more resilient tissues with anterior-posterior polarity, left-right asymmetry and tentative evidence for dorsoventral differentiation. Associated trace fossils indicate an epibenthic and motile lifestyle. Our results suggest that Quaestio was a motile eumetazoan with a body plan not previously recognized in the Ediacaran, including definitive evidence of chirality. This organization, combined with previous evidence for axial patterning in a variety of other Ediacara taxa, demonstrates that metazoan body plans were well established in the Precambrian.
Additional Links: PMID-39228078
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PubMed:
Citation:
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@article {pmid39228078,
year = {2024},
author = {Evans, SD and Hughes, IV and Hughes, EB and Dzaugis, PW and Dzaugis, MP and Gehling, JG and García-Bellido, DC and Droser, ML},
title = {A new motile animal with implications for the evolution of axial polarity from the Ediacaran of South Australia.},
journal = {Evolution & development},
volume = {26},
number = {6},
pages = {e12491},
doi = {10.1111/ede.12491},
pmid = {39228078},
issn = {1525-142X},
support = {//Australian Research Council/ ; //Agouron Institute/ ; /NASA/NASA/United States ; 80NSSC19K0472//NASA Exobiology/ ; DP22010277//Agouron Geobiology Fellowship/ ; DP22010277//Australian Research Council Discovery Project/ ; /NASA/NASA/United States ; },
mesh = {Animals ; *Fossils/anatomy & histology ; South Australia ; *Biological Evolution ; Body Patterning ; Phylogeny ; },
abstract = {Fossils of the Ediacara Biota preserve the oldest evidence for complex, macroscopic animals. Most are difficult to constrain phylogenetically, however, the presence of rare, derived groups suggests that many more fossils from this period represent extant groups than are currently appreciated. One approach to recognize such early animals is to instead focus on characteristics widespread in animals today, for example multicellularity, motility, and axial polarity. Here, we describe a new taxon, Quaestio simpsonorum gen. et sp. nov. from the Ediacaran of South Australia. Quaestio is reconstructed with a thin external membrane connecting more resilient tissues with anterior-posterior polarity, left-right asymmetry and tentative evidence for dorsoventral differentiation. Associated trace fossils indicate an epibenthic and motile lifestyle. Our results suggest that Quaestio was a motile eumetazoan with a body plan not previously recognized in the Ediacaran, including definitive evidence of chirality. This organization, combined with previous evidence for axial patterning in a variety of other Ediacara taxa, demonstrates that metazoan body plans were well established in the Precambrian.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Fossils/anatomy & histology
South Australia
*Biological Evolution
Body Patterning
Phylogeny
RevDate: 2024-11-07
CmpDate: 2024-11-07
Plant ribosomes as a score to fathom the melody of 2'-O-methylation across evolution.
RNA biology, 21(1):70-81.
2'-O-ribose methylation (2'-O-Me) is one of the most common RNA modifications detected in ribosomal RNAs (rRNA) from bacteria to eukaryotic cells. 2'-O-Me favours a specific RNA conformation and protects RNA from hydrolysis. Moreover, rRNA 2'-O-Me might stabilize its interactions with messenger RNA (mRNA), transfer RNA (tRNA) or proteins. The extent of rRNA 2'-O-Me fluctuates between species from 3-4 sites in bacteria to tens of sites in archaea, yeast, algae, plants and human. Depending on the organism as well as the rRNA targeting site and position, the 2'-O-Me reaction can be carried out by several site-specific RNA methyltransferases (RMTase) or by a single RMTase associated to specific RNA guides. Here, we review current progresses in rRNA 2'-O-Me (sites/Nm and RMTases) in plants and compare the results with molecular clues from unicellular (bacteria, archaea, algae and yeast) as well as multicellular (human and plants) organisms.
Additional Links: PMID-39508203
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PubMed:
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@article {pmid39508203,
year = {2024},
author = {Neumann, SA and Gaspin, C and Sáez-Vásquez, J},
title = {Plant ribosomes as a score to fathom the melody of 2'-O-methylation across evolution.},
journal = {RNA biology},
volume = {21},
number = {1},
pages = {70-81},
doi = {10.1080/15476286.2024.2417152},
pmid = {39508203},
issn = {1555-8584},
mesh = {Methylation ; *Ribosomes/metabolism ; *RNA, Ribosomal/metabolism/genetics/chemistry ; *Plants/metabolism/genetics ; Humans ; Evolution, Molecular ; Methyltransferases/metabolism/genetics/chemistry ; RNA, Plant/metabolism/genetics/chemistry ; Archaea/genetics/metabolism ; RNA, Transfer/metabolism/genetics/chemistry ; },
abstract = {2'-O-ribose methylation (2'-O-Me) is one of the most common RNA modifications detected in ribosomal RNAs (rRNA) from bacteria to eukaryotic cells. 2'-O-Me favours a specific RNA conformation and protects RNA from hydrolysis. Moreover, rRNA 2'-O-Me might stabilize its interactions with messenger RNA (mRNA), transfer RNA (tRNA) or proteins. The extent of rRNA 2'-O-Me fluctuates between species from 3-4 sites in bacteria to tens of sites in archaea, yeast, algae, plants and human. Depending on the organism as well as the rRNA targeting site and position, the 2'-O-Me reaction can be carried out by several site-specific RNA methyltransferases (RMTase) or by a single RMTase associated to specific RNA guides. Here, we review current progresses in rRNA 2'-O-Me (sites/Nm and RMTases) in plants and compare the results with molecular clues from unicellular (bacteria, archaea, algae and yeast) as well as multicellular (human and plants) organisms.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Methylation
*Ribosomes/metabolism
*RNA, Ribosomal/metabolism/genetics/chemistry
*Plants/metabolism/genetics
Humans
Evolution, Molecular
Methyltransferases/metabolism/genetics/chemistry
RNA, Plant/metabolism/genetics/chemistry
Archaea/genetics/metabolism
RNA, Transfer/metabolism/genetics/chemistry
RevDate: 2024-11-04
CmpDate: 2024-11-04
Deciphering the topological landscape of glioma using a network theory framework.
Scientific reports, 14(1):26724.
Glioma stem cells have been recognized as key players in glioma recurrence and therapeutic resistance, presenting a promising target for novel treatments. However, the limited understanding of the role glioma stem cells play in the glioma hierarchy has drawn controversy and hindered research translation into therapies. Despite significant advances in our understanding of gene regulatory networks, the dynamics of these networks and their implications for glioma remain elusive. This study employs a systemic theoretical perspective to integrate experimental knowledge into a core endogenous network model for glioma, thereby elucidating its energy landscape through network dynamics computation. The model identifies two stable states corresponding to astrocytic-like and oligodendrocytic-like tumor cells, connected by a transition state with the feature of high stemness, which serves as one of the energy barriers between astrocytic-like and oligodendrocytic-like states, indicating the instability of glioma stem cells in vivo. We also obtained various stable states further supporting glioma's multicellular origins and uncovered a group of transition states that could potentially induce tumor heterogeneity and therapeutic resistance. This research proposes that the transition states linking both glioma stable states are central to glioma heterogeneity and therapy resistance. Our approach may contribute to the advancement of glioma therapy by offering a novel perspective on the complex landscape of glioma biology.
Additional Links: PMID-39496747
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Citation:
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@article {pmid39496747,
year = {2024},
author = {Yao, M and Su, Y and Xiong, R and Zhang, X and Zhu, X and Chen, YC and Ao, P},
title = {Deciphering the topological landscape of glioma using a network theory framework.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {26724},
pmid = {39496747},
issn = {2045-2322},
support = {16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; },
mesh = {*Glioma/pathology/genetics/metabolism ; Humans ; *Gene Regulatory Networks ; *Neoplastic Stem Cells/metabolism/pathology ; *Brain Neoplasms/pathology/metabolism ; Gene Expression Regulation, Neoplastic ; Astrocytes/metabolism ; },
abstract = {Glioma stem cells have been recognized as key players in glioma recurrence and therapeutic resistance, presenting a promising target for novel treatments. However, the limited understanding of the role glioma stem cells play in the glioma hierarchy has drawn controversy and hindered research translation into therapies. Despite significant advances in our understanding of gene regulatory networks, the dynamics of these networks and their implications for glioma remain elusive. This study employs a systemic theoretical perspective to integrate experimental knowledge into a core endogenous network model for glioma, thereby elucidating its energy landscape through network dynamics computation. The model identifies two stable states corresponding to astrocytic-like and oligodendrocytic-like tumor cells, connected by a transition state with the feature of high stemness, which serves as one of the energy barriers between astrocytic-like and oligodendrocytic-like states, indicating the instability of glioma stem cells in vivo. We also obtained various stable states further supporting glioma's multicellular origins and uncovered a group of transition states that could potentially induce tumor heterogeneity and therapeutic resistance. This research proposes that the transition states linking both glioma stable states are central to glioma heterogeneity and therapy resistance. Our approach may contribute to the advancement of glioma therapy by offering a novel perspective on the complex landscape of glioma biology.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Glioma/pathology/genetics/metabolism
Humans
*Gene Regulatory Networks
*Neoplastic Stem Cells/metabolism/pathology
*Brain Neoplasms/pathology/metabolism
Gene Expression Regulation, Neoplastic
Astrocytes/metabolism
RevDate: 2024-10-31
CmpDate: 2024-10-31
The evolutionarily conserved PhLP3 is essential for sperm development in Drosophila melanogaster.
PloS one, 19(10):e0306676 pii:PONE-D-24-25002.
Phosducin-like proteins (PhLP) are thioredoxin domain-containing proteins that are highly conserved across unicellular and multicellular organisms. PhLP family proteins are hypothesized to function as co-chaperones in the folding of cytoskeletal proteins. Here, we present the initial molecular, biochemical, and functional characterization of CG4511 as Drosophila melanogaster PhLP3. We cloned the gene into a bacterial expression vector and produced enzymatically active recombinant PhLP3, which showed similar kinetics to previously characterized orthologues. A fly strain homozygous for a P-element insertion in the 5' UTR of the PhLP3 gene exhibited significant downregulation of PhLP3 expression. We found these male flies to be sterile. Microscopic analysis revealed altered testes morphology and impairment of spermiogenesis, leading to a lack of mature sperm. Among the most significant observations was the lack of actin cones during sperm maturation. Excision of the P-element insertion in PhLP3 restored male fertility, spermiogenesis, and seminal vesicle size. Given the high level of conservation of PhLP3, our data suggests PhLP3 may be an important regulator of sperm development across species.
Additional Links: PMID-39480878
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@article {pmid39480878,
year = {2024},
author = {Petit, C and Kojak, E and Webster, S and Marra, M and Sweeney, B and Chaikin, C and Jemc, JC and Kanzok, SM},
title = {The evolutionarily conserved PhLP3 is essential for sperm development in Drosophila melanogaster.},
journal = {PloS one},
volume = {19},
number = {10},
pages = {e0306676},
doi = {10.1371/journal.pone.0306676},
pmid = {39480878},
issn = {1932-6203},
mesh = {Animals ; *Drosophila melanogaster/genetics/metabolism/growth & development ; Male ; *Drosophila Proteins/genetics/metabolism ; *Spermatogenesis/genetics ; *Spermatozoa/metabolism ; Evolution, Molecular ; Testis/metabolism ; Conserved Sequence ; },
abstract = {Phosducin-like proteins (PhLP) are thioredoxin domain-containing proteins that are highly conserved across unicellular and multicellular organisms. PhLP family proteins are hypothesized to function as co-chaperones in the folding of cytoskeletal proteins. Here, we present the initial molecular, biochemical, and functional characterization of CG4511 as Drosophila melanogaster PhLP3. We cloned the gene into a bacterial expression vector and produced enzymatically active recombinant PhLP3, which showed similar kinetics to previously characterized orthologues. A fly strain homozygous for a P-element insertion in the 5' UTR of the PhLP3 gene exhibited significant downregulation of PhLP3 expression. We found these male flies to be sterile. Microscopic analysis revealed altered testes morphology and impairment of spermiogenesis, leading to a lack of mature sperm. Among the most significant observations was the lack of actin cones during sperm maturation. Excision of the P-element insertion in PhLP3 restored male fertility, spermiogenesis, and seminal vesicle size. Given the high level of conservation of PhLP3, our data suggests PhLP3 may be an important regulator of sperm development across species.},
}
MeSH Terms:
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hide MeSH Terms
Animals
*Drosophila melanogaster/genetics/metabolism/growth & development
Male
*Drosophila Proteins/genetics/metabolism
*Spermatogenesis/genetics
*Spermatozoa/metabolism
Evolution, Molecular
Testis/metabolism
Conserved Sequence
RevDate: 2024-10-30
CmpDate: 2024-10-30
Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution.
Molecular biology and evolution, 41(10):.
Understanding the main determinants of protein evolution is a fundamental challenge in biology. Despite many decades of active research, the molecular and cellular mechanisms underlying the substantial variability of evolutionary rates across cellular proteins are not currently well understood. It also remains unclear how protein molecular function is optimized in the context of multicellular species and why many proteins, such as enzymes, are only moderately efficient on average. Our analysis of genomics and functional datasets reveals in multiple organisms a strong inverse relationship between the optimality of protein molecular function and the rate of protein evolution. Furthermore, we find that highly expressed proteins tend to be substantially more functionally optimized. These results suggest that cellular expression costs lead to more pronounced functional optimization of abundant proteins and that the purifying selection to maintain high levels of functional optimality significantly slows protein evolution. We observe that in multicellular species both the rate of protein evolution and the degree of protein functional efficiency are primarily affected by expression in several distinct cell types and tissues, specifically, in developed neurons with upregulated synaptic processes in animals and in young and fast-growing tissues in plants. Overall, our analysis reveals how various constraints from the molecular, cellular, and species' levels of biological organization jointly affect the rate of protein evolution and the level of protein functional adaptation.
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@article {pmid39431545,
year = {2024},
author = {Usmanova, DR and Plata, G and Vitkup, D},
title = {Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution.},
journal = {Molecular biology and evolution},
volume = {41},
number = {10},
pages = {},
pmid = {39431545},
issn = {1537-1719},
support = {R35GM131884/GM/NIGMS NIH HHS/United States ; },
mesh = {*Evolution, Molecular ; Animals ; Proteins/genetics/metabolism ; Humans ; },
abstract = {Understanding the main determinants of protein evolution is a fundamental challenge in biology. Despite many decades of active research, the molecular and cellular mechanisms underlying the substantial variability of evolutionary rates across cellular proteins are not currently well understood. It also remains unclear how protein molecular function is optimized in the context of multicellular species and why many proteins, such as enzymes, are only moderately efficient on average. Our analysis of genomics and functional datasets reveals in multiple organisms a strong inverse relationship between the optimality of protein molecular function and the rate of protein evolution. Furthermore, we find that highly expressed proteins tend to be substantially more functionally optimized. These results suggest that cellular expression costs lead to more pronounced functional optimization of abundant proteins and that the purifying selection to maintain high levels of functional optimality significantly slows protein evolution. We observe that in multicellular species both the rate of protein evolution and the degree of protein functional efficiency are primarily affected by expression in several distinct cell types and tissues, specifically, in developed neurons with upregulated synaptic processes in animals and in young and fast-growing tissues in plants. Overall, our analysis reveals how various constraints from the molecular, cellular, and species' levels of biological organization jointly affect the rate of protein evolution and the level of protein functional adaptation.},
}
MeSH Terms:
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*Evolution, Molecular
Animals
Proteins/genetics/metabolism
Humans
RevDate: 2024-10-29
CmpDate: 2024-10-29
A novel 3D cardiac microtissue model for investigation of cardiovascular complications in rheumatoid arthritis.
Stem cell research & therapy, 15(1):382.
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects not only the joints but also has significant cardiovascular (CV) manifestations. The mechanistic interplay between RA and cardiovascular complications is not yet well understood due to the lack of relevant in vitro models. In this study, we established RA cardiac microtisses (cMTs) from iPSC-derived cardiomyocytes (CMs), endothelial cells (ECs) and cardiac fibroblasts (CFs) to investigate whether this fully human 3D multicellular system could serve as a platform to elucidate the connection between RA and CV disorders.
METHODS: PBMC and FLS from healthy and RA donors were reprogrammed to hiPSCs with Sendai vectors. hiPSCs pluripotency was assessed by IF, FACS, spontaneous embryoid bodies formation and teratoma assay. hiPSCs were differentiated to cardiac derivatives such as CMs, ECs and CFs, followed by cell markers characterizations (IF, FACS, qRT-PCR) and functional assessments. 3D cMTs were generated by aggregation of 70% CMs, 15% ECs and 15% CFs. After 21 days in culture, structural and metabolic properties of 3D cMTs were examined by IF, qRT-PCR and Seahorse bioanalyzer.
RESULTS: hiPSCs demonstrated typical colony-like morphology, normal karyotype, presence of pluripotency markers, and ability to differentiate into cells originating from all three germ layers. hiPSC-CMs showed spontaneous beating and expression of cardiac markers (cTnT, MYL7, NKX2.5, MYH7). hiPSC-ECs formed sprouting spheres and tubes and expressed CD31 and CD144. hiPSC-CFs presented spindle-shaped morphology and expression of vimentin, collagen 1 and DDR2. Self-aggregation of CMs/ECs/CFs allowed development of contracting 3D cMTs, demonstrating spherical organization of the cells, which partially resembled the cardiac muscle, both in structure and function. IF analysis confirmed the expression of cTnT, CD31, CD144 and DDR2 in generated 3D cMTs. RA cMTs exhibited significantly greater formation of capillary-like structures, mimicking enhanced vascularization-key RA feature-compared to control cMTs. Seahorse examination of cMTs revealed changes in mitochondrial and glycolytic rates in the presence of metabolic substrates and inhibitors.
CONCLUSIONS: The cMTs model may represent an advanced human stem cell-based platform for modeling CV complications in RA. The highly developed capillary-like structures observed within RA cMTs highlight a critical feature of inflammation-induced CV dysfunction in chronic inflammatory diseases.
Additional Links: PMID-39468575
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@article {pmid39468575,
year = {2024},
author = {Wolnik, J and Adamska, P and Oleksy, A and Sanetra, AM and Palus-Chramiec, K and Lewandowski, MH and Dulak, J and Biniecka, M},
title = {A novel 3D cardiac microtissue model for investigation of cardiovascular complications in rheumatoid arthritis.},
journal = {Stem cell research & therapy},
volume = {15},
number = {1},
pages = {382},
pmid = {39468575},
issn = {1757-6512},
support = {UMO-2017/25/B/NZ5/02243//Narodowe Centrum Nauki/ ; },
mesh = {Humans ; *Arthritis, Rheumatoid/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism/cytology ; *Myocytes, Cardiac/metabolism/pathology/cytology ; *Cell Differentiation ; *Fibroblasts/metabolism/pathology ; Cardiovascular Diseases/pathology/metabolism ; Endothelial Cells/metabolism/pathology ; Cells, Cultured ; },
abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects not only the joints but also has significant cardiovascular (CV) manifestations. The mechanistic interplay between RA and cardiovascular complications is not yet well understood due to the lack of relevant in vitro models. In this study, we established RA cardiac microtisses (cMTs) from iPSC-derived cardiomyocytes (CMs), endothelial cells (ECs) and cardiac fibroblasts (CFs) to investigate whether this fully human 3D multicellular system could serve as a platform to elucidate the connection between RA and CV disorders.
METHODS: PBMC and FLS from healthy and RA donors were reprogrammed to hiPSCs with Sendai vectors. hiPSCs pluripotency was assessed by IF, FACS, spontaneous embryoid bodies formation and teratoma assay. hiPSCs were differentiated to cardiac derivatives such as CMs, ECs and CFs, followed by cell markers characterizations (IF, FACS, qRT-PCR) and functional assessments. 3D cMTs were generated by aggregation of 70% CMs, 15% ECs and 15% CFs. After 21 days in culture, structural and metabolic properties of 3D cMTs were examined by IF, qRT-PCR and Seahorse bioanalyzer.
RESULTS: hiPSCs demonstrated typical colony-like morphology, normal karyotype, presence of pluripotency markers, and ability to differentiate into cells originating from all three germ layers. hiPSC-CMs showed spontaneous beating and expression of cardiac markers (cTnT, MYL7, NKX2.5, MYH7). hiPSC-ECs formed sprouting spheres and tubes and expressed CD31 and CD144. hiPSC-CFs presented spindle-shaped morphology and expression of vimentin, collagen 1 and DDR2. Self-aggregation of CMs/ECs/CFs allowed development of contracting 3D cMTs, demonstrating spherical organization of the cells, which partially resembled the cardiac muscle, both in structure and function. IF analysis confirmed the expression of cTnT, CD31, CD144 and DDR2 in generated 3D cMTs. RA cMTs exhibited significantly greater formation of capillary-like structures, mimicking enhanced vascularization-key RA feature-compared to control cMTs. Seahorse examination of cMTs revealed changes in mitochondrial and glycolytic rates in the presence of metabolic substrates and inhibitors.
CONCLUSIONS: The cMTs model may represent an advanced human stem cell-based platform for modeling CV complications in RA. The highly developed capillary-like structures observed within RA cMTs highlight a critical feature of inflammation-induced CV dysfunction in chronic inflammatory diseases.},
}
MeSH Terms:
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Humans
*Arthritis, Rheumatoid/metabolism/pathology
*Induced Pluripotent Stem Cells/metabolism/cytology
*Myocytes, Cardiac/metabolism/pathology/cytology
*Cell Differentiation
*Fibroblasts/metabolism/pathology
Cardiovascular Diseases/pathology/metabolism
Endothelial Cells/metabolism/pathology
Cells, Cultured
RevDate: 2024-10-28
CmpDate: 2024-10-28
Back to the future - 20 years of progress and developments in photonic microscopy and biological imaging.
Journal of cell science, 137(20):.
In 2023, the ImaBio consortium (imabio-cnrs.fr), an interdisciplinary life microscopy research group at the Centre National de la Recherche Scientifique, celebrated its 20th anniversary. ImaBio contributes to the biological imaging community through organization of MiFoBio conferences, which are interdisciplinary conferences featuring lectures and hands-on workshops that attract specialists from around the world. MiFoBio conferences provide the community with an opportunity to reflect on the evolution of the field, and the 2023 event offered retrospective talks discussing the past 20 years of topics in microscopy, including imaging of multicellular assemblies, image analysis, quantification of molecular motions and interactions within cells, advancements in fluorescent labels, and laser technology for multiphoton and label-free imaging of thick biological samples. In this Perspective, we compile summaries of these presentations overviewing 20 years of advancements in a specific area of microscopy, each of which concludes with a brief look towards the future. The full presentations are available on the ImaBio YouTube channel (youtube.com/@gdrimabio5724).
Additional Links: PMID-39465534
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@article {pmid39465534,
year = {2024},
author = {Erard, M and Favard, C and Lavis, LD and Recher, G and Rigneault, H and Sage, D},
title = {Back to the future - 20 years of progress and developments in photonic microscopy and biological imaging.},
journal = {Journal of cell science},
volume = {137},
number = {20},
pages = {},
doi = {10.1242/jcs.262344},
pmid = {39465534},
issn = {1477-9137},
mesh = {Humans ; *Microscopy/methods/trends/instrumentation ; Animals ; Photons ; },
abstract = {In 2023, the ImaBio consortium (imabio-cnrs.fr), an interdisciplinary life microscopy research group at the Centre National de la Recherche Scientifique, celebrated its 20th anniversary. ImaBio contributes to the biological imaging community through organization of MiFoBio conferences, which are interdisciplinary conferences featuring lectures and hands-on workshops that attract specialists from around the world. MiFoBio conferences provide the community with an opportunity to reflect on the evolution of the field, and the 2023 event offered retrospective talks discussing the past 20 years of topics in microscopy, including imaging of multicellular assemblies, image analysis, quantification of molecular motions and interactions within cells, advancements in fluorescent labels, and laser technology for multiphoton and label-free imaging of thick biological samples. In this Perspective, we compile summaries of these presentations overviewing 20 years of advancements in a specific area of microscopy, each of which concludes with a brief look towards the future. The full presentations are available on the ImaBio YouTube channel (youtube.com/@gdrimabio5724).},
}
MeSH Terms:
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Humans
*Microscopy/methods/trends/instrumentation
Animals
Photons
RevDate: 2024-10-24
The Unknown within the Known: Nucleolus, Understudied Compartment in the Filamentous Fungi.
Mycobiology, 52(4):214-221.
Nucleolus is the most conspicuous sub-nuclear compartment that is well known as the site of RNA polymerase I-mediated rDNA transcription and assembly of ribosome subunits in eukaryotes. Recent studies on mammalian cells suggest that functions of nucleolus are not limited to ribosome biogenesis, and that nucleolus is involved in a diverse array of nuclear and cellular processes such as DNA repair, stress responses, and protein sequestration. In fungi, knowledge of nucleolus and its functions was primarily gleaned from the budding yeast. However, little is known about nucleolus of the filamentous fungi. Considering that the filamentous fungi are multi-cellular eukaryotes and thus distinct from the yeast in many aspects, researches on nucleoli of filamentous fungi would have the potential to uncover the evolution of nucleolus and its roles in the diverse cellular processes. Here we provide a brief up-to-date overview of nucleolus in general, and evidence suggesting their roles in fungal physiology and development.
Additional Links: PMID-39445133
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@article {pmid39445133,
year = {2024},
author = {Lee, SH and Dubey, N and Jeon, J},
title = {The Unknown within the Known: Nucleolus, Understudied Compartment in the Filamentous Fungi.},
journal = {Mycobiology},
volume = {52},
number = {4},
pages = {214-221},
pmid = {39445133},
issn = {1229-8093},
abstract = {Nucleolus is the most conspicuous sub-nuclear compartment that is well known as the site of RNA polymerase I-mediated rDNA transcription and assembly of ribosome subunits in eukaryotes. Recent studies on mammalian cells suggest that functions of nucleolus are not limited to ribosome biogenesis, and that nucleolus is involved in a diverse array of nuclear and cellular processes such as DNA repair, stress responses, and protein sequestration. In fungi, knowledge of nucleolus and its functions was primarily gleaned from the budding yeast. However, little is known about nucleolus of the filamentous fungi. Considering that the filamentous fungi are multi-cellular eukaryotes and thus distinct from the yeast in many aspects, researches on nucleoli of filamentous fungi would have the potential to uncover the evolution of nucleolus and its roles in the diverse cellular processes. Here we provide a brief up-to-date overview of nucleolus in general, and evidence suggesting their roles in fungal physiology and development.},
}
RevDate: 2024-10-24
A transcriptomic hourglass in brown algae.
Nature [Epub ahead of print].
Complex multicellularity has emerged independently across a few eukaryotic lineages and is often associated with the rise of elaborate, tightly coordinated developmental processes[1,2]. How multicellularity and development are interconnected in evolution is a major question in biology. The hourglass model of embryonic evolution depicts how developmental processes are conserved during evolution, and predicts morphological and molecular divergence in early and late embryogenesis, bridged by a conserved mid-embryonic (phylotypic) period linked to the formation of the basic body plan[3,4]. Initially found in animal embryos[5-8], molecular hourglass patterns have recently been proposed for land plants and fungi[9,10]. However, whether the hourglass pattern is an intrinsic feature of all complex multicellular eukaryotes remains unknown. Here we tested the presence of a molecular hourglass in the brown algae, a eukaryotic lineage that has evolved multicellularity independently from animals, fungi and plants[1,11,12]. By exploring transcriptome evolution patterns of brown algae with distinct morphological complexities, we uncovered an hourglass pattern during embryogenesis in morphologically complex species. Filamentous algae without canonical embryogenesis display transcriptome conservation in multicellular stages of the life cycle, whereas unicellular stages are more rapidly evolving. Our findings suggest that transcriptome conservation in brown algae is associated with cell differentiation stages, but is not necessarily linked to embryogenesis. Together with previous work in animals, plants and fungi, we provide further evidence for the generality of a developmental hourglass pattern across complex multicellular eukaryotes.
Additional Links: PMID-39443791
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@article {pmid39443791,
year = {2024},
author = {Lotharukpong, JS and Zheng, M and Luthringer, R and Liesner, D and Drost, HG and Coelho, SM},
title = {A transcriptomic hourglass in brown algae.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {39443791},
issn = {1476-4687},
abstract = {Complex multicellularity has emerged independently across a few eukaryotic lineages and is often associated with the rise of elaborate, tightly coordinated developmental processes[1,2]. How multicellularity and development are interconnected in evolution is a major question in biology. The hourglass model of embryonic evolution depicts how developmental processes are conserved during evolution, and predicts morphological and molecular divergence in early and late embryogenesis, bridged by a conserved mid-embryonic (phylotypic) period linked to the formation of the basic body plan[3,4]. Initially found in animal embryos[5-8], molecular hourglass patterns have recently been proposed for land plants and fungi[9,10]. However, whether the hourglass pattern is an intrinsic feature of all complex multicellular eukaryotes remains unknown. Here we tested the presence of a molecular hourglass in the brown algae, a eukaryotic lineage that has evolved multicellularity independently from animals, fungi and plants[1,11,12]. By exploring transcriptome evolution patterns of brown algae with distinct morphological complexities, we uncovered an hourglass pattern during embryogenesis in morphologically complex species. Filamentous algae without canonical embryogenesis display transcriptome conservation in multicellular stages of the life cycle, whereas unicellular stages are more rapidly evolving. Our findings suggest that transcriptome conservation in brown algae is associated with cell differentiation stages, but is not necessarily linked to embryogenesis. Together with previous work in animals, plants and fungi, we provide further evidence for the generality of a developmental hourglass pattern across complex multicellular eukaryotes.},
}
RevDate: 2024-10-10
Candidate genes involved in biosynthesis and degradation of the main extracellular matrix polysaccharides of brown algae and their probable evolutionary history.
BMC genomics, 25(1):950.
BACKGROUND: Brown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSPs), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data.
RESULTS: An extensive genomic dataset has been recently released for brown algae and their close sister species, for which we previously performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms. Here we provide a deeper analysis of this set of genes using comparative genomics, phylogenetics analyses, and protein modelling. Two key gene families involved in both the synthesis and degradation of alginate were suggested to have been acquired by the common ancestor of brown algae and their closest sister species Schizocladia ischiensis. Our analysis indicates that this assumption can be extended to additional metabolic steps, and thus to the whole alginate metabolic pathway. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we also investigate putative fucosyltransferase genes that may harbour a fucan synthase activity in brown algae.
CONCLUSIONS: Our analysis is the first extensive survey of carbohydrate-related enzymes in brown algae, and provides a valuable resource for future research into the glycome and ECM of brown algae. The expansion of specific families related to alginate metabolism may have represented an important prerequisite for the evolution of developmental complexity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon and in other Stramenopiles such as diatoms. Filling this knowledge gap in the future will help determine the origin and evolutionary history of fucan synthesis in eukaryotes.
Additional Links: PMID-39390408
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@article {pmid39390408,
year = {2024},
author = {Mazéas, L and Bouguerba-Collin, A and Cock, JM and Denoeud, F and Godfroy, O and Brillet-Guéguen, L and Barbeyron, T and Lipinska, AP and Delage, L and Corre, E and Drula, E and Henrissat, B and Czjzek, M and Terrapon, N and Hervé, C},
title = {Candidate genes involved in biosynthesis and degradation of the main extracellular matrix polysaccharides of brown algae and their probable evolutionary history.},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {950},
pmid = {39390408},
issn = {1471-2164},
support = {ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-10-INBS-09//Agence Nationale de la Recherche/ ; ANR-10-INBS-09//Agence Nationale de la Recherche/ ; ANR-11-INBS-0013//Agence Nationale de la Recherche/ ; ANR-11-INBS-0013//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-11-INBS-0013//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; 638240/ERC_/European Research Council/International ; },
abstract = {BACKGROUND: Brown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSPs), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data.
RESULTS: An extensive genomic dataset has been recently released for brown algae and their close sister species, for which we previously performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms. Here we provide a deeper analysis of this set of genes using comparative genomics, phylogenetics analyses, and protein modelling. Two key gene families involved in both the synthesis and degradation of alginate were suggested to have been acquired by the common ancestor of brown algae and their closest sister species Schizocladia ischiensis. Our analysis indicates that this assumption can be extended to additional metabolic steps, and thus to the whole alginate metabolic pathway. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we also investigate putative fucosyltransferase genes that may harbour a fucan synthase activity in brown algae.
CONCLUSIONS: Our analysis is the first extensive survey of carbohydrate-related enzymes in brown algae, and provides a valuable resource for future research into the glycome and ECM of brown algae. The expansion of specific families related to alginate metabolism may have represented an important prerequisite for the evolution of developmental complexity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon and in other Stramenopiles such as diatoms. Filling this knowledge gap in the future will help determine the origin and evolutionary history of fucan synthesis in eukaryotes.},
}
RevDate: 2024-10-09
CmpDate: 2024-10-09
Ecological principles for the evolution of communication in collective systems.
Proceedings. Biological sciences, 291(2032):20241562.
Communication allows members of a collective to share information about their environment. Advanced collective systems, such as multicellular organisms and social insect colonies, vary in whether they use communication at all and, if they do, in what types of signals they use, but the origins of these differences are poorly understood. Here, we develop a theoretical framework to investigate the evolution and diversity of communication strategies under collective-level selection. We find that whether communication can evolve depends on a collective's external environment: communication only evolves in sufficiently stable environments, where the costs of sensing are high enough to disfavour independent sensing but not so high that the optimal strategy is to ignore the environment altogether. Moreover, we find that the evolution of diverse signalling strategies-including those relying on prolonged signalling (e.g. honeybee waggle dance), persistence of signals in the environment (e.g. ant trail pheromones) and brief but frequent communicative interactions (e.g. ant antennal contacts)-can be explained theoretically in terms of the interplay between the demands of the environment and internal constraints on the signal. Altogether, we provide a general framework for comparing communication strategies found in nature and uncover simple ecological principles that may contribute to their diversity.
Additional Links: PMID-39381908
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@article {pmid39381908,
year = {2024},
author = {Staps, M and Tarnita, CE and Kawakatsu, M},
title = {Ecological principles for the evolution of communication in collective systems.},
journal = {Proceedings. Biological sciences},
volume = {291},
number = {2032},
pages = {20241562},
pmid = {39381908},
issn = {1471-2954},
support = {//James S. McDonnell Foundation/ ; },
mesh = {Animals ; *Animal Communication ; *Biological Evolution ; Bees/physiology ; Ants/physiology ; Models, Biological ; Social Behavior ; },
abstract = {Communication allows members of a collective to share information about their environment. Advanced collective systems, such as multicellular organisms and social insect colonies, vary in whether they use communication at all and, if they do, in what types of signals they use, but the origins of these differences are poorly understood. Here, we develop a theoretical framework to investigate the evolution and diversity of communication strategies under collective-level selection. We find that whether communication can evolve depends on a collective's external environment: communication only evolves in sufficiently stable environments, where the costs of sensing are high enough to disfavour independent sensing but not so high that the optimal strategy is to ignore the environment altogether. Moreover, we find that the evolution of diverse signalling strategies-including those relying on prolonged signalling (e.g. honeybee waggle dance), persistence of signals in the environment (e.g. ant trail pheromones) and brief but frequent communicative interactions (e.g. ant antennal contacts)-can be explained theoretically in terms of the interplay between the demands of the environment and internal constraints on the signal. Altogether, we provide a general framework for comparing communication strategies found in nature and uncover simple ecological principles that may contribute to their diversity.},
}
MeSH Terms:
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Animals
*Animal Communication
*Biological Evolution
Bees/physiology
Ants/physiology
Models, Biological
Social Behavior
RevDate: 2024-10-09
CmpDate: 2024-10-09
EnhancerNet: a predictive model of cell identity dynamics through enhancer selection.
Development (Cambridge, England), 151(19):.
Understanding how cell identity is encoded by the genome and acquired during differentiation is a central challenge in cell biology. I have developed a theoretical framework called EnhancerNet, which models the regulation of cell identity through the lens of transcription factor-enhancer interactions. I demonstrate that autoregulation in these interactions imposes a constraint on the model, resulting in simplified dynamics that can be parameterized from observed cell identities. Despite its simplicity, EnhancerNet recapitulates a broad range of experimental observations on cell identity dynamics, including enhancer selection, cell fate induction, hierarchical differentiation through multipotent progenitor states and direct reprogramming by transcription factor overexpression. The model makes specific quantitative predictions, reproducing known reprogramming recipes and the complex haematopoietic differentiation hierarchy without fitting unobserved parameters. EnhancerNet provides insights into how new cell types could evolve and highlights the functional importance of distal regulatory elements with dynamic chromatin in multicellular evolution.
Additional Links: PMID-39289870
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@article {pmid39289870,
year = {2024},
author = {Karin, O},
title = {EnhancerNet: a predictive model of cell identity dynamics through enhancer selection.},
journal = {Development (Cambridge, England)},
volume = {151},
number = {19},
pages = {},
doi = {10.1242/dev.202997},
pmid = {39289870},
issn = {1477-9129},
support = {//Imperial College London/ ; },
mesh = {*Enhancer Elements, Genetic/genetics ; *Cell Differentiation/genetics ; Animals ; *Transcription Factors/metabolism/genetics ; Chromatin/metabolism ; Cell Lineage/genetics ; Humans ; Models, Biological ; Models, Genetic ; },
abstract = {Understanding how cell identity is encoded by the genome and acquired during differentiation is a central challenge in cell biology. I have developed a theoretical framework called EnhancerNet, which models the regulation of cell identity through the lens of transcription factor-enhancer interactions. I demonstrate that autoregulation in these interactions imposes a constraint on the model, resulting in simplified dynamics that can be parameterized from observed cell identities. Despite its simplicity, EnhancerNet recapitulates a broad range of experimental observations on cell identity dynamics, including enhancer selection, cell fate induction, hierarchical differentiation through multipotent progenitor states and direct reprogramming by transcription factor overexpression. The model makes specific quantitative predictions, reproducing known reprogramming recipes and the complex haematopoietic differentiation hierarchy without fitting unobserved parameters. EnhancerNet provides insights into how new cell types could evolve and highlights the functional importance of distal regulatory elements with dynamic chromatin in multicellular evolution.},
}
MeSH Terms:
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*Enhancer Elements, Genetic/genetics
*Cell Differentiation/genetics
Animals
*Transcription Factors/metabolism/genetics
Chromatin/metabolism
Cell Lineage/genetics
Humans
Models, Biological
Models, Genetic
RevDate: 2024-10-08
CmpDate: 2024-10-08
Larger colony sizes favoured the evolution of more worker castes in ants.
Nature ecology & evolution, 8(10):1959-1971.
The size-complexity hypothesis is a leading explanation for the evolution of complex life on earth. It predicts that in lineages that have undergone a major transition in organismality, larger numbers of lower-level subunits select for increased division of labour. Current data from multicellular organisms and social insects support a positive correlation between the number of cells and number of cell types and between colony size and the number of castes. However, the implication of these results is unclear, because colony size and number of cells are correlated with other variables which may also influence selection for division of labour, and causality could be in either direction. Here, to resolve this problem, we tested multiple causal hypotheses using data from 794 ant species. We found that larger colony sizes favoured the evolution of increased division of labour, resulting in more worker castes and greater variation in worker size. By contrast, our results did not provide consistent support for alternative hypotheses regarding either queen mating frequency or number of queens per colony explaining variation in division of labour. Overall, our results provide strong support for the size-complexity hypothesis.
Additional Links: PMID-39187609
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@article {pmid39187609,
year = {2024},
author = {Bell-Roberts, L and Turner, JFR and Werner, GDA and Downing, PA and Ross, L and West, SA},
title = {Larger colony sizes favoured the evolution of more worker castes in ants.},
journal = {Nature ecology & evolution},
volume = {8},
number = {10},
pages = {1959-1971},
pmid = {39187609},
issn = {2397-334X},
support = {834164/ERC_/European Research Council/International ; 834164//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; BB/M011224/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; },
mesh = {*Ants/physiology ; Animals ; *Biological Evolution ; *Population Density ; Social Behavior ; },
abstract = {The size-complexity hypothesis is a leading explanation for the evolution of complex life on earth. It predicts that in lineages that have undergone a major transition in organismality, larger numbers of lower-level subunits select for increased division of labour. Current data from multicellular organisms and social insects support a positive correlation between the number of cells and number of cell types and between colony size and the number of castes. However, the implication of these results is unclear, because colony size and number of cells are correlated with other variables which may also influence selection for division of labour, and causality could be in either direction. Here, to resolve this problem, we tested multiple causal hypotheses using data from 794 ant species. We found that larger colony sizes favoured the evolution of increased division of labour, resulting in more worker castes and greater variation in worker size. By contrast, our results did not provide consistent support for alternative hypotheses regarding either queen mating frequency or number of queens per colony explaining variation in division of labour. Overall, our results provide strong support for the size-complexity hypothesis.},
}
MeSH Terms:
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*Ants/physiology
Animals
*Biological Evolution
*Population Density
Social Behavior
RevDate: 2024-10-08
Microtubule reorganization and quiescence: an intertwined relationship.
Physiology (Bethesda, Md.) [Epub ahead of print].
Quiescence is operationally defined as a reversible proliferation arrest. This cellular state is central for both organism development and homeostasis, its dysregulation causing many pathologies. The quiescent state encompasses very diverse cellular situations depending on the cell type and its environment. Further, quiescent cell properties evolve with time, a process that is thought to be at the origin of aging in multicellular organisms. Microtubules are found in all eukaryotes, and are essential for cell proliferation as they support chromosome segregation and intracellular trafficking. Upon proliferation cessation and quiescence establishment, the microtubule cytoskeleton was shown to undergo significant remodeling. The purpose of this review is to examine the literature in search of evidence to determine whether the observed microtubule reorganizations are merely a consequence of quiescence establishment or if they somehow participate in this cell fate decision.
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@article {pmid39378102,
year = {2024},
author = {Laporte, D and Sagot, I},
title = {Microtubule reorganization and quiescence: an intertwined relationship.},
journal = {Physiology (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1152/physiol.00036.2024},
pmid = {39378102},
issn = {1548-9221},
support = {ANR-21-CE13-0023-01//Agence Nationale de la Recherche (ANR)/ ; },
abstract = {Quiescence is operationally defined as a reversible proliferation arrest. This cellular state is central for both organism development and homeostasis, its dysregulation causing many pathologies. The quiescent state encompasses very diverse cellular situations depending on the cell type and its environment. Further, quiescent cell properties evolve with time, a process that is thought to be at the origin of aging in multicellular organisms. Microtubules are found in all eukaryotes, and are essential for cell proliferation as they support chromosome segregation and intracellular trafficking. Upon proliferation cessation and quiescence establishment, the microtubule cytoskeleton was shown to undergo significant remodeling. The purpose of this review is to examine the literature in search of evidence to determine whether the observed microtubule reorganizations are merely a consequence of quiescence establishment or if they somehow participate in this cell fate decision.},
}
RevDate: 2024-10-08
CmpDate: 2024-10-08
On the evolutionary developmental biology of the cell.
Trends in genetics : TIG, 40(10):822-833.
Organisms are complex assemblages of cells, cells that produce light, shoot harpoons, and secrete glue. Therefore, identifying the mechanisms that generate novelty at the level of the individual cell is essential for understanding how multicellular life evolves. For decades, the field of evolutionary developmental biology (Evo-Devo) has been developing a framework for connecting genetic variation that arises during embryonic development to the emergence of diverse adult forms. With increasing access to new single cell 'omics technologies and an array of techniques for manipulating gene expression, we can now extend these inquiries inward to the level of the individual cell. In this opinion, I argue that applying an Evo-Devo framework to single cells makes it possible to explore the natural history of cells, where this was once only possible at the organismal level.
Additional Links: PMID-38971670
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@article {pmid38971670,
year = {2024},
author = {Babonis, LS},
title = {On the evolutionary developmental biology of the cell.},
journal = {Trends in genetics : TIG},
volume = {40},
number = {10},
pages = {822-833},
doi = {10.1016/j.tig.2024.06.003},
pmid = {38971670},
issn = {0168-9525},
mesh = {*Developmental Biology ; *Biological Evolution ; Animals ; Humans ; Single-Cell Analysis/methods ; },
abstract = {Organisms are complex assemblages of cells, cells that produce light, shoot harpoons, and secrete glue. Therefore, identifying the mechanisms that generate novelty at the level of the individual cell is essential for understanding how multicellular life evolves. For decades, the field of evolutionary developmental biology (Evo-Devo) has been developing a framework for connecting genetic variation that arises during embryonic development to the emergence of diverse adult forms. With increasing access to new single cell 'omics technologies and an array of techniques for manipulating gene expression, we can now extend these inquiries inward to the level of the individual cell. In this opinion, I argue that applying an Evo-Devo framework to single cells makes it possible to explore the natural history of cells, where this was once only possible at the organismal level.},
}
MeSH Terms:
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*Developmental Biology
*Biological Evolution
Animals
Humans
Single-Cell Analysis/methods
RevDate: 2024-10-07
CmpDate: 2024-10-07
Molecular recording using DNA Typewriter.
Nature protocols, 19(10):2833-2862.
Recording molecular information to genomic DNA is a powerful means of investigating topics ranging from multicellular development to cancer evolution. With molecular recording based on genome editing, events such as cell divisions and signaling pathway activity drive specific alterations in a cell's DNA, marking the genome with information about a cell's history that can be read out after the fact. Although genome editing has been used for molecular recording, capturing the temporal relationships among recorded events in mammalian cells remains challenging. The DNA Typewriter system overcomes this limitation by leveraging prime editing to facilitate sequential insertions to an engineered genomic region. DNA Typewriter includes three distinct components: DNA Tape as the 'substrate' to which edits accrue in an ordered manner, the prime editor enzyme, and prime editing guide RNAs, which program insertional edits to DNA Tape. In this protocol, we describe general design considerations for DNA Typewriter, step-by-step instructions on how to perform recording experiments by using DNA Typewriter in HEK293T cells, and example scripts for analyzing DNA Typewriter data (https://doi.org/10.6084/m9.figshare.22728758). This protocol covers two main applications of DNA Typewriter: recording sequential transfection events with programmed barcode insertions by using prime editing and recording lineage information during the expansion of a single cell to many. Compared with other methods that are compatible with mammalian cells, DNA Typewriter enables the recording of temporal information with higher recording capacities and can be completed within 4-6 weeks with basic expertise in molecular cloning, mammalian cell culturing and DNA sequencing data analysis.
Additional Links: PMID-38844553
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@article {pmid38844553,
year = {2024},
author = {Liao, H and Choi, J and Shendure, J},
title = {Molecular recording using DNA Typewriter.},
journal = {Nature protocols},
volume = {19},
number = {10},
pages = {2833-2862},
pmid = {38844553},
issn = {1750-2799},
mesh = {Humans ; *DNA/genetics ; *Gene Editing/methods ; HEK293 Cells ; RNA, Guide, CRISPR-Cas Systems/genetics ; CRISPR-Cas Systems ; },
abstract = {Recording molecular information to genomic DNA is a powerful means of investigating topics ranging from multicellular development to cancer evolution. With molecular recording based on genome editing, events such as cell divisions and signaling pathway activity drive specific alterations in a cell's DNA, marking the genome with information about a cell's history that can be read out after the fact. Although genome editing has been used for molecular recording, capturing the temporal relationships among recorded events in mammalian cells remains challenging. The DNA Typewriter system overcomes this limitation by leveraging prime editing to facilitate sequential insertions to an engineered genomic region. DNA Typewriter includes three distinct components: DNA Tape as the 'substrate' to which edits accrue in an ordered manner, the prime editor enzyme, and prime editing guide RNAs, which program insertional edits to DNA Tape. In this protocol, we describe general design considerations for DNA Typewriter, step-by-step instructions on how to perform recording experiments by using DNA Typewriter in HEK293T cells, and example scripts for analyzing DNA Typewriter data (https://doi.org/10.6084/m9.figshare.22728758). This protocol covers two main applications of DNA Typewriter: recording sequential transfection events with programmed barcode insertions by using prime editing and recording lineage information during the expansion of a single cell to many. Compared with other methods that are compatible with mammalian cells, DNA Typewriter enables the recording of temporal information with higher recording capacities and can be completed within 4-6 weeks with basic expertise in molecular cloning, mammalian cell culturing and DNA sequencing data analysis.},
}
MeSH Terms:
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Humans
*DNA/genetics
*Gene Editing/methods
HEK293 Cells
RNA, Guide, CRISPR-Cas Systems/genetics
CRISPR-Cas Systems
RevDate: 2024-10-07
CmpDate: 2024-10-07
The evolution of multicellularity and cell differentiation symposium: bridging evolutionary cell biology and computational modelling using emerging model systems.
Biology open, 13(10):.
'The evolution of multicellularity and cell differentiation' symposium, organized as part of the EuroEvoDevo 2024 meeting on June 25-28th in Helsinki (Finland), addressed recent advances on the molecular and mechanistic basis for the evolution of multicellularity and cell differentiation in eukaryotes. The symposium involved over 100 participants and brought together 10 speakers at diverse career stages. Talks covered various topics at the interface of developmental biology, evolutionary cell biology, comparative genomics, computational biology, and ecology using animal, protist, algal and mathematical models. This symposium offered a unique opportunity for interdisciplinary dialog among researchers working on different systems, especially in promoting collaborations and aligning strategies for studying emerging model species. Moreover, it fostered opportunities to promote early career researchers in the field and opened discussions of ongoing work and unpublished results. In this Meeting Review, we aim to promote the research, capture the spirit of the meeting, and present key topics discussed within this dynamic, growing and open community.
Additional Links: PMID-39373528
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PubMed:
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@article {pmid39373528,
year = {2024},
author = {Ros-Rocher, N},
title = {The evolution of multicellularity and cell differentiation symposium: bridging evolutionary cell biology and computational modelling using emerging model systems.},
journal = {Biology open},
volume = {13},
number = {10},
pages = {},
doi = {10.1242/bio.061720},
pmid = {39373528},
issn = {2046-6390},
support = {101106415//European Union's Horizon Europe research and innovation funding program/ ; //Institute Pasteur: Institut Pasteur; Baylor College of Medicine/ ; },
mesh = {*Cell Differentiation/genetics ; *Biological Evolution ; Animals ; Computational Biology/methods ; Humans ; Cell Biology ; Models, Biological ; Computer Simulation ; Genomics/methods ; },
abstract = {'The evolution of multicellularity and cell differentiation' symposium, organized as part of the EuroEvoDevo 2024 meeting on June 25-28th in Helsinki (Finland), addressed recent advances on the molecular and mechanistic basis for the evolution of multicellularity and cell differentiation in eukaryotes. The symposium involved over 100 participants and brought together 10 speakers at diverse career stages. Talks covered various topics at the interface of developmental biology, evolutionary cell biology, comparative genomics, computational biology, and ecology using animal, protist, algal and mathematical models. This symposium offered a unique opportunity for interdisciplinary dialog among researchers working on different systems, especially in promoting collaborations and aligning strategies for studying emerging model species. Moreover, it fostered opportunities to promote early career researchers in the field and opened discussions of ongoing work and unpublished results. In this Meeting Review, we aim to promote the research, capture the spirit of the meeting, and present key topics discussed within this dynamic, growing and open community.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Cell Differentiation/genetics
*Biological Evolution
Animals
Computational Biology/methods
Humans
Cell Biology
Models, Biological
Computer Simulation
Genomics/methods
RevDate: 2024-10-03
CmpDate: 2024-09-20
Genome of Halimeda opuntia reveals differentiation of subgenomes and molecular bases of multinucleation and calcification in algae.
Proceedings of the National Academy of Sciences of the United States of America, 121(39):e2403222121.
Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated traits (e.g., rapid wound healing) are poorly understood. Here, we report the genome of Halimeda opuntia, a giant multinucleate unicellular chlorophyte characterized by interutricular calcification. We achieve a high-quality genome assembly that shows segregation into four subgenomes, with evidence for polyploidization concomitant with historical sea level and climate changes. We further find myosin VIII missing in H. opuntia and three other unicellular multinucleate chlorophytes, suggesting a potential mechanism that may underpin multinucleation. Genome analysis provides clues about how the unicellular alga could survive fragmentation and regenerate, as well as potential signatures for extracellular calcification and the coupling of calcification with photosynthesis. In addition, proteomic alkalinity shifts were found to potentially confer plasticity of H. opuntia to ocean acidification (OA). Our study provides crucial genetic information necessary for understanding multinucleation, cell regeneration, plasticity to OA, and different modes of calcification in algae and other organisms, which has important implications in reef conservation and bioengineering.
Additional Links: PMID-39302967
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@article {pmid39302967,
year = {2024},
author = {Zhang, H and Wang, X and Qu, M and Yu, H and Yin, J and Liu, X and Liu, Y and Zhang, B and Zhang, Y and Wei, Z and Yang, F and Wang, J and Shi, C and Fan, G and Sun, J and Long, L and Hutchins, DA and Bowler, C and Lin, S and Wang, D and Lin, Q},
title = {Genome of Halimeda opuntia reveals differentiation of subgenomes and molecular bases of multinucleation and calcification in algae.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {39},
pages = {e2403222121},
pmid = {39302967},
issn = {1091-6490},
support = {2022YFC3102403//the National Key Research and Development Programm of China/ ; 42230409//the National Natural Science Foundation of China/ ; 4980.01//the Gordon and Betty Moore Foundation/ ; 42030404//the National Natural Science Foundation of China/ ; 42076155//the National Natural Science Foundation of China/ ; 42425004//the National Natural Science Foundation of China/ ; },
mesh = {*Calcification, Physiologic/genetics ; Chlorophyta/genetics/metabolism ; Phylogeny ; Genome, Plant ; Photosynthesis/genetics ; },
abstract = {Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated traits (e.g., rapid wound healing) are poorly understood. Here, we report the genome of Halimeda opuntia, a giant multinucleate unicellular chlorophyte characterized by interutricular calcification. We achieve a high-quality genome assembly that shows segregation into four subgenomes, with evidence for polyploidization concomitant with historical sea level and climate changes. We further find myosin VIII missing in H. opuntia and three other unicellular multinucleate chlorophytes, suggesting a potential mechanism that may underpin multinucleation. Genome analysis provides clues about how the unicellular alga could survive fragmentation and regenerate, as well as potential signatures for extracellular calcification and the coupling of calcification with photosynthesis. In addition, proteomic alkalinity shifts were found to potentially confer plasticity of H. opuntia to ocean acidification (OA). Our study provides crucial genetic information necessary for understanding multinucleation, cell regeneration, plasticity to OA, and different modes of calcification in algae and other organisms, which has important implications in reef conservation and bioengineering.},
}
MeSH Terms:
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*Calcification, Physiologic/genetics
Chlorophyta/genetics/metabolism
Phylogeny
Genome, Plant
Photosynthesis/genetics
RevDate: 2024-09-21
CmpDate: 2024-09-14
Multicellularity and increasing Reynolds number impact on the evolutionary shift in flash-induced ciliary response in Volvocales.
BMC ecology and evolution, 24(1):119.
BACKGROUND: Volvocales in green algae have evolved by multicellularity of Chlamydomonas-like unicellular ancestor. Those with various cell numbers exist, such as unicellular Chlamydomonas, four-celled Tetrabaena, and Volvox species with different cell numbers (~1,000, ~5,000, and ~10,000). Each cell of these organisms shares two cilia and an eyespot, which are used for swimming and photosensing. They are all freshwater microalgae but inhabit different fluid environments: unicellular species live in low Reynolds-number (Re) environments where viscous forces dominate, whereas multicellular species live in relatively higher Re where inertial forces become non-negligible. Despite significant changes in the physical environment, during the evolution of multicellularity, they maintained photobehaviors (i.e., photoshock and phototactic responses), which allows them to survive under changing light conditions.
RESULTS: In this study, we utilized high-speed imaging to observe flash-induced changes in the ciliary beating manner of 27 Volvocales strains. We classified flash-induced ciliary responses in Volvocales into four patterns: "1: temporal waveform conversion", "2: no obvious response", "3: pause in ciliary beating", and "4: temporal changes in ciliary beating directions". We found that which species exhibit which pattern depends on Re, which is associated with the individual size of each species rather than phylogenetic relationships.
CONCLUSIONS: These results suggest that only organisms that acquired different patterns of ciliary responses survived the evolutionary transition to multicellularity with a greater number of cells while maintaining photobehaviors. This study highlights the significance of the Re as a selection pressure in evolution and offers insights for designing propulsion systems in biomimetic micromachines.
Additional Links: PMID-39277710
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Citation:
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@article {pmid39277710,
year = {2024},
author = {Ueki, N and Wakabayashi, KI},
title = {Multicellularity and increasing Reynolds number impact on the evolutionary shift in flash-induced ciliary response in Volvocales.},
journal = {BMC ecology and evolution},
volume = {24},
number = {1},
pages = {119},
pmid = {39277710},
issn = {2730-7182},
mesh = {*Cilia/physiology ; *Biological Evolution ; Chlorophyta/physiology/genetics ; Volvox/genetics/physiology ; Light ; },
abstract = {BACKGROUND: Volvocales in green algae have evolved by multicellularity of Chlamydomonas-like unicellular ancestor. Those with various cell numbers exist, such as unicellular Chlamydomonas, four-celled Tetrabaena, and Volvox species with different cell numbers (~1,000, ~5,000, and ~10,000). Each cell of these organisms shares two cilia and an eyespot, which are used for swimming and photosensing. They are all freshwater microalgae but inhabit different fluid environments: unicellular species live in low Reynolds-number (Re) environments where viscous forces dominate, whereas multicellular species live in relatively higher Re where inertial forces become non-negligible. Despite significant changes in the physical environment, during the evolution of multicellularity, they maintained photobehaviors (i.e., photoshock and phototactic responses), which allows them to survive under changing light conditions.
RESULTS: In this study, we utilized high-speed imaging to observe flash-induced changes in the ciliary beating manner of 27 Volvocales strains. We classified flash-induced ciliary responses in Volvocales into four patterns: "1: temporal waveform conversion", "2: no obvious response", "3: pause in ciliary beating", and "4: temporal changes in ciliary beating directions". We found that which species exhibit which pattern depends on Re, which is associated with the individual size of each species rather than phylogenetic relationships.
CONCLUSIONS: These results suggest that only organisms that acquired different patterns of ciliary responses survived the evolutionary transition to multicellularity with a greater number of cells while maintaining photobehaviors. This study highlights the significance of the Re as a selection pressure in evolution and offers insights for designing propulsion systems in biomimetic micromachines.},
}
MeSH Terms:
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*Cilia/physiology
*Biological Evolution
Chlorophyta/physiology/genetics
Volvox/genetics/physiology
Light
RevDate: 2024-09-16
CmpDate: 2024-09-14
The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.
International journal of molecular sciences, 25(17):.
If one must prioritize among the vast array of contributing factors to cancer evolution, environmental-stress-mediated chromosome instability (CIN) should easily surpass individual gene mutations. CIN leads to the emergence of genomically unstable life forms, enabling them to grow dominantly within the stable life form of the host. In contrast, stochastic gene mutations play a role in aiding the growth of the cancer population, with their importance depending on the initial emergence of the new system. Furthermore, many specific gene mutations among the many available can perform this function, decreasing the clinical value of any specific gene mutation. Since these unstable life forms can respond to treatment differently than stable ones, cancer often escapes from drug treatment by forming new systems, which leads to problems during the treatment for patients. To understand how diverse factors impact CIN-mediated macroevolution and genome integrity-ensured microevolution, the concept of two-phased cancer evolution is used to reconcile some major characteristics of cancer, such as bioenergetic, unicellular, and multicellular evolution. Specifically, the spiral of life function model is proposed, which integrates major historical evolutionary innovations and conservation with information management. Unlike normal organismal evolution in the microevolutionary phase, where a given species occupies a specific location within the spiral, cancer populations are highly heterogenous at multiple levels, including epigenetic levels. Individual cells occupy different levels and positions within the spiral, leading to supersystems of mixed cellular populations that exhibit both macro and microevolution. This analysis, utilizing karyotype to define the genetic networks of the cellular system and CIN to determine the instability of the system, as well as considering gene mutation and epigenetics as modifiers of the system for information amplification and usage, explores the high evolutionary potential of cancer. It provides a new, unified understanding of cancer as a supersystem, encouraging efforts to leverage the dynamics of CIN to develop improved treatment options. Moreover, it offers a historically contingent model for organismal evolution that reconciles the roles of both evolutionary innovation and conservation through macroevolution and microevolution, respectively.
Additional Links: PMID-39273111
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@article {pmid39273111,
year = {2024},
author = {Kasperski, A and Heng, HH},
title = {The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.},
journal = {International journal of molecular sciences},
volume = {25},
number = {17},
pages = {},
pmid = {39273111},
issn = {1422-0067},
mesh = {*Neoplasms/genetics ; Humans ; *Chromosomal Instability ; Biological Evolution ; Animals ; Mutation ; Evolution, Molecular ; Epigenesis, Genetic ; Genomic Instability ; },
abstract = {If one must prioritize among the vast array of contributing factors to cancer evolution, environmental-stress-mediated chromosome instability (CIN) should easily surpass individual gene mutations. CIN leads to the emergence of genomically unstable life forms, enabling them to grow dominantly within the stable life form of the host. In contrast, stochastic gene mutations play a role in aiding the growth of the cancer population, with their importance depending on the initial emergence of the new system. Furthermore, many specific gene mutations among the many available can perform this function, decreasing the clinical value of any specific gene mutation. Since these unstable life forms can respond to treatment differently than stable ones, cancer often escapes from drug treatment by forming new systems, which leads to problems during the treatment for patients. To understand how diverse factors impact CIN-mediated macroevolution and genome integrity-ensured microevolution, the concept of two-phased cancer evolution is used to reconcile some major characteristics of cancer, such as bioenergetic, unicellular, and multicellular evolution. Specifically, the spiral of life function model is proposed, which integrates major historical evolutionary innovations and conservation with information management. Unlike normal organismal evolution in the microevolutionary phase, where a given species occupies a specific location within the spiral, cancer populations are highly heterogenous at multiple levels, including epigenetic levels. Individual cells occupy different levels and positions within the spiral, leading to supersystems of mixed cellular populations that exhibit both macro and microevolution. This analysis, utilizing karyotype to define the genetic networks of the cellular system and CIN to determine the instability of the system, as well as considering gene mutation and epigenetics as modifiers of the system for information amplification and usage, explores the high evolutionary potential of cancer. It provides a new, unified understanding of cancer as a supersystem, encouraging efforts to leverage the dynamics of CIN to develop improved treatment options. Moreover, it offers a historically contingent model for organismal evolution that reconciles the roles of both evolutionary innovation and conservation through macroevolution and microevolution, respectively.},
}
MeSH Terms:
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hide MeSH Terms
*Neoplasms/genetics
Humans
*Chromosomal Instability
Biological Evolution
Animals
Mutation
Evolution, Molecular
Epigenesis, Genetic
Genomic Instability
RevDate: 2024-09-13
CmpDate: 2024-09-13
Current computational methods for spatial transcriptomics in cancer biology.
Advances in cancer research, 163:71-106.
Cells in multicellular organisms constitute a self-organizing society by interacting with their neighbors. Cancer originates from malfunction of cellular behavior in the context of such a self-organizing system. The identities or characteristics of individual tumor cells can be represented by the hallmark of gene expression or transcriptome, which can be addressed using single-cell dissociation followed by RNA sequencing. However, the dissociation process of single cells results in losing the cellular address in tissue or neighbor information of each tumor cell, which is critical to understanding the malfunctioning cellular behavior in the microenvironment. Spatial transcriptomics technology enables measuring the transcriptome which is tagged by the address within a tissue. However, to understand cellular behavior in a self-organizing society, we need to apply mathematical or statistical methods. Here, we provide a review on current computational methods for spatial transcriptomics in cancer biology.
Additional Links: PMID-39271268
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@article {pmid39271268,
year = {2024},
author = {Mo, J and Bae, J and Saqib, J and Hwang, D and Jin, Y and Park, B and Park, J and Kim, J},
title = {Current computational methods for spatial transcriptomics in cancer biology.},
journal = {Advances in cancer research},
volume = {163},
number = {},
pages = {71-106},
doi = {10.1016/bs.acr.2024.06.006},
pmid = {39271268},
issn = {2162-5557},
mesh = {Humans ; *Neoplasms/genetics/pathology ; *Transcriptome/genetics ; *Computational Biology/methods ; Gene Expression Profiling/methods ; Tumor Microenvironment/genetics ; Animals ; },
abstract = {Cells in multicellular organisms constitute a self-organizing society by interacting with their neighbors. Cancer originates from malfunction of cellular behavior in the context of such a self-organizing system. The identities or characteristics of individual tumor cells can be represented by the hallmark of gene expression or transcriptome, which can be addressed using single-cell dissociation followed by RNA sequencing. However, the dissociation process of single cells results in losing the cellular address in tissue or neighbor information of each tumor cell, which is critical to understanding the malfunctioning cellular behavior in the microenvironment. Spatial transcriptomics technology enables measuring the transcriptome which is tagged by the address within a tissue. However, to understand cellular behavior in a self-organizing society, we need to apply mathematical or statistical methods. Here, we provide a review on current computational methods for spatial transcriptomics in cancer biology.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Neoplasms/genetics/pathology
*Transcriptome/genetics
*Computational Biology/methods
Gene Expression Profiling/methods
Tumor Microenvironment/genetics
Animals
RevDate: 2024-09-20
CmpDate: 2024-09-20
Algorithms for Autonomous Formation of Multicellular Shapes from Single Cells.
ACS synthetic biology, 13(9):2753-2763.
Multicellular organisms originate from a single cell, ultimately giving rise to mature organisms of heterogeneous cell type composition in complex structures. Recent work in the areas of stem cell biology and tissue engineering has laid major groundwork in the ability to convert certain types of cells into other types, but there has been limited progress in the ability to control the morphology of cellular masses as they grow. Contemporary approaches to this problem have included the use of artificial scaffolds, 3D bioprinting, and complex media formulations; however, there are no existing approaches to controlling this process purely through genetics and from a single-cell starting point. Here we describe a computer-aided design approach, called CellArchitect, for designing recombinase-based genetic circuits for controlling the formation of multicellular masses into arbitrary shapes in human cells.
Additional Links: PMID-39194023
Publisher:
PubMed:
Citation:
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@article {pmid39194023,
year = {2024},
author = {Appleton, E and Mehdipour, N and Daifuku, T and Briers, D and Haghighi, I and Moret, M and Chao, G and Wannier, T and Chiappino-Pepe, A and Huang, J and Belta, C and Church, GM},
title = {Algorithms for Autonomous Formation of Multicellular Shapes from Single Cells.},
journal = {ACS synthetic biology},
volume = {13},
number = {9},
pages = {2753-2763},
doi = {10.1021/acssynbio.4c00037},
pmid = {39194023},
issn = {2161-5063},
mesh = {Humans ; *Algorithms ; Gene Regulatory Networks ; Single-Cell Analysis/methods ; Tissue Engineering/methods ; Computer-Aided Design ; Cell Shape ; },
abstract = {Multicellular organisms originate from a single cell, ultimately giving rise to mature organisms of heterogeneous cell type composition in complex structures. Recent work in the areas of stem cell biology and tissue engineering has laid major groundwork in the ability to convert certain types of cells into other types, but there has been limited progress in the ability to control the morphology of cellular masses as they grow. Contemporary approaches to this problem have included the use of artificial scaffolds, 3D bioprinting, and complex media formulations; however, there are no existing approaches to controlling this process purely through genetics and from a single-cell starting point. Here we describe a computer-aided design approach, called CellArchitect, for designing recombinase-based genetic circuits for controlling the formation of multicellular masses into arbitrary shapes in human cells.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Algorithms
Gene Regulatory Networks
Single-Cell Analysis/methods
Tissue Engineering/methods
Computer-Aided Design
Cell Shape
RevDate: 2024-08-25
CmpDate: 2024-08-23
TF-High-Evolutionary: In Vivo Mutagenesis of Gene Regulatory Networks for the Study of the Genetics and Evolution of the Drosophila Regulatory Genome.
Molecular biology and evolution, 41(8):.
Understanding the evolutionary potential of mutations in gene regulatory networks is essential to furthering the study of evolution and development. However, in multicellular systems, genetic manipulation of regulatory networks in a targeted and high-throughput way remains challenging. In this study, we designed TF-High-Evolutionary (HighEvo), a transcription factor (TF) fused with a base editor (activation-induced deaminase), to continuously induce germline mutations at TF-binding sites across regulatory networks in Drosophila. Populations of flies expressing TF-HighEvo in their germlines accumulated mutations at rates an order of magnitude higher than natural populations. Importantly, these mutations accumulated around the targeted TF-binding sites across the genome, leading to distinct morphological phenotypes consistent with the developmental roles of the tagged TFs. As such, this TF-HighEvo method allows the interrogation of the mutational space of gene regulatory networks at scale and can serve as a powerful reagent for experimental evolution and genetic screens focused on the regulatory genome.
Additional Links: PMID-39117360
PubMed:
Citation:
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@article {pmid39117360,
year = {2024},
author = {Li, XC and Srinivasan, V and Laiker, I and Misunou, N and Frankel, N and Pallares, LF and Crocker, J},
title = {TF-High-Evolutionary: In Vivo Mutagenesis of Gene Regulatory Networks for the Study of the Genetics and Evolution of the Drosophila Regulatory Genome.},
journal = {Molecular biology and evolution},
volume = {41},
number = {8},
pages = {},
pmid = {39117360},
issn = {1537-1719},
support = {//European Molecular Biology Laboratory Interdisciplinary Postdoc Programme/ ; //European Molecular Biology Laboratory/ ; //Max Planck Society/ ; },
mesh = {Animals ; *Gene Regulatory Networks ; *Transcription Factors/genetics/metabolism ; Genome, Insect ; Mutagenesis ; Drosophila/genetics ; Evolution, Molecular ; Drosophila melanogaster/genetics ; },
abstract = {Understanding the evolutionary potential of mutations in gene regulatory networks is essential to furthering the study of evolution and development. However, in multicellular systems, genetic manipulation of regulatory networks in a targeted and high-throughput way remains challenging. In this study, we designed TF-High-Evolutionary (HighEvo), a transcription factor (TF) fused with a base editor (activation-induced deaminase), to continuously induce germline mutations at TF-binding sites across regulatory networks in Drosophila. Populations of flies expressing TF-HighEvo in their germlines accumulated mutations at rates an order of magnitude higher than natural populations. Importantly, these mutations accumulated around the targeted TF-binding sites across the genome, leading to distinct morphological phenotypes consistent with the developmental roles of the tagged TFs. As such, this TF-HighEvo method allows the interrogation of the mutational space of gene regulatory networks at scale and can serve as a powerful reagent for experimental evolution and genetic screens focused on the regulatory genome.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Gene Regulatory Networks
*Transcription Factors/genetics/metabolism
Genome, Insect
Mutagenesis
Drosophila/genetics
Evolution, Molecular
Drosophila melanogaster/genetics
RevDate: 2024-07-27
CmpDate: 2024-07-28
Exploring the Function of Gene Promoter Regulatory Elements Using CRISPR Tools.
Methods in molecular biology (Clifton, N.J.), 2844:145-156.
Gene promoters serve as pivotal regulators of transcription, orchestrating the initiation, rate, and specificity of gene expression, resulting in cellular diversity found among distinct cell types within multicellular organisms. Identification of the sequence and function of promoters' regulatory elements and their complex interaction with transcription factors, enhancers, silencers, and insulators is fundamental to coordinated transcriptional processes within cells. Identifying these regulatory elements and scrutinizing their functions and interactions through the use of synthetic promoters can pave the way for researchers in various fields ranging from uncovering the origins of diseases associated with promoter mutations to harnessing these regulatory components in biotechnological applications.In this chapter, we describe the manipulation of regulatory elements within promoters, with a specific focus on the use of CRISPR technology on enhancers and silencer elements of the Ovalbumin gene promoter. We explain and discuss processes for the deletion of/interference with regulatory elements within the promoter, employing CRISPR-based approaches. Furthermore, we demonstrate that a CRISPR/Cas-manipulated promoter can activate gene transcription in cell types where it is normally inactive. This confirms that CRISPR technology can be effectively used to engineer synthetic promoters with desired characteristics, such as inducibility, tissue-specificity, or enhanced transcriptional strength. Such an approach provides valuable insights into the mechanisms and dynamics of gene expression, thereby offering new opportunities in the fields of biotechnology and medicine.
Additional Links: PMID-39068338
PubMed:
Citation:
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@article {pmid39068338,
year = {2024},
author = {Yousefi Taemeh, S and Dehdilani, N and Goshayeshi, L and Dehghani, H},
title = {Exploring the Function of Gene Promoter Regulatory Elements Using CRISPR Tools.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2844},
number = {},
pages = {145-156},
pmid = {39068338},
issn = {1940-6029},
mesh = {*Promoter Regions, Genetic ; *CRISPR-Cas Systems ; Animals ; Humans ; Gene Expression Regulation ; Enhancer Elements, Genetic ; Ovalbumin/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; },
abstract = {Gene promoters serve as pivotal regulators of transcription, orchestrating the initiation, rate, and specificity of gene expression, resulting in cellular diversity found among distinct cell types within multicellular organisms. Identification of the sequence and function of promoters' regulatory elements and their complex interaction with transcription factors, enhancers, silencers, and insulators is fundamental to coordinated transcriptional processes within cells. Identifying these regulatory elements and scrutinizing their functions and interactions through the use of synthetic promoters can pave the way for researchers in various fields ranging from uncovering the origins of diseases associated with promoter mutations to harnessing these regulatory components in biotechnological applications.In this chapter, we describe the manipulation of regulatory elements within promoters, with a specific focus on the use of CRISPR technology on enhancers and silencer elements of the Ovalbumin gene promoter. We explain and discuss processes for the deletion of/interference with regulatory elements within the promoter, employing CRISPR-based approaches. Furthermore, we demonstrate that a CRISPR/Cas-manipulated promoter can activate gene transcription in cell types where it is normally inactive. This confirms that CRISPR technology can be effectively used to engineer synthetic promoters with desired characteristics, such as inducibility, tissue-specificity, or enhanced transcriptional strength. Such an approach provides valuable insights into the mechanisms and dynamics of gene expression, thereby offering new opportunities in the fields of biotechnology and medicine.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Promoter Regions, Genetic
*CRISPR-Cas Systems
Animals
Humans
Gene Expression Regulation
Enhancer Elements, Genetic
Ovalbumin/genetics
Clustered Regularly Interspaced Short Palindromic Repeats/genetics
RevDate: 2024-10-02
CmpDate: 2024-10-02
Adaptive Cellular Radiations and the Genetic Mechanisms Underlying Animal Nervous System Diversification.
Annual review of cell and developmental biology, 40(1):407-425.
In animals, the nervous system evolved as the primary interface between multicellular organisms and the environment. As organisms became larger and more complex, the primary functions of the nervous system expanded to include the modulation and coordination of individual responsive cells via paracrine and synaptic functions as well as to monitor and maintain the organism's own internal environment. This was initially accomplished via paracrine signaling and eventually through the assembly of multicell circuits in some lineages. Cells with similar functions and centralized nervous systems have independently arisen in several lineages. We highlight the molecular mechanisms that underlie parallel diversifications of the nervous system.
Additional Links: PMID-39052757
Publisher:
PubMed:
Citation:
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@article {pmid39052757,
year = {2024},
author = {Hehmeyer, J and Plessier, F and Marlow, H},
title = {Adaptive Cellular Radiations and the Genetic Mechanisms Underlying Animal Nervous System Diversification.},
journal = {Annual review of cell and developmental biology},
volume = {40},
number = {1},
pages = {407-425},
doi = {10.1146/annurev-cellbio-111822-124041},
pmid = {39052757},
issn = {1530-8995},
mesh = {Animals ; *Nervous System/metabolism ; Biological Evolution ; Humans ; Signal Transduction/genetics ; },
abstract = {In animals, the nervous system evolved as the primary interface between multicellular organisms and the environment. As organisms became larger and more complex, the primary functions of the nervous system expanded to include the modulation and coordination of individual responsive cells via paracrine and synaptic functions as well as to monitor and maintain the organism's own internal environment. This was initially accomplished via paracrine signaling and eventually through the assembly of multicell circuits in some lineages. Cells with similar functions and centralized nervous systems have independently arisen in several lineages. We highlight the molecular mechanisms that underlie parallel diversifications of the nervous system.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Nervous System/metabolism
Biological Evolution
Humans
Signal Transduction/genetics
RevDate: 2024-07-16
CmpDate: 2024-07-15
Adaptation of SIVmac to baboon primary cells results in complete absence of in vivo baboon infectivity.
Frontiers in cellular and infection microbiology, 14:1408245.
While simian immunodeficiency virus (SIV) infection is non-pathogenic in naturally infected African nonhuman primate hosts, experimental or accidental infection in rhesus macaques often leads to AIDS. Baboons, widely distributed throughout Africa, do not naturally harbor SIV, and experimental infection of baboons with SIVmac results in transient low-level viral replication. Elucidation of mechanisms of natural immunity in baboons could uncover new targets of antiviral intervention. We tested the hypothesis that an SIVmac adapted to replicate in baboon primary cells will gain the capacity to establish chronic infections in vivo. Here, we generated SIVmac variants in baboon cells through serial passage in PBMC from different donors (SIVbn-PBMC s1), in PBMC from the same donors (SIVbn-PBMC s2), or in isolated CD4 cells from the same donors used for series 2 (SIVbn-CD4). While SIVbn-PBMC s1 and SIVbn-CD4 demonstrated increased replication capacity, SIVbn-PBMC s2 did not. Pharmacological blockade of CCR5 revealed SIVbn-PBMC s1 could more efficiently use available CCR5 than SIVmac, a trait we hypothesize arose to circumvent receptor occupation by chemokines. Sequencing analysis showed that all three viruses accumulated different types of mutations, and that more non-synonymous mutations became fixed in SIVbn-PBMC s1 than SIVbn-PBMC s2 and SIVbn-CD4, supporting the notion of stronger fitness pressure in PBMC from different genetic backgrounds. Testing the individual contribution of several newly fixed SIV mutations suggested that is the additive effect of these mutations in SIVbn-PBMC s1 that contributed to its enhanced fitness, as recombinant single mutant viruses showed no difference in replication capacity over the parental SIVmac239 strain. The replicative capacity of SIVbn-PBMC passage 4 (P4) s1 was tested in vivo by infecting baboons intravenously with SIVbn-PBMC P4 s1 or SIVmac251. While animals infected with SIVmac251 showed the known pattern of transient low-level viremia, animals infected with SIVbn-PBMC P4 s1 had undetectable viremia or viral DNA in lymphoid tissue. These studies suggest that adaptation of SIV to grow in baboon primary cells results in mutations that confer increased replicative capacity in the artificial environment of cell culture but make the virus unable to avoid the restrictive factors generated by a complex multicellular organism.
Additional Links: PMID-39006742
PubMed:
Citation:
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@article {pmid39006742,
year = {2024},
author = {Obregon-Perko, V and Mannino, A and Ladner, JT and Hodara, V and Ebrahimi, D and Parodi, L and Callery, J and Palacios, G and Giavedoni, LD},
title = {Adaptation of SIVmac to baboon primary cells results in complete absence of in vivo baboon infectivity.},
journal = {Frontiers in cellular and infection microbiology},
volume = {14},
number = {},
pages = {1408245},
pmid = {39006742},
issn = {2235-2988},
mesh = {Animals ; *Simian Immunodeficiency Virus/genetics/physiology ; *Virus Replication ; *Simian Acquired Immunodeficiency Syndrome/virology/immunology ; *Papio ; Leukocytes, Mononuclear/virology/immunology ; Receptors, CCR5/metabolism/genetics ; CD4-Positive T-Lymphocytes/virology/immunology ; Cells, Cultured ; Serial Passage ; },
abstract = {While simian immunodeficiency virus (SIV) infection is non-pathogenic in naturally infected African nonhuman primate hosts, experimental or accidental infection in rhesus macaques often leads to AIDS. Baboons, widely distributed throughout Africa, do not naturally harbor SIV, and experimental infection of baboons with SIVmac results in transient low-level viral replication. Elucidation of mechanisms of natural immunity in baboons could uncover new targets of antiviral intervention. We tested the hypothesis that an SIVmac adapted to replicate in baboon primary cells will gain the capacity to establish chronic infections in vivo. Here, we generated SIVmac variants in baboon cells through serial passage in PBMC from different donors (SIVbn-PBMC s1), in PBMC from the same donors (SIVbn-PBMC s2), or in isolated CD4 cells from the same donors used for series 2 (SIVbn-CD4). While SIVbn-PBMC s1 and SIVbn-CD4 demonstrated increased replication capacity, SIVbn-PBMC s2 did not. Pharmacological blockade of CCR5 revealed SIVbn-PBMC s1 could more efficiently use available CCR5 than SIVmac, a trait we hypothesize arose to circumvent receptor occupation by chemokines. Sequencing analysis showed that all three viruses accumulated different types of mutations, and that more non-synonymous mutations became fixed in SIVbn-PBMC s1 than SIVbn-PBMC s2 and SIVbn-CD4, supporting the notion of stronger fitness pressure in PBMC from different genetic backgrounds. Testing the individual contribution of several newly fixed SIV mutations suggested that is the additive effect of these mutations in SIVbn-PBMC s1 that contributed to its enhanced fitness, as recombinant single mutant viruses showed no difference in replication capacity over the parental SIVmac239 strain. The replicative capacity of SIVbn-PBMC passage 4 (P4) s1 was tested in vivo by infecting baboons intravenously with SIVbn-PBMC P4 s1 or SIVmac251. While animals infected with SIVmac251 showed the known pattern of transient low-level viremia, animals infected with SIVbn-PBMC P4 s1 had undetectable viremia or viral DNA in lymphoid tissue. These studies suggest that adaptation of SIV to grow in baboon primary cells results in mutations that confer increased replicative capacity in the artificial environment of cell culture but make the virus unable to avoid the restrictive factors generated by a complex multicellular organism.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Simian Immunodeficiency Virus/genetics/physiology
*Virus Replication
*Simian Acquired Immunodeficiency Syndrome/virology/immunology
*Papio
Leukocytes, Mononuclear/virology/immunology
Receptors, CCR5/metabolism/genetics
CD4-Positive T-Lymphocytes/virology/immunology
Cells, Cultured
Serial Passage
RevDate: 2024-09-18
CmpDate: 2024-09-12
Molecular mechanism of TRIM32 in antiviral immunity in rainbow trout (Oncorhynchus mykiss).
Fish & shellfish immunology, 153:109765.
TRIM family proteins are widely found in multicellular organisms and are involved in a wide range of life activities, and also act as crucial regulators in the antiviral natural immune response. This study aimed to reveal the molecular mechanism of rainbow trout TRIM protein in the anti-IHNV process. The results demonstrated that 99.1 % homology between the rainbow trout and the chinook salmon (Oncorhynchus tshawytscha) TRIM32. When rainbow trout were infected with IHNV, the TRIM32 was highly expressed in the gill, spleen, kidney and blood. Meanwhile, rainbow trout TRIM32 has E3 ubiquitin ligase activity and undergoes K29-linked polyubiquitination modifications dependent on the RING structural domain was determined by immunoprecipitation. TRIM32 could interact with the NV protein of IHNV and degrade NV protein through the ubiquitin-proteasome pathway, and was also able to activate NF-κB transcription, thereby inhibiting the replication of IHNV. Moreover, the results of the animal studies showed that the survival rate of rainbow trout overexpressing TRIM32 was 70.2 % which was significantly higher than that of the control group, and stimulating the body to produce high levels of IgM when the host was infected with the virus. In addition, TRIM32 can activate the NF-κB signalling pathway and participate in the antiviral natural immune response. The results of this study will help us to understand the molecular mechanism of TRIM protein resistance in rainbow trout, and provide new ideas for disease resistance breeding, vaccine development and immune formulation development in rainbow trout.
Additional Links: PMID-39004296
Publisher:
PubMed:
Citation:
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@article {pmid39004296,
year = {2024},
author = {Zhang, M and Sun, J and Zhang, F and Zhang, Y and Wu, M and Kong, W and Guan, X and Liu, M},
title = {Molecular mechanism of TRIM32 in antiviral immunity in rainbow trout (Oncorhynchus mykiss).},
journal = {Fish & shellfish immunology},
volume = {153},
number = {},
pages = {109765},
doi = {10.1016/j.fsi.2024.109765},
pmid = {39004296},
issn = {1095-9947},
mesh = {Animals ; *Oncorhynchus mykiss/immunology ; *Fish Diseases/immunology ; *Fish Proteins/genetics/immunology ; *Rhabdoviridae Infections/immunology/veterinary ; *Immunity, Innate/genetics ; *Tripartite Motif Proteins/genetics/immunology ; Ubiquitin-Protein Ligases/genetics/immunology ; Gene Expression Regulation/immunology ; Gene Expression Profiling/veterinary ; Infectious hematopoietic necrosis virus/immunology/physiology ; Sequence Alignment/veterinary ; Phylogeny ; },
abstract = {TRIM family proteins are widely found in multicellular organisms and are involved in a wide range of life activities, and also act as crucial regulators in the antiviral natural immune response. This study aimed to reveal the molecular mechanism of rainbow trout TRIM protein in the anti-IHNV process. The results demonstrated that 99.1 % homology between the rainbow trout and the chinook salmon (Oncorhynchus tshawytscha) TRIM32. When rainbow trout were infected with IHNV, the TRIM32 was highly expressed in the gill, spleen, kidney and blood. Meanwhile, rainbow trout TRIM32 has E3 ubiquitin ligase activity and undergoes K29-linked polyubiquitination modifications dependent on the RING structural domain was determined by immunoprecipitation. TRIM32 could interact with the NV protein of IHNV and degrade NV protein through the ubiquitin-proteasome pathway, and was also able to activate NF-κB transcription, thereby inhibiting the replication of IHNV. Moreover, the results of the animal studies showed that the survival rate of rainbow trout overexpressing TRIM32 was 70.2 % which was significantly higher than that of the control group, and stimulating the body to produce high levels of IgM when the host was infected with the virus. In addition, TRIM32 can activate the NF-κB signalling pathway and participate in the antiviral natural immune response. The results of this study will help us to understand the molecular mechanism of TRIM protein resistance in rainbow trout, and provide new ideas for disease resistance breeding, vaccine development and immune formulation development in rainbow trout.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Oncorhynchus mykiss/immunology
*Fish Diseases/immunology
*Fish Proteins/genetics/immunology
*Rhabdoviridae Infections/immunology/veterinary
*Immunity, Innate/genetics
*Tripartite Motif Proteins/genetics/immunology
Ubiquitin-Protein Ligases/genetics/immunology
Gene Expression Regulation/immunology
Gene Expression Profiling/veterinary
Infectious hematopoietic necrosis virus/immunology/physiology
Sequence Alignment/veterinary
Phylogeny
RevDate: 2024-07-12
CmpDate: 2024-07-11
Natural selection drives emergent genetic homogeneity in a century-scale experiment with barley.
Science (New York, N.Y.), 385(6705):eadl0038.
Direct observation is central to our understanding of adaptation, but evolution is rarely documented in a large, multicellular organism for more than a few generations. In this study, we observed evolution across a century-scale competition experiment, barley composite cross II (CCII). CCII was founded in 1929 in Davis, California, with thousands of genotypes, but we found that natural selection has massively reduced genetic diversity, leading to a single lineage constituting most of the population by generation 50. Selection favored alleles originating from climates similar to that of Davis and targeted loci contributing to reproductive development, including the barley diversification loci Vrs1, HvCEN, Ppd-H1, and Vrn-H2. Our findings point to selection as the predominant force shaping genomic variation in one of the world's oldest biological experiments.
Additional Links: PMID-38991084
Publisher:
PubMed:
Citation:
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@article {pmid38991084,
year = {2024},
author = {Landis, JB and Guercio, AM and Brown, KE and Fiscus, CJ and Morrell, PL and Koenig, D},
title = {Natural selection drives emergent genetic homogeneity in a century-scale experiment with barley.},
journal = {Science (New York, N.Y.)},
volume = {385},
number = {6705},
pages = {eadl0038},
doi = {10.1126/science.adl0038},
pmid = {38991084},
issn = {1095-9203},
mesh = {*Hordeum/genetics ; *Selection, Genetic ; *Genetic Variation ; *Alleles ; Genotype ; Crosses, Genetic ; Genome, Plant ; },
abstract = {Direct observation is central to our understanding of adaptation, but evolution is rarely documented in a large, multicellular organism for more than a few generations. In this study, we observed evolution across a century-scale competition experiment, barley composite cross II (CCII). CCII was founded in 1929 in Davis, California, with thousands of genotypes, but we found that natural selection has massively reduced genetic diversity, leading to a single lineage constituting most of the population by generation 50. Selection favored alleles originating from climates similar to that of Davis and targeted loci contributing to reproductive development, including the barley diversification loci Vrs1, HvCEN, Ppd-H1, and Vrn-H2. Our findings point to selection as the predominant force shaping genomic variation in one of the world's oldest biological experiments.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Hordeum/genetics
*Selection, Genetic
*Genetic Variation
*Alleles
Genotype
Crosses, Genetic
Genome, Plant
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ESP Quick Facts
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In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.
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In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.
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In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.
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