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Bibliography on: Origin of Multicellular Eukaryotes

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ESP: PubMed Auto Bibliography 26 Dec 2024 at 01:49 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®)

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RevDate: 2024-12-23

Doctrove Q, Park Y, Calame DG, et al (2024)

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.

RevDate: 2024-12-23
CmpDate: 2024-12-23

Laisné M, Lupien M, C Vallot (2025)

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.

RevDate: 2024-12-21
CmpDate: 2024-12-21

Ustyantsev IG, Borodulina OR, DA Kramerov (2024)

[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.

RevDate: 2024-12-21
CmpDate: 2024-12-21

Symonds K, Wali U, Duff L, et al (2024)

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.

RevDate: 2024-12-20
CmpDate: 2024-12-20

Nguyen NM, E Farge (2024)

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.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Smith ML, Marting PR, Bailey CS, et al (2024)

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.

RevDate: 2024-12-14
CmpDate: 2024-12-14

Krueger KE (2024)

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.

RevDate: 2024-12-13
CmpDate: 2024-12-13

Sun Y, Chen Z, Jin M, et al (2024)

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.

RevDate: 2024-12-09

Bourrat P, Takacs P, Doulcier G, et al (2024)

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.

RevDate: 2024-12-06

Torruella G, Galindo LJ, Moreira D, et al (2024)

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.

RevDate: 2024-12-04
CmpDate: 2024-12-04

Wen T, KH Cheong (2024)

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.

RevDate: 2024-12-04

Durairaj P, S Li (2022)

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.

RevDate: 2024-12-01
CmpDate: 2024-12-01

Wu J, Gupta G, Buerki-Thurnherr T, et al (2024)

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.

RevDate: 2024-12-01
CmpDate: 2024-12-01

Dvořáček J, D Kodrík (2024)

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.

RevDate: 2024-11-29
CmpDate: 2024-11-30

He R, Liu Y, Fu W, et al (2024)

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.

RevDate: 2024-11-28
CmpDate: 2024-11-28

Denoeud F, Godfroy O, Cruaud C, et al (2024)

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.

RevDate: 2024-11-28

Yang R, Hunker O, Wise M, et al (2024)

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.

RevDate: 2024-11-28
CmpDate: 2024-11-28

Kosztyo BS, EJ Richards (2024)

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.

RevDate: 2024-11-27
CmpDate: 2024-11-27

Madhani H, A Nejad Kourki (2024)

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.

RevDate: 2024-11-27
CmpDate: 2024-11-27

Stein WD (2024)

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.

RevDate: 2024-11-27
CmpDate: 2024-11-27

Dahlin P, AC Ruthes (2024)

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.

RevDate: 2024-11-25
CmpDate: 2024-11-25

Sheikh S, Fu CJ, Brown MW, et al (2024)

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.

RevDate: 2024-11-25
CmpDate: 2024-11-25

Aravind L, Nicastro GG, Iyer LM, et al (2024)

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.

RevDate: 2024-11-21
CmpDate: 2024-11-21

Petersen M, Reyes-Vigil F, Campo M, et al (2024)

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.

RevDate: 2024-11-19
CmpDate: 2024-11-19

Dierschke T, Levins J, Lampugnani ER, et al (2024)

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.

RevDate: 2024-11-16
CmpDate: 2024-11-15

Gao Y, Tan DS, Girbig M, et al (2024)

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.

RevDate: 2024-11-13
CmpDate: 2024-11-13

Huang J, Larmore CJ, Priest SJ, et al (2024)

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.

RevDate: 2024-11-07
CmpDate: 2024-11-07

Lynch M (2024)

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.

RevDate: 2024-11-13
CmpDate: 2024-11-13

Olivetta M, Bhickta C, Chiaruttini N, et al (2024)

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.

RevDate: 2024-11-09
CmpDate: 2024-11-07

Uppal S, Waterworth SC, Nick A, et al (2024)

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.

RevDate: 2024-11-08
CmpDate: 2024-11-08

Evans SD, Hughes IV, Hughes EB, et al (2024)

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.

RevDate: 2024-11-07
CmpDate: 2024-11-07

Neumann SA, Gaspin C, J Sáez-Vásquez (2024)

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.

RevDate: 2024-11-04
CmpDate: 2024-11-04

Yao M, Su Y, Xiong R, et al (2024)

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.

RevDate: 2024-10-31
CmpDate: 2024-10-31

Petit C, Kojak E, Webster S, et al (2024)

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.

RevDate: 2024-10-30
CmpDate: 2024-10-30

Usmanova DR, Plata G, D Vitkup (2024)

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.

RevDate: 2024-10-29
CmpDate: 2024-10-29

Wolnik J, Adamska P, Oleksy A, et al (2024)

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.

RevDate: 2024-10-28
CmpDate: 2024-10-28

Erard M, Favard C, Lavis LD, et al (2024)

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).

RevDate: 2024-10-24

Lee SH, Dubey N, J Jeon (2024)

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.

RevDate: 2024-10-24

Lotharukpong JS, Zheng M, Luthringer R, et al (2024)

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.

RevDate: 2024-10-10

Mazéas L, Bouguerba-Collin A, Cock JM, et al (2024)

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.

RevDate: 2024-10-09
CmpDate: 2024-10-09

Staps M, Tarnita CE, M Kawakatsu (2024)

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.

RevDate: 2024-10-09
CmpDate: 2024-10-09

Karin O (2024)

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.

RevDate: 2024-10-08
CmpDate: 2024-10-08

Bell-Roberts L, Turner JFR, Werner GDA, et al (2024)

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.

RevDate: 2024-10-08

Laporte D, I Sagot (2024)

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.

RevDate: 2024-10-08
CmpDate: 2024-10-08

Babonis LS (2024)

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.

RevDate: 2024-10-07
CmpDate: 2024-10-07

Liao H, Choi J, J Shendure (2024)

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.

RevDate: 2024-10-07
CmpDate: 2024-10-07

Ros-Rocher N (2024)

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.

RevDate: 2024-10-03
CmpDate: 2024-09-20

Zhang H, Wang X, Qu M, et al (2024)

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.

RevDate: 2024-09-21
CmpDate: 2024-09-14

Ueki N, KI Wakabayashi (2024)

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.

RevDate: 2024-09-16
CmpDate: 2024-09-14

Kasperski A, HH Heng (2024)

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.

RevDate: 2024-09-13
CmpDate: 2024-09-13

Mo J, Bae J, Saqib J, et al (2024)

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.

RevDate: 2024-09-20
CmpDate: 2024-09-20

Appleton E, Mehdipour N, Daifuku T, et al (2024)

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.

RevDate: 2024-08-25
CmpDate: 2024-08-23

Li XC, Srinivasan V, Laiker I, et al (2024)

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.

RevDate: 2024-07-27
CmpDate: 2024-07-28

Yousefi Taemeh S, Dehdilani N, Goshayeshi L, et al (2024)

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.

RevDate: 2024-10-02
CmpDate: 2024-10-02

Hehmeyer J, Plessier F, H Marlow (2024)

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.

RevDate: 2024-07-16
CmpDate: 2024-07-15

Obregon-Perko V, Mannino A, Ladner JT, et al (2024)

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.

RevDate: 2024-09-18
CmpDate: 2024-09-12

Zhang M, Sun J, Zhang F, et al (2024)

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.

RevDate: 2024-07-12
CmpDate: 2024-07-11

Landis JB, Guercio AM, Brown KE, et al (2024)

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.

RevDate: 2024-07-09
CmpDate: 2024-07-09

Kulakova MA, Maslakov GP, LO Poliushkevich (2024)

Irreducible Complexity of Hox Gene: Path to the Canonical Function of the Hox Cluster.

Biochemistry. Biokhimiia, 89(6):987-1001.

The evolution of major taxa is often associated with the emergence of new gene families. In all multicellular animals except sponges and comb jellies, the genomes contain Hox genes, which are crucial regulators of development. The canonical function of Hox genes involves colinear patterning of body parts in bilateral animals. This general function is implemented through complex, precisely coordinated mechanisms, not all of which are evolutionarily conserved and fully understood. We suggest that the emergence of this regulatory complexity was preceded by a stage of cooperation between more ancient morphogenetic programs or their individual elements. Footprints of these programs may be present in modern animals to execute non-canonical Hox functions. Non-canonical functions of Hox genes are involved in maintaining terminal nerve cell specificity, autophagy, oogenesis, pre-gastrulation embryogenesis, vertical signaling, and a number of general biological processes. These functions are realized by the basic properties of homeodomain protein and could have triggered the evolution of ParaHoxozoa and Nephrozoa subsequently. Some of these non-canonical Hox functions are discussed in our review.

RevDate: 2024-07-09
CmpDate: 2024-07-06

Wang P, Driscoll WW, M Travisano (2024)

Genomic sequencing reveals convergent adaptation during experimental evolution in two budding yeast species.

Communications biology, 7(1):825.

Convergent evolution is central in the origins of multicellularity. Identifying the basis for convergent multicellular evolution is challenging because of the diverse evolutionary origins and environments involved. Haploid Kluyveromyces lactis populations evolve multicellularity during selection for increased settling in liquid media. Strong genomic and phenotypic convergence is observed between K. lactis and previously selected S. cerevisiae populations under similar selection, despite their >100-million-year divergence. We find K. lactis multicellularity is conferred by mutations in genes ACE2 or AIM44, with ACE2 being predominant. They are a subset of the six genes involved in the S. cerevisiae multicellularity. Both ACE2 and AIM44 regulate cell division, indicating that the genetic convergence is likely due to conserved cellular replication mechanisms. Complex population dynamics involving multiple ACE2/AIM44 genotypes are found in most K. lactis lineages. The results show common ancestry and natural selection shape convergence while chance and contingency determine the degree of divergence.

RevDate: 2024-08-19
CmpDate: 2024-07-20

Bhattacharya R, Brown JS, Gatenby RA, et al (2024)

A gene for all seasons: The evolutionary consequences of HIF-1 in carcinogenesis, tumor growth and metastasis.

Seminars in cancer biology, 102-103:17-24.

Oxygen played a pivotal role in the evolution of multicellularity during the Cambrian Explosion. Not surprisingly, responses to fluctuating oxygen concentrations are integral to the evolution of cancer-a disease characterized by the breakdown of multicellularity. Poorly organized tumor vasculature results in chaotic patterns of blood flow characterized by large spatial and temporal variations in intra-tumoral oxygen concentrations. Hypoxia-inducible growth factor (HIF-1) plays a pivotal role in enabling cells to adapt, metabolize, and proliferate in low oxygen conditions. HIF-1 is often constitutively activated in cancers, underscoring its importance in cancer progression. Here, we argue that the phenotypic changes mediated by HIF-1, in addition to adapting the cancer cells to their local environment, also "pre-adapt" them for proliferation at distant, metastatic sites. HIF-1-mediated adaptations include a metabolic shift towards anaerobic respiration or glycolysis, activation of cell survival mechanisms like phenotypic plasticity and epigenetic reprogramming, and formation of tumor vasculature through angiogenesis. Hypoxia induced epigenetic reprogramming can trigger epithelial to mesenchymal transition in cancer cells-the first step in the metastatic cascade. Highly glycolytic cells facilitate local invasion by acidifying the tumor microenvironment. New blood vessels, formed due to angiogenesis, provide cancer cells a conduit to the circulatory system. Moreover, survival mechanisms acquired by cancer cells in the primary site allow them to remodel tissue at the metastatic site generating tumor promoting microenvironment. Thus, hypoxia in the primary tumor promoted adaptations conducive to all stages of the metastatic cascade from the initial escape entry into a blood vessel, intravascular survival, extravasation into distant tissues, and establishment of secondary tumors.

RevDate: 2024-09-05
CmpDate: 2024-09-03

Ghosh S, Mellado Sanchez M, Sue-Ob K, et al (2024)

Charting the evolutionary path of the SUMO modification system in plants reveals molecular hardwiring of development to stress adaptation.

The Plant cell, 36(9):3131-3144.

SUMO modification is part of the spectrum of Ubiquitin-like (UBL) systems that give rise to proteoform complexity through post-translational modifications (PTMs). Proteoforms are essential modifiers of cell signaling for plant adaptation to changing environments. Exploration of the evolutionary emergence of Ubiquitin-like (UBL) systems unveils their origin from prokaryotes, where it is linked to the mechanisms that enable sulfur uptake into biomolecules. We explore the emergence of the SUMO machinery across the plant lineage from single-cell to land plants. We reveal the evolutionary point at which plants acquired the ability to form SUMO chains through the emergence of SUMO E4 ligases, hinting at its role in facilitating multicellularity. Additionally, we explore the possible mechanism for the neofunctionalization of SUMO proteases through the fusion of conserved catalytic domains with divergent sequences. We highlight the pivotal role of SUMO proteases in plant development and adaptation, offering new insights into target specificity mechanisms of SUMO modification during plant evolution. Correlating the emergence of adaptive traits in the plant lineage with established experimental evidence for SUMO in developmental processes, we propose that SUMO modification has evolved to link developmental processes to adaptive functions in land plants.

RevDate: 2024-08-12
CmpDate: 2024-08-12

Mascarenhas DP, DS Zamboni (2024)

Innate immune responses and monocyte-derived phagocyte recruitment in protective immunity to pathogenic bacteria: insights from Legionella pneumophila.

Current opinion in microbiology, 80:102495.

Legionella species are Gram-negative intracellular bacteria that evolved in soil and freshwater environments, where they infect and replicate within various unicellular protozoa. The primary virulence factor of Legionella is the expression of a type IV secretion system (T4SS), which contributes to the translocation of effector proteins that subvert biological processes of the host cells. Because of its evolution in unicellular organisms, T4SS effector proteins are not adapted to subvert specific mammalian signaling pathways and immunity. Consequently, Legionella pneumophila has emerged as an interesting infection model for investigating immune responses against pathogenic bacteria in multicellular organisms. This review highlights recent advances in our understanding of mammalian innate immunity derived from studies involving L. pneumophila. This includes recent insights into inflammasome-mediated mechanisms restricting bacterial replication in macrophages, mechanisms inducing cell death in response to infection, induction of effector-triggered immunity, activation of specific pulmonary cell types in mammalian lungs, and the protective role of recruiting monocyte-derived cells to infected lungs.

RevDate: 2024-09-11
CmpDate: 2024-09-11

Ajay A, Begum T, Arya A, et al (2024)

Global and local genomic features together modulate the spontaneous single nucleotide mutation rate.

Computational biology and chemistry, 112:108107.

Spontaneous mutations are evolutionary engines as they generate variants for the evolutionary downstream processes that give rise to speciation and adaptation. Single nucleotide mutations (SNM) are the most abundant type of mutations among them. Here, we perform a meta-analysis to quantify the influence of selected global genomic parameters (genome size, genomic GC content, genomic repeat fraction, number of coding genes, gene count, and strand bias in prokaryotes) and local genomic features (local GC content, repeat content, CpG content and the number of SNM at CpG islands) on spontaneous SNM rates across the tree of life (prokaryotes, unicellular eukaryotes, multicellular eukaryotes) using wild-type sequence data in two different taxon classification systems. We find that the spontaneous SNM rates in our data are correlated with many genomic features in prokaryotes and unicellular eukaryotes irrespective of their sample sizes. On the other hand, only the number of coding genes was correlated with the spontaneous SNM rates in multicellular eukaryotes primarily contributed by vertebrates data. Considering local features, we notice that local GC content and CpG content significantly were correlated with the spontaneous SNM rates in the unicellular eukaryotes, while local repeat fraction is an important feature in prokaryotes and certain specific uni- and multi-cellular eukaryotes. Such predictive features of the spontaneous SNM rates often support non-linear models as the best fit compared to the linear model. We also observe that the strand asymmetry in prokaryotes plays an important role in determining the spontaneous SNM rates but the SNM spectrum does not.

RevDate: 2024-07-19
CmpDate: 2024-06-07

Patel AS, I Yanai (2024)

A developmental constraint model of cancer cell states and tumor heterogeneity.

Cell, 187(12):2907-2918.

Cancer is a disease that stems from a fundamental liability inherent to multicellular life forms in which an individual cell is capable of reneging on the interests of the collective organism. Although cancer is commonly described as an evolutionary process, a less appreciated aspect of tumorigenesis may be the constraints imposed by the organism's developmental programs. Recent work from single-cell transcriptomic analyses across a range of cancer types has revealed the recurrence, plasticity, and co-option of distinct cellular states among cancer cell populations. Here, we note that across diverse cancer types, the observed cell states are proximate within the developmental hierarchy of the cell of origin. We thus posit a model by which cancer cell states are directly constrained by the organism's "developmental map." According to this model, a population of cancer cells traverses the developmental map, thereby generating a heterogeneous set of states whose interactions underpin emergent tumor behavior.

RevDate: 2024-08-03
CmpDate: 2024-07-23

Errbii M, Gadau J, Becker K, et al (2024)

Causes and consequences of a complex recombinational landscape in the ant Cardiocondyla obscurior.

Genome research, 34(6):863-876.

Eusocial Hymenoptera have the highest recombination rates among all multicellular animals studied so far, but it is unclear why this is and how this affects the biology of individual species. A high-resolution linkage map for the ant Cardiocondyla obscurior corroborates genome-wide high recombination rates reported for ants (8.1 cM/Mb). However, recombination is locally suppressed in regions that are enriched with TEs, that have strong haplotype divergence, or that show signatures of epistatic selection in C. obscurior The results do not support the hypotheses that high recombination rates are linked to phenotypic plasticity or to modulating selection efficiency. Instead, genetic diversity and the frequency of structural variants correlate positively with local recombination rates, potentially compensating for the low levels of genetic variation expected in haplodiploid social Hymenoptera with low effective population size. Ultimately, the data show that recombination contributes to within-population polymorphism and to the divergence of the lineages within C. obscurior.

RevDate: 2024-08-25
CmpDate: 2024-08-23

Bierenbroodspot MJ, Pröschold T, Fürst-Jansen JMR, et al (2024)

Phylogeny and evolution of streptophyte algae.

Annals of botany, 134(3):385-400.

The Streptophyta emerged about a billion years ago. Nowadays, this branch of the green lineage is most famous for one of its clades, the land plants (Embryophyta). Although Embryophyta make up the major share of species numbers in Streptophyta, there is a diversity of probably >5000 species of streptophyte algae that form a paraphyletic grade next to land plants. Here, we focus on the deep divergences that gave rise to the diversity of streptophytes, hence particularly on the streptophyte algae. Phylogenomic efforts have not only clarified the position of streptophyte algae relative to land plants, but recent efforts have also begun to unravel the relationships and major radiations within streptophyte algal diversity. We illustrate how new phylogenomic perspectives have changed our view on the evolutionary emergence of key traits, such as intricate signalling networks that are intertwined with multicellular growth and the chemodiverse hotbed from which they emerged. These traits are key for the biology of land plants but were bequeathed from their algal progenitors.

RevDate: 2024-06-03
CmpDate: 2024-05-31

Stillinovic M, Sarangdhar MA, Andina N, et al (2024)

Ribonuclease inhibitor and angiogenin system regulates cell type-specific global translation.

Science advances, 10(22):eadl0320.

Translation of mRNAs is a fundamental process that occurs in all cell types of multicellular organisms. Conventionally, it has been considered a default step in gene expression, lacking specific regulation. However, recent studies have documented that certain mRNAs exhibit cell type-specific translation. Despite this, it remains unclear whether global translation is controlled in a cell type-specific manner. By using human cell lines and mouse models, we found that deletion of the ribosome-associated protein ribonuclease inhibitor 1 (RNH1) decreases global translation selectively in hematopoietic-origin cells but not in the non-hematopoietic-origin cells. RNH1-mediated cell type-specific translation is mechanistically linked to angiogenin-induced ribosomal biogenesis. Collectively, this study unravels the existence of cell type-specific global translation regulators and highlights the complex translation regulation in vertebrates.

RevDate: 2024-06-01
CmpDate: 2024-05-29

Li XC, Gandara L, Ekelöf M, et al (2024)

Rapid response of fly populations to gene dosage across development and generations.

Nature communications, 15(1):4551.

Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges remains limited. Here, we have examined the phenotypic consequences of disturbing the bicoid regulatory network in early Drosophila embryos. We generated flies with two extra copies of bicoid, which causes a posterior shift of the network's regulatory outputs and a decrease in fitness. We subjected these flies to EMS mutagenesis, followed by experimental evolution. After only 8-15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level.

RevDate: 2024-09-02
CmpDate: 2024-07-02

Cho CJ, Brown JW, JC Mills (2024)

Origins of cancer: ain't it just mature cells misbehaving?.

The EMBO journal, 43(13):2530-2551.

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain the capacity to return to the cell cycle and required the tumor suppressor p53. Finally, we examine an example of an evolutionarily conserved program for the plasticity of differentiated cells, paligenosis, which helps explain the origins of cancers that arise in adults. Altogether, we highlight new perspectives for understanding the development of cancer and new strategies for preventing carcinogenic cellular transformations from occurring.

RevDate: 2024-05-24
CmpDate: 2024-05-21

MacDonald N, Raven N, Diep W, et al (2024)

The molecular evolution of cancer associated genes in mammals.

Scientific reports, 14(1):11650.

Cancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected. Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes. Therefore, we investigated the evolutionary history of cancer associated gene sequences across 384 mammalian taxa, to detect signatures of selection across categories of oncogenes (GRB2, FGL2 and CDC42), tumour suppressors (LITAF, Casp8 and BRCA2) and immune genes (IL2, CD274 and B2M). This approach allowed us to conduct a fine scale analysis of gene wide and site-specific signatures of selection across mammalian lineages under the lens of cancer susceptibility. Phylogenetic analyses revealed that for most species the evolution of cancer associated genes follows the species' evolution. The gene wide selection analyses revealed oncogenes being the most conserved, tumour suppressor and immune genes having similar amounts of episodic diversifying selection. Despite BRCA2's status as a key caretaker gene, episodic diversifying selection was detected across mammals. The site-specific selection analyses revealed that the two apoptosis associated domains of the Casp8 gene of bats (Chiroptera) are under opposing forces of selection (positive and negative respectively), highlighting the importance of site-specific selection analyses to understand the evolution of highly complex gene families. Our results highlighted the need to critically assess different types of selection pressure on cancer associated genes when investigating evolutionary adaptations to cancer across the tree of life. This study provides an extensive assessment of cancer associated genes in mammals with highly representative, and substantially large sample size for a comparative genomic analysis in the field and identifies various avenues for future research into the mechanisms of cancer resistance and susceptibility in mammals.

RevDate: 2024-09-10
CmpDate: 2024-05-21

Lenz G (2024)

Heterogeneity generating capacity in tumorigenesis and cancer therapeutics.

Biochimica et biophysica acta. Molecular basis of disease, 1870(5):167226.

Cells of multicellular organisms generate heterogeneity in a controlled and transient fashion during embryogenesis, which can be reactivated in pathologies such as cancer. Although genomic heterogeneity is an important part of tumorigenesis, continuous generation of phenotypic heterogeneity is central for the adaptation of cancer cells to the challenges of tumorigenesis and response to therapy. Here I discuss the capacity of generating heterogeneity, hereafter called cell hetness, in cancer cells both as the activation of hetness oncogenes and inactivation of hetness tumor suppressor genes, which increase the generation of heterogeneity, ultimately producing an increase in adaptability and cell fitness. Transcriptomic high hetness states in therapy-tolerant cell states denote its importance in cancer resistance to therapy. The definition of the concept of hetness will allow the understanding of its origins, its control during embryogenesis, its loss of control in tumorigenesis and cancer therapeutics and its active targeting.

RevDate: 2024-05-19
CmpDate: 2024-05-17

Oszoli I, I Zachar (2024)

Group-selection via aggregative propagule-formation enables cooperative multicellularity in an individual based, spatial model.

PLoS computational biology, 20(5):e1012107.

The emergence of multicellularity is one of the major transitions in evolution that happened multiple times independently. During aggregative multicellularity, genetically potentially unrelated lineages cooperate to form transient multicellular groups. Unlike clonal multicellularity, aggregative multicellular organisms do not rely on kin selection instead other mechanisms maintain cooperation against cheater phenotypes that benefit from cooperators but do not contribute to groups. Spatiality with limited diffusion can facilitate group selection, as interactions among individuals are restricted to local neighbourhoods only. Selection for larger size (e.g. avoiding predation) may facilitate the emergence of aggregation, though it is unknown, whether and how much role such selection played during the evolution of aggregative multicellularity. We have investigated the effect of spatiality and the necessity of predation on the stability of aggregative multicellularity via individual-based modelling on the ecological timescale. We have examined whether aggregation facilitates the survival of cooperators in a temporally heterogeneous environment against cheaters, where only a subset of the population is allowed to periodically colonize a new, resource-rich habitat. Cooperators constitutively produce adhesive molecules to promote aggregation and propagule-formation while cheaters spare this expense to grow faster but cannot aggregate on their own, hence depending on cooperators for long-term survival. We have compared different population-level reproduction modes with and without individual selection (predation) to evaluate the different hypotheses. In a temporally homogeneous environment without propagule-based colonization, cheaters always win. Predation can benefit cooperators, but it is not enough to maintain the necessary cooperator amount in successive dispersals, either randomly or by fragmentation. Aggregation-based propagation however can ensure the adequate ratio of cooperators-to-cheaters in the propagule and is sufficient to do so even without predation. Spatiality combined with temporal heterogeneity helps cooperators via group selection, thus facilitating aggregative multicellularity. External stress selecting for larger size (e.g. predation) may facilitate aggregation, however, according to our results, it is neither necessary nor sufficient for aggregative multicellularity to be maintained when there is effective group-selection.

RevDate: 2024-06-13
CmpDate: 2024-06-05

Pozdnyakov IR, Selyuk AO, Kalashnikova VA, et al (2024)

HMG-B transcription factors of unicellular opisthokonts and their relatedness to the Sox-Tcf/Lef-Mata proteins of Metazoa and fungi.

Gene, 921:148520.

A phylogenetic analysis of transcription factors of the Sox-Tcf/Lef-Mata (STM) family of the HMG-B superfamily was carried out in order to clarify the evolutionary roots of the Wnt signaling pathway in unicellular organisms. The data set for analysis included protein sequences of metazoans, fungi, unicellular opisthokonts, apusomonads and amoebozoans. The topology of the phylogenetic tree suggests that STM-related proteins arose in the common ancestor of Opisthokonta and Amoebozoa, two of amoebozoan STM proteins are sister-related to opisthokont ones and the three known lineages of STM transcription factors (STM family in narrow sence) are found in Opisthokonta only. Of these, the holozoan Sox protein branch is the result of either the first or second branching, that originated in the common ancestor of Opisthokonta. The lineage containing Tcf/Lef proteins (holozoan) and the lineage containing Mata proteins (holomycotan) are sister. They derived either at the time of the Holozoa and Holomycota divergence or originate from two paralogs of the common ancestor of Opisthokonta, which arose after the separation of the Sox lineage. Interaction with Armadillo-like proteins may be an original feature of the STM protein family and existed in the unicellular ancestors of multicellular animals; a connection is possible between the presence of Mata-related proteins in Aphelidium protococcorum and specific genome feature of this species.

RevDate: 2024-10-02
CmpDate: 2024-05-15

Feng X, Zheng J, Irisarri I, et al (2024)

Genomes of multicellular algal sisters to land plants illuminate signaling network evolution.

Nature genetics, 56(5):1018-1031.

Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum. We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

RevDate: 2024-07-02
CmpDate: 2024-04-30

Trigos AS, Bongiovanni F, Zhang Y, et al (2024)

Disruption of metazoan gene regulatory networks in cancer alters the balance of co-expression between genes of unicellular and multicellular origins.

Genome biology, 25(1):110.

BACKGROUND: Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism, and protein translation. Multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) that arose during metazoan evolution are frequently altered in cancer, resulting in over-expression of unicellular genes. We propose that an imbalance in co-expression of unicellular (UC) and multicellular (MC) genes is a driving force in cancer.

RESULTS: We combine gene co-expression analysis to infer changes to GRNs in cancer with protein sequence conservation data to distinguish genes with UC and MC origins. Co-expression networks created using RNA sequencing data from 31 tumor types and normal tissue samples are divided into modules enriched for UC genes, MC genes, or mixed UC-MC modules. The greatest differences between tumor and normal tissue co-expression networks occur within mixed UC-MC modules. MC and UC genes not commonly co-expressed in normal tissues form distinct co-expression modules seen only in tumors. The degree of rewiring of genes within mixed UC-MC modules increases with tumor grade and stage. Mixed UC-MC modules are enriched for somatic mutations in cancer genes, particularly amplifications, suggesting an important driver of the rewiring observed in tumors is copy number changes.

CONCLUSIONS: Our study shows the greatest changes to gene co-expression patterns during tumor progression occur between genes of MC and UC origins, implicating the breakdown and rewiring of metazoan gene regulatory networks in cancer development and progression.

RevDate: 2024-06-11
CmpDate: 2024-06-11

Tsuchikane Y, Watanabe M, Kawaguchi YW, et al (2024)

Diversity of genome size and chromosome number in homothallic and heterothallic strains of the Closterium peracerosum-strigosum-littorale complex (Desmidiales, Zygnematophyceae, Streptophyta).

Journal of phycology, 60(3):654-667.

The evolutionary transitions of mating systems between outcrossing and self-fertilization are often suggested to associate with the cytological and genomic changes, but the empirical reports are limited in multicellular organisms. Here we used the unicellular zygnematophycean algae, the Closterium peracerosum-strigosum-littorale (C. psl.) complex, to address whether genomic properties such as genome sizes and chromosome numbers are associated with mating system transitions between homothallism (self-fertility) and heterothallism (self-sterility). Phylogenetic analysis revealed the polyphyly of homothallic strains, suggesting multiple transitions between homothallism and heterothallism in the C. psl. complex. Flow cytometry analysis identified a more than 2-fold genome size variation, ranging from 0.53 to 1.42 Gbp, which was positively correlated with chromosome number variation between strains. Although we did not find consistent trends in genome size change and mating system transitions, the mean chromosome sizes tend to be smaller in homothallic strains than in their relative heterothallic strains. This result suggests that homothallic strains possibly have more fragmented chromosomes, which is consistent with the argument that self-fertilizing populations may tolerate more chromosomal rearrangements.

RevDate: 2024-06-13
CmpDate: 2024-06-13

Wu T, Huang J, Li Y, et al (2024)

Prenatal acetaminophen exposure and the developing ovary: Time, dose, and course consequences for fetal mice.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 189:114679.

Acetaminophen is an emerging endocrine disrupting chemical and has been detected in various natural matrices. Numerous studies have documented developmental toxicity associated with prenatal acetaminophen exposure (PAcE). In this study, we established a PAcE Kunming mouse model at different time (middle pregnancy and third trimester), doses (low, middle, high) and courses (single or multi-) to systematically investigate their effects on fetal ovarian development. The findings indicated PAcE affected ovarian development, reduced fetal ovarian oocyte number and inhibited cell proliferation. A reduction in mRNA expression was observed for genes associated with oocyte markers (NOBOX and Figlα), follicular development markers (BMP15 and GDF9), and pre-granulosa cell steroid synthase (SF1 and StAR). Notably, exposure in middle pregnancy, high dose, multi-course resulted in the most pronounced inhibition of oocyte development; exposure in third trimester, high dose and multi-course led to the most pronounced inhibition of follicular development; and in third trimester, low dose and single course, the inhibition of pre-granulosa cell function was most pronounced. Mechanistic investigations revealed that PAcE had the most pronounced suppression of the ovarian Notch signaling pathway. Overall, PAcE caused fetal ovarian multicellular toxicity and inhibited follicular development with time, dose and course differences.

RevDate: 2024-04-25
CmpDate: 2024-04-24

Thomas F, Ujvari B, AM Dujon (2024)

[Evolution of cancer resistance in the animal kingdom].

Medecine sciences : M/S, 40(4):343-350.

Cancer is an inevitable collateral problem inherent in the evolution of multicellular organisms, which appeared at the end of the Precambrian. Faced to this constraint, a range of diverse anticancer defenses has evolved across the animal kingdom. Today, investigating how animal organisms, especially those of large size and long lifespan, manage cancer-related issues has both fundamental and applied outcomes, as it could inspire strategies for preventing or treating human cancers. In this article, we begin by presenting the conceptual framework for understanding evolutionary theories regarding the development of anti-cancer defenses. We then present a number of examples that have been extensively studied in recent years, including naked mole rats, elephants, whales, placozoa, xenarthras (such as sloths, armadillos and anteaters) and bats. The contributions of comparative genomics to understanding evolutionary convergences are also discussed. Finally, we emphasize that natural selection has also favored anti-cancer adaptations aimed at avoiding mutagenic environments, for example by maximizing immediate reproductive efforts in the event of cancer. Exploring these adaptive solutions holds promise for identifying novel approaches to improve human health.

RevDate: 2024-05-31
CmpDate: 2024-05-27

Daignan-Fornier B, T Pradeu (2024)

Critically assessing atavism, an evolution-centered and deterministic hypothesis on cancer.

BioEssays : news and reviews in molecular, cellular and developmental biology, 46(6):e2300221.

Cancer is most commonly viewed as resulting from somatic mutations enhancing proliferation and invasion. Some hypotheses further propose that these new capacities reveal a breakdown of multicellularity allowing cancer cells to escape proliferation and cooperation control mechanisms that were implemented during evolution of multicellularity. Here we critically review one such hypothesis, named "atavism," which puts forward the idea that cancer results from the re-expression of normally repressed genes forming a program, or toolbox, inherited from unicellular or simple multicellular ancestors. This hypothesis places cancer in an interesting evolutionary perspective that has not been widely explored and deserves attention. Thinking about cancer within an evolutionary framework, especially the major transitions to multicellularity, offers particularly promising perspectives. It is therefore of the utmost important to analyze why one approach that tries to achieve this aim, the atavism hypothesis, has not so far emerged as a major theory on cancer. We outline the features of the atavism hypothesis that, would benefit from clarification and, if possible, unification.

RevDate: 2024-04-25
CmpDate: 2024-04-12

Lindsey CR, Knoll AH, Herron MD, et al (2024)

Fossil-calibrated molecular clock data enable reconstruction of steps leading to differentiated multicellularity and anisogamy in the Volvocine algae.

BMC biology, 22(1):79.

BACKGROUND: Throughout its nearly four-billion-year history, life has undergone evolutionary transitions in which simpler subunits have become integrated to form a more complex whole. Many of these transitions opened the door to innovations that resulted in increased biodiversity and/or organismal efficiency. The evolution of multicellularity from unicellular forms represents one such transition, one that paved the way for cellular differentiation, including differentiation of male and female gametes. A useful model for studying the evolution of multicellularity and cellular differentiation is the volvocine algae, a clade of freshwater green algae whose members range from unicellular to colonial, from undifferentiated to completely differentiated, and whose gamete types can be isogamous, anisogamous, or oogamous. To better understand how multicellularity, differentiation, and gametes evolved in this group, we used comparative genomics and fossil data to establish a geologically calibrated roadmap of when these innovations occurred.

RESULTS: Our ancestral-state reconstructions, show that multicellularity arose independently twice in the volvocine algae. Our chronograms indicate multicellularity evolved during the Carboniferous-Triassic periods in Goniaceae + Volvocaceae, and possibly as early as the Cretaceous in Tetrabaenaceae. Using divergence time estimates we inferred when, and in what order, specific developmental changes occurred that led to differentiated multicellularity and oogamy. We find that in the volvocine algae the temporal sequence of developmental changes leading to differentiated multicellularity is much as proposed by David Kirk, and that multicellularity is correlated with the acquisition of anisogamy and oogamy. Lastly, morphological, molecular, and divergence time data suggest the possibility of cryptic species in Tetrabaenaceae.

CONCLUSIONS: Large molecular datasets and robust phylogenetic methods are bringing the evolutionary history of the volvocine algae more sharply into focus. Mounting evidence suggests that extant species in this group are the result of two independent origins of multicellularity and multiple independent origins of cell differentiation. Also, the origin of the Tetrabaenaceae-Goniaceae-Volvocaceae clade may be much older than previously thought. Finally, the possibility of cryptic species in the Tetrabaenaceae provides an exciting opportunity to study the recent divergence of lineages adapted to live in very different thermal environments.

RevDate: 2024-05-11
CmpDate: 2024-05-09

Wang H, Marucci G, Munke A, et al (2024)

High-resolution comparative atomic structures of two Giardiavirus prototypes infecting G. duodenalis parasite.

PLoS pathogens, 20(4):e1012140.

The Giardia lamblia virus (GLV) is a non-enveloped icosahedral dsRNA and endosymbiont virus that infects the zoonotic protozoan parasite Giardia duodenalis (syn. G. lamblia, G. intestinalis), which is a pathogen of mammals, including humans. Elucidating the transmission mechanism of GLV is crucial for gaining an in-depth understanding of the virulence of the virus in G. duodenalis. GLV belongs to the family Totiviridae, which infects yeast and protozoa intracellularly; however, it also transmits extracellularly, similar to the phylogenetically, distantly related toti-like viruses that infect multicellular hosts. The GLV capsid structure is extensively involved in the longstanding discussion concerning extracellular transmission in Totiviridae and toti-like viruses. Hence, this study constructed the first high-resolution comparative atomic models of two GLV strains, namely GLV-HP and GLV-CAT, which showed different intracellular localization and virulence phenotypes, using cryogenic electron microscopy single-particle analysis. The atomic models of the GLV capsids presented swapped C-terminal extensions, extra surface loops, and a lack of cap-snatching pockets, similar to those of toti-like viruses. However, their open pores and absence of the extra crown protein resemble those of other yeast and protozoan Totiviridae viruses, demonstrating the essential structures for extracellular cell-to-cell transmission. The structural comparison between GLV-HP and GLV-CAT indicates the first evidence of critical structural motifs for the transmission and virulence of GLV in G. duodenalis.

RevDate: 2024-04-09
CmpDate: 2024-04-08

Wang H, Guan Z, L Zheng (2024)

Single-cell RNA sequencing explores the evolution of the ecosystem from leukoplakia to head and neck squamous cell carcinoma.

Scientific reports, 14(1):8097.

It has been found that progression from leukoplakia to head and neck squamous cell carcinoma (HNSCC) is a long-term process that may involve changes in the multicellular ecosystem. We acquired scRNA-seq samples information from gene expression omnibus and UCSC Xena database. The BEAM function was used to construct the pseudotime trajectory and analyze the differentially expressed genes in different branches. We used the ssGSEA method to explore the correlation between each cell subgroup and survival time, and obtained the cell subgroup related to prognosis. During the progression from leukoplakia to HNSCC, we found several prognostic cell subgroups, such as AURKB + epithelial cells, SFRP1 + fibroblasts, SLC7A8 + macrophages, FCER1A + CD1C + dendritic cells, and TRGC2 + NK/T cells. All cell subgroups had two different fates, one tending to cell proliferation, migration, and enhancement of angiogenesis capacity, and the other tending to inflammatory immune response, leukocyte chemotaxis, and T cell activation. Tumor-promoting genes such as CD163 and CD209 were highly expressed in the myeloid cells, and depletion marker genes such as TIGIT, LAG3 were highly expressed in NK/T cells. Our study may provide a reference for the molecular mechanism of HNSCC and theoretical basis for the development of new therapeutic strategies.

RevDate: 2024-04-26
CmpDate: 2024-04-19

Deng Y, Xia L, Zhang J, et al (2024)

Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Cell reports. Medicine, 5(4):101489.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8[+] T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8[+] T cells, driven by specific stromal cells such as CTHCR1[+] fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8[+] T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

RevDate: 2024-04-09
CmpDate: 2024-04-09

Shao S, Liu K, Du J, et al (2024)

Functional characterization of serine proteinase inhibitor Kazal-Type in the red claw crayfish Cherax quadricarinatus.

Fish & shellfish immunology, 148:109525.

Serine protease inhibitors Kazal type (SPINKs) function in physiological and immunological processes across multicellular organisms. In the present study, we identified a SPINK gene, designated as CqSPINK, in the red claw crayfish Cherax quadricarinatus, which is the ortholog of human SPINK5. The deduced CqSPINK contains two Kazal domains consisting of 45 amino acid residues with a typical signature motif C-X3-C-X5-PVCG-X5-Y-X3-C-X6-C-X12-14-C. Each Kazal domain contains six conserved cysteine residues forming three pairs of disulfide bonds, segmenting the structure into three rings. Phylogenetic analysis revealed CqSPINK as a homolog of human SPINK5. CqSPINK expression was detected exclusively in hepatopancreas and epithelium, with rapid up-regulation in hepatopancreas upon Vibrio parahaemolyticus E1 challenge. Recombinant CqSPINK protein (rCqSPINK) was heterologously expressed in Escherichia coli and purified for further study. Proteinase inhibition assays demonstrated that rCqSPINK could potently inhibit proteinase K and subtilisin A, weakly inhibit α-chymotrypsin and elastase, but extremely weak inhibit trypsin. Furthermore, CqSPINK inhibited bacterial secretory proteinase activity from Bacillus subtilis, E. coli, and Staphylococcus aureus, and inhibited B. subtilis growth. These findings suggest CqSPINK's involvement in antibacterial immunity through direct inhibition of bacterial proteases, contributing to resistance against pathogen invasion.

RevDate: 2024-03-29
CmpDate: 2024-03-25

Phillips JE, D Pan (2024)

The Hippo kinase cascade regulates a contractile cell behavior and cell density in a close unicellular relative of animals.

eLife, 12:.

The genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organism Capsaspora owczarzaki. We previously showed that the Capsaspora ortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology of Capsaspora cell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki in Capsaspora, remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts in Capsaspora by generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing in coHpo and coWts mutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway kinase cascade and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.

RevDate: 2024-07-09
CmpDate: 2024-05-07

Brown AL, Meiborg AB, Franz-Wachtel M, et al (2024)

Characterization of the Pristionchus pacificus "epigenetic toolkit" reveals the evolutionary loss of the histone methyltransferase complex PRC2.

Genetics, 227(1):.

Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation-or lack thereof-of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the "epigenetic toolkit" available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with Caenorhabditis elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to compare with C. elegans. This inventory will enable reverse-genetic experiments related to plasticity and has revealed the first loss of PRC2 in a multicellular organism.

RevDate: 2024-03-19
CmpDate: 2024-03-18

Bing J, Guan Z, Zheng T, et al (2024)

Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection.

Nature communications, 15(1):2381.

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.

RevDate: 2024-06-03
CmpDate: 2024-05-31

Li X, Gao T, Ma X, et al (2024)

Extraction and identification of exosomes from three different sources of human ovarian granulosa cells and analysis of their differential miRNA expression profiles.

Journal of assisted reproduction and genetics, 41(5):1371-1385.

OBJECTIVE: As important functional cells in the ovary, ovarian granulosa cells are involved in the regulation of oocyte growth and development and play an important role in the study of female fertility preservation. Based on the importance of granulosa cell functionalism, in this study, we analyzed the exosome secretion capacity of human ovarian granulosa cells (SVOG/KGN-cell line, PGC-primary cells) and the differences in their miRNA expression.

METHODS: Cells were identified by hematoxylin-eosin staining (HE) and FSHR immunofluorescence staining; CCK8 and colony-forming assay were performed to compare cell proliferation capacity; exosomes were extracted and identified by ultra-high speed centrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot analysis (WB), and the expression profile of each cellular exosomal miRNA was analyzed by miRNA high-throughput sequencing.

RESULTS: The proliferative abilities of the three granulosa cells differed, but all had the ability to secrete exosomes. In the exosomes of SVOG, KGN, and PGC cells, 218, 327, and 471 miRNAs were detected, respectively. When compared to the exosomal miRNAs of PGC cells, 111 miRNAs were significantly different in SVOG, and 70 miRNAs were washed two significantly different in KGN cells. These differential miRNA functions were mainly enriched in the cell cycle, cell division/differentiation, multicellular biogenesis, and protein binding.

CONCLUSION: Human ovarian granulosa cells of different origins are capable of secreting exosomes, but there are still some differences in their exosomes and exosomal miRNAs, and experimental subjects should be selected rationally according to the actual situation.

RevDate: 2024-05-15
CmpDate: 2024-05-14

Pineau RM, Libby E, Demory D, et al (2024)

Emergence and maintenance of stable coexistence during a long-term multicellular evolution experiment.

Nature ecology & evolution, 8(5):1010-1020.

The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth's ecosystems. Yet little is known about how early steps in the evolution of multicellularity affect eco-evolutionary dynamics. Through long-term experimental evolution, we observed niche partitioning and the adaptive divergence of two specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subjected to selection for rapid growth, followed by selection favouring larger group size. Small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations, specializing on divergent aspects of a trade-off between growth rate and survival. Through modelling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically impactful emergent properties of this evolutionary transition.

RevDate: 2024-04-17
CmpDate: 2024-03-15

Wu Z, Liu D, Ou Y, et al (2024)

Mechanism and endoscopic-treatment-induced evolution of biliary non-anastomotic stricture after liver transplantation revealed by single-cell RNA sequencing.

Clinical and translational medicine, 14(3):e1622.

BACKGROUND: Biliary complications, especially non-anastomotic stricture (NAS), are the main complications after liver transplantation. Insufficient sampling and no recognized animal models obstruct the investigation. Thus, the mechanisms and alterations that occur during endoscopic treatment (ET) of NAS remain unclear.

METHODS: Samples were obtained with endoscopic forceps from the hilar bile ducts of NAS patients receiving continuous biliary stent implantation after diagnosis. Retrospective analysis of multiple studies indicated that the duration of ET for NAS was approximately 1-2 years. Thus, we divided the patients into short-term treatment (STT) and long-term treatment (LTT) groups based on durations of less or more than 1 year. Samples were subjected to single-cell RNA sequencing. Transcriptomic differences between STT and normal groups were defined as the NAS mechanism. Similarly, alterations from STT to LTT groups were regarded as endoscopic-treatment-induced evolution.

RESULTS: In NAS, inflammation and immune-related pathways were upregulated in different cell types, with nonimmune cells showing hypoxia pathway upregulation and immune cells showing ATP metabolism pathway upregulation, indicating heterogeneity. We confirmed a reduction in bile acid metabolism-related SPP1[+] epithelial cells in NAS. Increases in proinflammatory and profibrotic fibroblast subclusters indicated fibrotic progression in NAS. Furthermore, immune disorders in NAS were exacerbated by an increase in plasma cells and dysfunction of NK and NKT cells. ET downregulated multicellular immune and inflammatory responses and restored epithelial and endothelial cell proportions.

CONCLUSIONS: This study reveals the pathophysiological and genetic mechanisms and evolution of NAS induced by ET, thereby providing preventive and therapeutic insights into NAS.

HIGHLIGHTS: For the first time, single-cell transcriptome sequencing was performed on the bile ducts of patients with biliary complications. scRNA-seq analysis revealed distinct changes in the proportion and phenotype of multiple cell types during Nonanastomotic stricture (NAS) and endoscopic treatment. A reduction in bile acid metabolism-related SPP1+ epithelial cells and VEGFA+ endothelial cells, along with explosive infiltration of plasma cells and dysfunction of T and NK cells in NAS patients. SPP1+ macrophages and BST2+ T cells might serve as a surrogate marker for predicting endoscopic treatment.

RevDate: 2024-03-15
CmpDate: 2024-03-14

Jiménez-López D, Xoconostle-Cázares B, Calderón-Pérez B, et al (2024)

Evolutionary and Structural Analysis of PP16 in Viridiplantae.

International journal of molecular sciences, 25(5):.

Members of the phloem protein 16 (PP16) gene family are induced by elicitors in rice and the corresponding proteins from cucurbits, which display RNA binding and intercellular transport activities, are accumulated in phloem sap. These proteins facilitate the movement of protein complexes through the phloem translocation flow and may be involved in the response to water deficit, among other functions. However, there is scant information regarding their function in other plants, including the identification of paralog genes in non-vascular plants and chlorophytes. In the present work, an evolutionary and structural analysis of the PP16 family in green plants (Viridiplantae) was carried out. Data mining in different databases indicated that PP16 likely originated from a larger gene present in an ancestral lineage that gave rise to chlorophytes and multicellular plants. This gene encodes a protein related to synaptotagmin, which is involved in vesicular transport in animal systems, although other members of this family play a role in lipid turnover in endomembranes and organelles. These proteins contain a membrane-binding C2 domain shared with PP16 proteins in vascular plants. In silico analysis of the predicted structure of the PP16 protein family identified several β-sheets, one α-helix, and intrinsically disordered regions. PP16 may have been originally involved in vesicular trafficking and/or membrane maintenance but specialized in long-distance signaling during the emergence of the plant vascular system.

RevDate: 2024-08-06
CmpDate: 2024-05-23

Borland G, Wilkie SE, Thomson J, et al (2024)

Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan.

Aging cell, 23(5):e14141.

The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b[+/-]). We identified sexually dimorphic, organ-specific beneficial as well as detrimental effects of the Polr3b[+/-] mutation on health. Female Polr3b[+/-] mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, male Polr3b[+/-] mice were lighter than wild-type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor female Polr3b[+/-] mice were long-lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ- and sex-specific benefits for old-age health.

RevDate: 2024-08-21
CmpDate: 2024-03-05

Matsumoto H, M Ueda (2024)

Polarity establishment in the plant zygote at a glance.

Journal of cell science, 137(5):.

The complex structures of multicellular organisms originate from a unicellular zygote. In most angiosperms, including Arabidopsis thaliana, the zygote is distinctly polar and divides asymmetrically to produce an apical cell, which generates the aboveground part of the plant body, and a basal cell, which generates the root tip and extraembryonic suspensor. Thus, zygote polarity is pivotal for establishing the apical-basal axis running from the shoot apex to the root tip of the plant body. The molecular mechanisms and spatiotemporal dynamics behind zygote polarization remain elusive. However, advances in live-cell imaging of plant zygotes have recently made significant insights possible. In this Cell Science at a Glance article and the accompanying poster, we summarize our understanding of the early steps in apical-basal axis formation in Arabidopsis, with a focus on de novo transcriptional activation after fertilization and the intracellular dynamics leading to the first asymmetric division of the zygote.

RevDate: 2024-05-06
CmpDate: 2024-04-15

Deng S, Gong H, Zhang D, et al (2024)

A statistical method for quantifying progenitor cells reveals incipient cell fate commitments.

Nature methods, 21(4):597-608.

Quantifying the number of progenitor cells that found an organ, tissue or cell population is of fundamental importance for understanding the development and homeostasis of a multicellular organism. Previous efforts rely on marker genes that are specifically expressed in progenitors. This strategy is, however, often hindered by the lack of ideal markers. Here we propose a general statistical method to quantify the progenitors of any tissues or cell populations in an organism, even in the absence of progenitor-specific markers, by exploring the cell phylogenetic tree that records the cell division history during development. The method, termed targeting coalescent analysis (TarCA), computes the probability that two randomly sampled cells of a tissue coalesce within the tissue-specific monophyletic clades. The inverse of this probability then serves as a measure of the progenitor number of the tissue. Both mathematic modeling and computer simulations demonstrated the high accuracy of TarCA, which was then validated using real data from nematode, fruit fly and mouse, all with related cell phylogenetic trees. We further showed that TarCA can be used to identify lineage-specific upregulated genes during embryogenesis, revealing incipient cell fate commitments in mouse embryos.

RevDate: 2024-09-17
CmpDate: 2024-04-23

Iwaï H, Beyer HM, Johansson JEM, et al (2024)

The three-dimensional structure of the Vint domain from Tetrahymena thermophila suggests a ligand-regulated cleavage mechanism by the HINT fold.

FEBS letters, 598(8):864-874.

Vint proteins have been identified in unicellular metazoans as a novel hedgehog-related gene family, merging the von Willebrand factor type A domain and the Hedgehog/INTein (HINT) domains. We present the first three-dimensional structure of the Vint domain from Tetrahymena thermophila corresponding to the auto-processing domain of hedgehog proteins, shedding light on the unique features, including an adduct recognition region (ARR). Our results suggest a potential binding between the ARR and sulfated glycosaminoglycans like heparin sulfate. Moreover, we uncover a possible regulatory role of the ARR in the auto-processing by Vint domains, expanding our understanding of the HINT domain evolution and their use in biotechnological applications. Vint domains might have played a crucial role in the transition from unicellular to multicellular organisms.

RevDate: 2024-03-21
CmpDate: 2024-03-20

Földi C, Merényi Z, Balázs B, et al (2024)

Snowball: a novel gene family required for developmental patterning of fruiting bodies of mushroom-forming fungi (Agaricomycetes).

mSystems, 9(3):e0120823.

UNLABELLED: The morphogenesis of sexual fruiting bodies of fungi is a complex process determined by a genetically encoded program. Fruiting bodies reached the highest complexity levels in the Agaricomycetes; yet, the underlying genetics is currently poorly known. In this work, we functionally characterized a highly conserved gene termed snb1, whose expression level increases rapidly during fruiting body initiation. According to phylogenetic analyses, orthologs of snb1 are present in almost all agaricomycetes and may represent a novel conserved gene family that plays a substantial role in fruiting body development. We disrupted snb1 using CRISPR/Cas9 in the agaricomycete model organism Coprinopsis cinerea. snb1 deletion mutants formed unique, snowball-shaped, rudimentary fruiting bodies that could not differentiate caps, stipes, and lamellae. We took advantage of this phenotype to study fruiting body differentiation using RNA-Seq analyses. This revealed differentially regulated genes and gene families that, based on wild-type RNA-Seq data, were upregulated early during development and showed tissue-specific expression, suggesting a potential role in differentiation. Taken together, the novel gene family of snb1 and the differentially expressed genes in the snb1 mutants provide valuable insights into the complex mechanisms underlying developmental patterning in the Agaricomycetes.

IMPORTANCE: Fruiting bodies of mushroom-forming fungi (Agaricomycetes) are complex multicellular structures, with a spatially and temporally integrated developmental program that is, however, currently poorly known. In this study, we present a novel, conserved gene family, Snowball (snb), termed after the unique, differentiation-less fruiting body morphology of snb1 knockout strains in the model mushroom Coprinopsis cinerea. snb is a gene of unknown function that is highly conserved among agaricomycetes and encodes a protein of unknown function. A comparative transcriptomic analysis of the early developmental stages of differentiated wild-type and non-differentiated mutant fruiting bodies revealed conserved differentially expressed genes which may be related to tissue differentiation and developmental patterning fruiting body development.

RevDate: 2024-09-24
CmpDate: 2024-03-21

Wang R, Meng Q, Wang X, et al (2024)

Comparative genomic analysis of symbiotic and free-living Fluviibacter phosphoraccumulans strains provides insights into the evolutionary origins of obligate Euplotes-bacterial endosymbioses.

Applied and environmental microbiology, 90(3):e0190023.

UNLABELLED: Endosymbiosis is a widespread and important phenomenon requiring diverse model systems. Ciliates are a widespread group of protists that often form symbioses with diverse microorganisms. Endosymbioses between the ciliate Euplotes and heritable bacterial symbionts are common in nature, and four essential symbionts were described: Polynucleobacter necessarius, "Candidatus Protistobacter heckmanni," "Ca. Devosia symbiotica," and "Ca. Devosia euplotis." Among them, only the genus Polynucleobacter comprises very close free-living and symbiotic representatives, which makes it an excellent model for investigating symbiont replacements and recent symbioses. In this article, we characterized a novel endosymbiont inhabiting the cytoplasm of Euplotes octocarinatus and found that it is a close relative of the free-living bacterium Fluviibacter phosphoraccumulans (Betaproteobacteria and Rhodocyclales). We present the complete genome sequence and annotation of the symbiotic Fluviibacter. Comparative analyses indicate that the genome of symbiotic Fluviibacter is small in size and rich in pseudogenes when compared with free-living strains, which seems to fit the prediction for recently established endosymbionts undergoing genome erosion. Further comparative analysis revealed reduced metabolic capacities in symbiotic Fluviibacter, which implies that the symbiont relies on the host Euplotes for carbon sources, organic nitrogen and sulfur, and some cofactors. We also estimated substitution rates between symbiotic and free-living Fluviibacter pairs for 233 genes; the results showed that symbiotic Fluviibacter displays higher dN/dS mean value than free-living relatives, which suggested that genetic drift is the main driving force behind molecular evolution in endosymbionts.

IMPORTANCE: In the long history of symbiosis research, most studies focused mainly on organelles or bacteria within multicellular hosts. The single-celled protists receive little attention despite harboring an immense diversity of symbiotic associations with bacteria and archaea. One subgroup of the ciliate Euplotes species is strictly dependent on essential symbionts for survival and has emerged as a valuable model for understanding symbiont replacements and recent symbioses. However, almost all of our knowledge about the evolution and functions of Euplotes symbioses comes from the Euplotes-Polynucleobacter system. In this article, we report a novel essential symbiont, which also has very close free-living relatives. Genome analysis indicated that it is a recently established endosymbiont undergoing genome erosion and relies on the Euplotes host for many essential molecules. Our results provide support for the notion that essential symbionts of the ciliate Euplotes evolve from free-living progenitors in the natural water environment.

RevDate: 2024-07-12
CmpDate: 2024-07-12

Gupta P, Bermejo-Rodriguez C, Kocher H, et al (2024)

Chemotherapy Assessment in Advanced Multicellular 3D Models of Pancreatic Cancer: Unravelling the Importance of Spatiotemporal Mimicry of the Tumor Microenvironment.

Advanced biology, 8(7):e2300580.

Pancreatic ductal adenocarcinoma (PDAC) is a challenge for global health with very low survival rate and high therapeutic resistance. Hence, advanced preclinical models for treatment screening are of paramount importance. Herein, chemotherapeutic (gemcitabine) assessment on novel (polyurethane) scaffold-based spatially advanced 3D multicellular PDAC models is carried out. Through comprehensive image-based analysis at the protein level, and expression analysis at the mRNA level, the importance of stromal cells is confirmed, primarily activated stellate cells in the chemoresistance of PDAC cells within the models. Furthermore, it is demonstrated that, in addition to the presence of activated stellate cells, the spatial architecture of the scaffolds, i.e., segregation/compartmentalization of the cancer and stromal zones, affect the cellular evolution and is necessary for the development of chemoresistance. These results highlight that, further to multicellularity, mapping the tumor structure/architecture and zonal complexity in 3D cancer models is important for better mimicry of the in vivo therapeutic response.

RevDate: 2024-03-01
CmpDate: 2024-03-01

Mihalič F, Arcila D, Pettersson ME, et al (2024)

Conservation of Affinity Rather Than Sequence Underlies a Dynamic Evolution of the Motif-Mediated p53/MDM2 Interaction in Ray-Finned Fishes.

Molecular biology and evolution, 41(2):.

The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5 μM). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of "functional affinity" in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.

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ESP Quick Facts

ESP Origins

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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Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

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