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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 05 Jun 2020 at 01:46 Created: 

Mitochondrial Evolution

The endosymbiotic hypothesis for the origin of mitochondria (and chloroplasts) suggests that mitochondria are descended from specialized bacteria (probably purple nonsulfur bacteria) that somehow survived endocytosis by another species of prokaryote or some other cell type, and became incorporated into the cytoplasm.

Created with PubMed® Query: mitochondria AND evolution NOT 26799652[PMID] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2020-06-03

Tan M, Tol HTAV, Rosenkranz D, et al (2020)

PIWIL3 Forms a Complex with TDRKH in Mammalian Oocytes.

Cells, 9(6): pii:cells9061356.

P-element induced wimpy testis (PIWIs) are crucial guardians of genome integrity, particularly in germ cells. While mammalian PIWIs have been primarily studied in mouse and rat, a homologue for the human PIWIL3 gene is absent in the Muridae family, and hence the unique function of PIWIL3 in germ cells cannot be effectively modeled by mouse knockouts. Herein, we investigated the expression, distribution, and interaction of PIWIL3 in bovine oocytes. We localized PIWIL3 to mitochondria, and demonstrated that PIWIL3 expression is stringently controlled both spatially and temporally before and after fertilization. Moreover, we identified PIWIL3 in a mitochondrial-recruited three-membered complex with Tudor and KH domain-containing protein (TDRKH) and poly(A)-specific ribonuclease-like domain containing 1 (PNLDC1), and demonstrated by mutagenesis that PIWIL3 N-terminal arginines are required for complex assembly. Finally, we sequenced the piRNAs bound to PIWIL3-TDRKH-PNLDC1 and report here that about 50% of these piRNAs map to transposable elements, recapitulating the important role of PIWIL3 in maintaining genome integrity in mammalian oocytes.

RevDate: 2020-06-03

Mendoza H, Perlin MH, J Schirawski (2020)

Mitochondrial Inheritance in Phytopathogenic Fungi-Everything Is Known, or Is It?.

International journal of molecular sciences, 21(11): pii:ijms21113883.

Mitochondria are important organelles in eukaryotes that provide energy for cellular processes. Their function is highly conserved and depends on the expression of nuclear encoded genes and genes encoded in the organellar genome. Mitochondrial DNA replication is independent of the replication control of nuclear DNA and as such, mitochondria may behave as selfish elements, so they need to be controlled, maintained and reliably inherited to progeny. Phytopathogenic fungi meet with special environmental challenges within the plant host that might depend on and influence mitochondrial functions and services. We find that this topic is basically unexplored in the literature, so this review largely depends on work published in other systems. In trying to answer elemental questions on mitochondrial functioning, we aim to introduce the aspect of mitochondrial functions and services to the study of plant-microbe-interactions and stimulate phytopathologists to consider research on this important organelle in their future projects.

RevDate: 2020-06-02

Gaff DF, M Oliver (2013)

The evolution of desiccation tolerance in angiosperm plants: a rare yet common phenomenon.

Functional plant biology : FPB, 40(4):315-328.

In a minute proportion of angiosperm species, rehydrating foliage can revive from airdryness or even from equilibration with air of ~0% RH. Such desiccation tolerance is known from vegetative cells of some species of algae and of major groups close to the evolutionary path of the angiosperms. It is also found in the reproductive structures of some algae, moss spores and probably the aerial spores of other terrestrial cryptogamic taxa. The occurrence of desiccation tolerance in the seed plants is overwhelmingly in the aerial reproductive structures; the pollen and seed embryos. Spatially and temporally, pollen and embryos are close ontogenetic derivatives of the angiosperm microspores and megaspores respectively. This suggests that the desiccation tolerance of pollen and embryos derives from the desiccation tolerance of the spores of antecedent taxa and that the basic pollen/embryo mechanism of desiccation tolerance has eventually become expressed also in the vegetative tissue of certain angiosperm species whose drought avoidance is inadequate in micro-habitats that suffer extremely xeric episodes. The protective compounds and processes that contribute to desiccation tolerance in angiosperms are found in the modern groups related to the evolutionary path leading to the angiosperms and are also present in the algae and in the cyanobacteria. The mechanism of desiccation tolerance in the angiosperms thus appears to have its origins in algal ancestors and possibly in the endosymbiotic cyanobacteria-related progenitor of chloroplasts and the bacteria-related progenitor of mitochondria. The mechanism may involve the regulation and timing of the accumulation of protective compounds and of other contributing substances and processes.

RevDate: 2020-06-03
CmpDate: 2020-06-03

Liu W, Cai Y, Zhang Q, et al (2020)

Subchromosome-Scale Nuclear and Complete Mitochondrial Genome Characteristics of Morchella crassipes.

International journal of molecular sciences, 21(2):.

Morchella crassipes (Vent.) Pers., a typical yellow morel species with high economic value, is mainly distributed in the low altitude plains of Eurasia. However, rare research has been performed on its genomics and polarity, thus limiting its research and development. Here, we reported a fine physical map of the nuclear genome at the subchromosomal-scale and the complete mitochondrial genome of M. crassipes. The complete size of the nuclear genome was 56.7 Mb, and 23 scaffolds were assembled, with eight of them being complete chromosomes. A total of 11,565 encoding proteins were predicted. The divergence time analysis showed that M. crassipes representing yellow morels differentiated with black morels at ~33.98 Mya (million years), with 150 gene families contracted and expanded in M. crassipes versus the two black morels (M. snyderi and M. importuna). Furthermore, 409 CAZYme genes were annotated in M. crassipes, containing almost all plant cell wall degrading enzymes compared with the mycorrhizal fungi (truffles). Genomic annotation of mating type loci and amplification of the mating genes in the monospore population was conducted, the results indicated that M. crassipes is a heterothallic fungus. Additionally, a complete circular mitochondrial genome of M. crassipes was assembled, the size reached as large as 531,195 bp. It can be observed that the strikingly large size was the biggest up till now, coupled with 14 core conserved mitochondrial protein-coding genes, two rRNAs, 31 tRNAs, 51 introns, and 412 ncORFs. The total length of intron sequences accounted for 53.67% of the mitochondrial genome, with 19 introns having a length over 5 kb. Particularly, 221 of 412 ncORFs were distributed within 51 introns, and the total length of the ncORFs sequence accounted for 40.83% of the mitochondrial genome, and 297 ncORFs had expression activity in the mycelium stage, suggesting their potential functions in M. crassipes. Meanwhile, there was a high degree of repetition (51.31%) in the mitochondria of M. crassipes. Thus, the large number of introns, ncORFs and internal repeat sequences may contribute jointly to the largest fungal mitochondrial genome to date. The fine physical maps of nuclear genome and mitochondrial genome obtained in this study will open a new door for better understanding of the mysterious species of M. crassipes.

RevDate: 2020-06-01

Gibellini L, De Gaetano A, Mandrioli M, et al (2020)

The biology of Lonp1: More than a mitochondrial protease.

International review of cell and molecular biology, 354:1-61.

Initially discovered as a protease responsible for degradation of misfolded or damaged proteins, the mitochondrial Lon protease (Lonp1) turned out to be a multifaceted enzyme, that displays at least three different functions (proteolysis, chaperone activity, binding of mtDNA) and that finely regulates several cellular processes, within and without mitochondria. Indeed, LONP1 in humans is ubiquitously expressed, and is involved in regulation of response to oxidative stress and, heat shock, in the maintenance of mtDNA, in the regulation of mitophagy. Furthermore, its proteolytic activity can regulate several biochemical pathways occurring totally or partially within mitochondria, such as TCA cycle, oxidative phosphorylation, steroid and heme biosynthesis and glutamine production. Because of these multiple activities, Lon protease is highly conserved throughout evolution, and mutations occurring in its gene determines severe diseases in humans, including a rare syndrome characterized by Cerebral, Ocular, Dental, Auricular and Skeletal anomalies (CODAS). Finally, alterations of LONP1 regulation in humans can favor tumor progression and aggressiveness, further highlighting the crucial role of this enzyme in mitochondrial and cellular homeostasis.

RevDate: 2020-05-28
CmpDate: 2020-05-28

Sun JT, Duan XZ, Hoffmann AA, et al (2019)

Mitochondrial variation in small brown planthoppers linked to multiple traits and probably reflecting a complex evolutionary trajectory.

Molecular ecology, 28(14):3306-3323.

While it has been proposed in several taxa that the mitochondrial genome is associated with adaptive evolution to different climatic conditions, making links between mitochondrial haplotypes and organismal phenotypes remains a challenge. Mitonuclear discordance occurs in the small brown planthopper (SBPH), Laodelphax striatellus, with one mitochondrial haplogroup (HGI) more common in the cold climate region of China relative to another form (HGII) despite strong nuclear gene flow, providing a promising model to investigate climatic adaptation of mitochondrial genomes. We hypothesized that cold adaptation through HGI may be involved, and considered mitogenome evolution, population genetic analyses, and bioassays to test this hypothesis. In contrast to our hypothesis, chill-coma recovery tests and population genetic tests of selection both pointed to HGII being involved in cold adaptation. Phylogenetic analyses revealed that HGII is nested within HGI, and has three nonsynonymous changes in ND2, ND5 and CYTB in comparison to HGI. These molecular changes likely increased mtDNA copy number, cold tolerance and fecundity of SBPH, particularly through a function-altering amino acid change involving M114T in ND2. Nuclear background also influenced fecundity and chill recovery (i.e., mitonuclear epistasis) and protein modelling indicates possible nuclear interactions for the two nonsynonymous changes in ND2 and CYTB. The high occurrence frequency of HGI in the cold climate region of China remains unexplained, but several possible reasons are discussed. Overall, our study points to a link between mtDNA variation and organismal-level evolution and suggests a possible role of mitonuclear interactions in maintaining mtDNA diversity.

RevDate: 2020-05-25
CmpDate: 2020-05-25

Guièze R, Liu VM, Rosebrock D, et al (2019)

Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies.

Cancer cell, 36(4):369-384.e13.

Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved B cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance.

RevDate: 2020-05-25
CmpDate: 2020-05-25

Bernardo PH, Sánchez-Ramírez S, Sánchez-Pacheco SJ, et al (2019)

Extreme mito-nuclear discordance in a peninsular lizard: the role of drift, selection, and climate.

Heredity, 123(3):359-370.

Nuclear and mitochondrial genomes coexist within cells but are subject to different tempos and modes of evolution. Evolutionary forces such as drift, mutation, selection, and migration are expected to play fundamental roles in the origin and maintenance of diverged populations; however, divergence may lag between genomes subject to different modes of inheritance and functional specialization. Herein, we explore whole mitochondrial genome data and thousands of nuclear single nucleotide polymorphisms to evidence extreme mito-nuclear discordance in the small black-tailed brush lizard, Urosaurus nigricaudus, of the Peninsula of Baja California, Mexico and southern California, USA, and discuss potential drivers. Results show three deeply divergent mitochondrial lineages dating back to the later Miocene (ca. 5.5 Ma) and Pliocene (ca. 2.8 Ma) that likely followed geographic isolation due to trans-peninsular seaways. This contrasts with very low levels of genetic differentiation in nuclear loci (FST < 0.028) between mtDNA lineages. Analyses of protein-coding genes reveal substantial fixed variation between mitochondrial lineages, of which a significant portion comes from non-synonymous mutations. A mixture of drift and selection is likely responsible for the rise of these mtDNA groups, albeit with little evidence of marked differences in climatic niche space between them. Finally, future investigations can look further into the role that mito-nuclear incompatibilities and mating systems play in explaining contrasting nuclear gene flow.

RevDate: 2020-05-22

Neveu E, Khalifeh D, Salamin N, et al (2020)

Prototypic SNARE Proteins Are Encoded in the Genomes of Heimdallarchaeota, Potentially Bridging the Gap between the Prokaryotes and Eukaryotes.

Current biology : CB pii:S0960-9822(20)30576-5 [Epub ahead of print].

A defining feature of eukaryotic cells is the presence of numerous membrane-bound organelles that subdivide the intracellular space into distinct compartments. How the eukaryotic cell acquired its internal complexity is still poorly understood. Material exchange among most organelles occurs via vesicles that bud off from a source and specifically fuse with a target compartment. Central players in the vesicle fusion process are the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. These small tail-anchored (TA) membrane proteins zipper into elongated four-helix bundles that pull membranes together. SNARE proteins are highly conserved among eukaryotes but are thought to be absent in prokaryotes. Here, we identified SNARE-like factors in the genomes of uncultured organisms of Asgard archaea of the Heimdallarchaeota clade, which are thought to be the closest living relatives of eukaryotes. Biochemical experiments show that the archaeal SNARE-like proteins can interact with eukaryotic SNARE proteins. We did not detect SNAREs in α-proteobacteria, the closest relatives of mitochondria, but identified several genes encoding for SNARE proteins in γ-proteobacteria of the order Legionellales, pathogens that live inside eukaryotic cells. Very probably, their SNAREs stem from lateral gene transfer from eukaryotes. Together, this suggests that the diverse set of eukaryotic SNAREs evolved from an archaeal precursor. However, whether Heimdallarchaeota actually have a simplified endomembrane system will only be seen when we succeed studying these organisms under the microscope.

RevDate: 2020-05-22

Roulet ME, Garcia LE, Gandini CL, et al (2020)

Multichromosomal structure and foreign tracts in the Ombrophytum subterraneum (Balanophoraceae) mitochondrial genome.

Plant molecular biology pii:10.1007/s11103-020-01014-x [Epub ahead of print].

Horizontal gene transfer (HGT) is frequent in parasitic plant mitochondria as a result of vascular connections established in host-parasite relationships. Recent studies of the holoparasitic plant Lophophytum mirabile (Balanophoraceae) revealed the unprecedented acquisition of a large amount of mitochondrial sequences from its legume host. We focused on a close relative, the generalist holoparasite Ombrophytum subterraneum, to examine the incidence of HGT events in the mitochondrial genome (mtDNA). The mtDNA of O. subterraneum assembles into 54 circular chromosomes, only 34 of which contain the 51 full-length coding regions. Numerous foreign tracts (totaling almost 100 kb, ~ 14% of the mtDNA), including 12 intact genes, were acquired by HGT from the Asteraceae hosts. Nine chromosomes concentrate most of those regions and eight are almost entirely foreign. Native homologs of each foreign gene coexist in the mtDNA and are potentially functional. A large proportion of shorter regions were related to the Fabaceae (a total of ~ 110 kb, 15.4%), some of which were shared with L. mirabile. We also found evidence of foreign sequences donated by angiosperm lineages not reported as hosts (Apocynaceae, Euphorbiaceae, Lamiaceae, and Malvales). We propose an evolutionary hypothesis that involves ancient transfers from legume hosts in the common ancestor of Ombrophytum and Lophophytum followed by more recent transfer events in L. mirabile. Besides, the O. subterraneum mtDNA was also subjected to additional HGT events from diverse angiosperm lineages, including large and recent transfers from the Asteraceae, and also from Lamiaceae.

RevDate: 2020-05-20

Speijer D, Hammond M, J Lukeš (2020)

Comparing Early Eukaryotic Integration of Mitochondria and Chloroplasts in the Light of Internal ROS Challenges: Timing is of the Essence.

mBio, 11(3): pii:mBio.00955-20.

When trying to reconstruct the evolutionary trajectories during early eukaryogenesis, one is struck by clear differences in the developments of two organelles of endosymbiotic origin: the mitochondrion and the chloroplast. From a symbiogenic perspective, eukaryotic development can be interpreted as a process in which many of the defining eukaryotic characteristics arose as a result of mutual adaptions of both prokaryotes (an archaeon and a bacterium) involved. This implies that many steps during the bacterium-to-mitochondrion transition trajectory occurred in an intense period of dramatic and rapid changes. In contrast, the subsequent cyanobacterium-to-chloroplast development in a specific eukaryotic subgroup, leading to the photosynthetic lineages, occurred in a full-fledged eukaryote. The commonalities and differences in the two trajectories shed an interesting light on early, and ongoing, eukaryotic evolutionary driving forces, especially endogenous reactive oxygen species (ROS) formation. Differences between organellar ribosomes, changes to the electron transport chain (ETC) components, and mitochondrial codon reassignments in nonplant mitochondria can be understood when mitochondrial ROS formation, e.g., during high energy consumption in heterotrophs, is taken into account.IMPORTANCE The early eukaryotic evolution was deeply influenced by the acquisition of two endosymbiotic organelles - the mitochondrion and the chloroplast. Here we discuss the possibly important role of reactive oxygen species in these processes.

RevDate: 2020-05-19

Pánek T, Eliáš M, Vancová M, et al (2020)

Returning to the Fold for Lessons in Mitochondrial Crista Diversity and Evolution.

Current biology : CB, 30(10):R575-R588.

Cristae are infoldings of the mitochondrial inner membrane jutting into the organelle's innermost compartment from narrow stems at their base called crista junctions. They are emblematic of aerobic mitochondria, being the fabric for the molecular machinery driving cellular respiration. Electron microscopy revealed that diverse eukaryotes possess cristae of different shapes. Yet, crista diversity has not been systematically examined in light of our current knowledge about eukaryotic evolution. Since crista form and function are intricately linked, we take a holistic view of factors that may underlie both crista diversity and the adherence of cristae to a recognizable form. Based on electron micrographs of 226 species from all major lineages, we propose a rational crista classification system that postulates cristae as variations of two general morphotypes: flat and tubulo-vesicular. The latter is most prevalent and likely ancestral, but both morphotypes are found interspersed throughout the eukaryotic tree. In contrast, crista junctions are remarkably conserved, supporting their proposed role as diffusion barriers that sequester cristae contents. Since cardiolipin, ATP synthase dimers, the MICOS complex, and dynamin-like Opa1/Mgm1 are known to be involved in shaping cristae, we examined their variation in the context of crista diversity. Moreover, we have identified both commonalities and differences that may collectively be manifested as diverse variations of crista form and function.

RevDate: 2020-05-19

Lane N (2020)

How energy flow shapes cell evolution.

Current biology : CB, 30(10):R471-R476.

How mitochondria shaped the evolution of eukaryotic complexity has been controversial for decades. The discovery of the Asgard archaea, which harbor close phylogenetic ties to the eukaryotes, supports the idea that a critical endosymbiosis between an archaeal host and a bacterial endosymbiont transformed the selective constraints present at the origin of eukaryotes. Cultured Asgard archaea are typically prokaryotic in both size and internal morphology, albeit featuring extensive protrusions. The acquisition of the mitochondrial predecessor by an archaeal host cell fundamentally altered the topology of genes in relation to bioenergetic membranes. Mitochondria internalised not only the bioenergetic membranes but also the genetic machinery needed for local control of oxidative phosphorylation. Gene loss from mitochondria enabled expansion of the nuclear genome, giving rise to an extreme genomic asymmetry that is ancestral to all extant eukaryotes. This genomic restructuring gave eukaryotes thousands of fold more energy availability per gene. In principle, that difference can support more and larger genes, far more non-coding DNA, greater regulatory complexity, and thousands of fold more protein synthesis per gene. These changes released eukaryotes from the bioenergetic constraints on prokaryotes, facilitating the evolution of morphological complexity.

RevDate: 2020-05-19

He Q, Luo J, Xu JZ, et al (2020)

Characterization of Hsp70 gene family provides insight into its functions related to microsporidian proliferation.

Journal of invertebrate pathology pii:S0022-2011(20)30100-2 [Epub ahead of print].

Heat shock protein 70 (Hsp70), a highly conserved protein family, is widely distributed in organisms and plays fundamental roles in biotic and abiotic stress responses. However, reports on Hsp70 genes are scarce in microsporidia, a very large group of obligate intracellular parasites that can infect nearly all animals, including humans. In this study, we identified 37 Hsp70 proteins from eight microsporidian genomes and classified them into four subfamilies (A-D). The number of Hsp70 genes in these microsporidia was significantly fewer than in Rozella allomycis and yeast. All microsporidian species contained genes from each subfamily and similar subcellular locations (mitochondria, endoplasmic reticulum, cytosol, and cytosol and/or nucleus), indicating that each Hsp70 member may fulfil distinct functions. The conserved structures and motifs of the Hsp70 proteins in the same subfamily were highly similar. Expression analysis indicated that the subfamily C cytosol (cyto)-associated Hsp70s is functional during microsporidia development. Immunofluorescence assays revealed that Cyto-NbHsp70 was cytoplasmically located in the proliferation-stage of Nosema bombycis. Cyto-NbHsp70 antiserum also labeled Encephalitozoon hellem within infected cells, suggesting that this antiserum is a potential molecular marker for labeling the proliferative phases of different microsporidian species. The propagation of N. bombycis was significantly inhibited following RNAi of Cyto-NbHsp70, indicating that Cyto-NbHsp70 is important for pathogen proliferation. Our phylogenetic data suggest that Hsp70 proteins evolved during microsporidia adaption to intracellular parasitism, and they play important roles in pathogen development.

RevDate: 2020-05-20
CmpDate: 2020-05-20

Moraes CT (2019)

Sorting mtDNA Species-the Role of nDNA-mtDNA Co-evolution.

Cell metabolism, 30(6):1002-1004.

The segregation of heteroplasmic mtDNA species was thought to be mostly stochastic. However, recent findings, including a study by Latorre-Pellicer et al. (2019) published in this issue of Cell Metabolism, provide evidence that nuclear DNA and mitochondrial DNA interactions play an important role in the sorting process.

RevDate: 2020-05-20
CmpDate: 2020-05-20

Wang S, Jiao N, Zhao L, et al (2020)

Evidence for the paternal mitochondrial DNA in the crucian carp-like fish lineage with hybrid origin.

Science China. Life sciences, 63(1):102-115.

In terms of taxonomic status, common carp (Cyprinus carpio, Cyprininae) and crucian carp (Carassius auratus, Cyprininae) are different species; however, in this study, a newborn homodiploid crucian carp-like fish (2n=100) (2nNCRC) lineage (F1-F3) was established from the interspecific hybridization of female common carp (2n=100)×male blunt snout bream (Megalobrama amblycephala, Cultrinae, 2n=48). The phenotypes and genotypes of 2nNCRC differed from those of its parents but were closely related to those of the existing diploid crucian carp. We further sequenced the whole mitochondrial (mt) genomes of the 2nNCRC lineage from F1 to F3. The paternal mtDNA fragments were stably embedded in the mt-genomes of F1-F3 generations of 2nNCRC to form chimeric DNA fragments. Along with this chimeric process, numerous base sites of F1-F3 generations of 2nNCRC underwent mutations. Most of these mutation sites were consistent with the existing diploid crucian carp. Moreover, the mtDNA organization and nucleotide composition of 2nNCRC were more similar to those of the existing diploid crucian carp than those of the parents. The inheritable chimeric DNA fragments and mutant loci in the mt-genomes of different generations of 2nNCRC provided important evidence of the mtDNA change process in the newborn lineage derived from hybridization of different species. Our findings demonstrated for the first time that the paternal mtDNA were transmitted into the mt-genomes of homodiploid lineage, which provided new insights into the existence of paternal mtDNA in the mtDNA inheritance.

RevDate: 2020-05-15

Arad M, Waldman M, Abraham NG, et al (2020)

Therapeutic approaches to diabetic cardiomyopathy: Targeting the antioxidant pathway.

Prostaglandins & other lipid mediators pii:S1098-8823(20)30047-2 [Epub ahead of print].

The global epidemic of cardiovascular disease continues unabated and remains the leading cause of death both in the US and worldwide. In the current review we summarize the available therapies for diabetes and cardiovascular disease in diabetics. Clearly, the current approaches to diabetic heart disease often target the manifestations and certain mediators but not the specific pathways leading to myocardial injury, remodeling and dysfunction. Better understanding of the molecular events determining the evolution of diabetic cardiomyopathy will provide insight into the development of specific and targeted therapies. This review reflects a dramatic increase in understanding the role of enhanced inflammatory response, ROS production, fibrosis in diabetic heart, as well as the contribution of Cyp-P450-epoxygenase-derived epoxyeicosatrienoic acid (EET), Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α (PGC-1α), Heme Oxygenase (HO)-1 and 20-HETE in pathophysiology and therapy of cardiovascular disease. PGC-1α increases production of the HO-1 which has a major role in protecting the heart against oxidative stress, microcirculation and mitochondrial dysfunction. This review focuses on potential drugs and their downstream targets, PGC-1α and HO-1, as major loci for developing therapeutic approaches beside diet and lifestyle modification for the treatment and prevention of heart disease associated with obesity and diabetes.

RevDate: 2020-05-15

Fonseca PLC, Badotti F, De-Paula RB, et al (2020)

Exploring the Relationship Among Divergence Time and Coding and Non-coding Elements in the Shaping of Fungal Mitochondrial Genomes.

Frontiers in microbiology, 11:765.

The order Hypocreales (Ascomycota) is composed of ubiquitous and ecologically diverse fungi such as saprobes, biotrophs, and pathogens. Despite their phylogenetic relationship, these species exhibit high variability in biomolecules production, lifestyle, and fitness. The mitochondria play an important role in the fungal biology, providing energy to the cells and regulating diverse processes, such as immune response. In spite of its importance, the mechanisms that shape fungal mitogenomes are still poorly understood. Herein, we investigated the variability and evolution of mitogenomes and its relationship with the divergence time using the order Hypocreales as a study model. We sequenced and annotated for the first time Trichoderma harzianum mitochondrial genome (mtDNA), which was compared to other 34 mtDNAs species that were publicly available. Comparative analysis revealed a substantial structural and size variation on non-coding mtDNA regions, despite the conservation of copy number, length, and structure of protein-coding elements. Interestingly, we observed a highly significant correlation between mitogenome length, and the number and size of non-coding sequences in mitochondrial genome. Among the non-coding elements, group I and II introns and homing endonucleases genes (HEGs) were the main contributors to discrepancies in mitogenomes structure and length. Several intronic sequences displayed sequence similarity among species, and some of them are conserved even at gene position, and were present in the majority of mitogenomes, indicating its origin in a common ancestor. On the other hand, we also identified species-specific introns that advocate for the origin by different mechanisms. Investigation of mitochondrial gene transfer to the nuclear genome revealed that nuclear copies of the nad5 are the most frequent while atp8, atp9, and cox3 could not be identified in any of the nuclear genomes analyzed. Moreover, we also estimated the divergence time of each species and investigated its relationship with coding and non-coding elements as well as with the length of mitogenomes. Altogether, our results demonstrated that introns and HEGs are key elements on mitogenome shaping and its presence on fast-evolving mtDNAs could be mostly explained by its divergence time, although the intron sharing profile suggests the involvement of other mechanisms on the mitochondrial genome evolution, such as horizontal transference.

RevDate: 2020-05-15
CmpDate: 2020-05-15

Sinha S, N Manoj (2019)

Molecular evolution of proteins mediating mitochondrial fission-fusion dynamics.

FEBS letters, 593(7):703-718.

Eukaryotes employ a subset of dynamins to mediate mitochondrial fusion and fission dynamics. Here we report the molecular evolution and diversification of the dynamin-related mitochondrial proteins that drive the fission (Drp1) and the fusion processes (mitofusin and OPA1). We demonstrate that the three paralogs emerged concurrently in an early mitochondriate eukaryotic ancestor. Furthermore, multiple independent duplication events from an ancestral bifunctional fission protein gave rise to specialized fission proteins. The evolutionary history of these proteins is marked by transformations that include independent gain and loss events occurring at the levels of entire genes, specific functional domains, and intronic regions. The domain level variations primarily comprise loss-gain of lineage specific domains that are present in the terminal regions of the sequences.

RevDate: 2020-05-14

Diroma MA, Varvara AS, Attimonelli M, et al (2020)

Investigating Human Mitochondrial Genomes in Single Cells.

Genes, 11(5): pii:genes11050534.

Mitochondria host multiple copies of their own small circular genome that has been extensively studied to trace the evolution of the modern eukaryotic cell and discover important mutations linked to inherited diseases. Whole genome and exome sequencing have enabled the study of mtDNA in a large number of samples and experimental conditions at single nucleotide resolution, allowing the deciphering of the relationship between inherited mutations and phenotypes and the identification of acquired mtDNA mutations in classical mitochondrial diseases as well as in chronic disorders, ageing and cancer. By applying an ad hoc computational pipeline based on our MToolBox software, we reconstructed mtDNA genomes in single cells using whole genome and exome sequencing data obtained by different amplification methodologies (eWGA, DOP-PCR, MALBAC, MDA) as well as data from single cell Assay for Transposase Accessible Chromatin with high-throughput sequencing (scATAC-seq) in which mtDNA sequences are expected as a byproduct of the technology. We show that assembled mtDNAs, with the exception of those reconstructed by MALBAC and DOP-PCR methods, are quite uniform and suitable for genomic investigations, enabling the study of various biological processes related to cellular heterogeneity such as tumor evolution, neural somatic mosaicism and embryonic development.

RevDate: 2020-05-14
CmpDate: 2020-05-14

Mereu P, Pirastru M, Satta V, et al (2019)

Mitochondrial D-loop Sequence Variability in Three Native Insular Griffon Vulture (Gyps fulvus) Populations from the Mediterranean Basin.

BioMed research international, 2019:2073919.

The islands of Sardinia, Crete, and Cyprus are hosting the last native insular griffon populations in the Mediterranean basin. Their states have been evaluated from "vulnerable" to "critically endangered". The sequence analysis of molecular markers, particularly the mtDNA D-loop region, provides useful information in studying the evolution of closely related taxa and the conservation of endangered species. Therefore, a study of D-loop region sequence was carried out to estimate the genetic diversity and phylogenetic relationship within and among these three populations. Among 84 griffon specimens (44 Sardinian, 33 Cretan, and 7 Cypriot), we detected four haplotypes including a novel haplotype (HPT-D) that was exclusively found in the Cretan population with a frequency of 6.1%. When considered as a unique population, haplotype diversity (Hd) and nucleotide diversity (π) were high at 0.474 and 0.00176, respectively. A similar level of Hd and π was found in Sardinian and Cretan populations, both showing three haplotypes. The different haplotype frequencies and exclusivity detected were in accordance with the limited matrilineal gene flow (FST = 0.07097), probably related to the species reluctance to fly over sea masses. The genetic variability we observe today would therefore be the result of an evolutionary process strongly influenced by isolation leading to the appearance of island variants which deserve to be protected. Furthermore, since nesting sites and food availability are essential elements for colony settlement, we may infer that the island's colonization began when the first domestic animals were transferred by humans during the Neolithic. In conclusion, our research presents a first contribution to the genetic characterization of the griffon vulture populations in the Mediterranean islands of Sardinia, Crete and Cyprus and lays the foundation for conservation and restocking programs.

RevDate: 2020-05-14
CmpDate: 2020-05-14

Prous M, Lee KM, M Mutanen (2020)

Cross-contamination and strong mitonuclear discordance in Empria sawflies (Hymenoptera, Tenthredinidae) in the light of phylogenomic data.

Molecular phylogenetics and evolution, 143:106670.

In several sawfly taxa strong mitonuclear discordance has been observed, with nuclear genes supporting species assignments based on morphology, whereas the barcode region of the mitochondrial COI gene suggests different relationships. As previous studies were based on only a few nuclear genes, the causes and the degree of mitonuclear discordance remain ambiguous. Here, we obtained genomic-scale ddRAD data together with Sanger sequences of mitochondrial COI and two to three nuclear protein coding genes to investigate species limits and mitonuclear discordance in two closely related species groups of the sawfly genus Empria. As found previously based on nuclear ITS and mitochondrial COI sequences, species are in most cases supported as monophyletic based on new nuclear data reported here, but not based on mitochondrial COI. This mitonuclear discordance can be explained by occasional mitochondrial introgression with little or no nuclear gene flow, a pattern that might be common in haplodiploid taxa with slowly evolving mitochondrial genomes. Some species in the E. immersa group are not recovered as monophyletic according to either mitochondrial or nuclear data, but this could partly be because of unresolved taxonomy. Preliminary analyses of ddRAD data did not recover monophyly of E. japonica within the E. longicornis group (three Sanger sequenced nuclear genes strongly supported monophyly), but closer examination of the data and additional Sanger sequencing suggested that both specimens were substantially (possibly 10-20% of recovered loci) cross-contaminated. A reason could be specimen identification tag jumps during sequencing library preparation that in previous studies have been shown to affect up to 2.5% of the sequenced reads. We provide an R script to examine patterns of identical loci among the specimens and estimate that the cross-contamination rate is not unusually high for our ddRAD dataset as a whole (based on counting of identical sequences in the immersa and longicornis groups, which are well separated from each other and probably do not hybridise). The high rate of cross-contamination for both E. japonica specimens might be explained by the small number of recovered loci (~1000) compared to most other specimens (>10 000 in some cases) because of poor sequencing results. We caution against drawing unexpected biological conclusions when closely related specimens are pooled before sequencing and tagged only at one end of the molecule or at both ends using a unique combination of limited number of tags (less than the number of specimens).

RevDate: 2020-05-14
CmpDate: 2020-05-14

Greiner S, Lehwark P, R Bock (2019)

OrganellarGenomeDRAW (OGDRAW) version 1.3.1: expanded toolkit for the graphical visualization of organellar genomes.

Nucleic acids research, 47(W1):W59-W64.

Organellar (plastid and mitochondrial) genomes play an important role in resolving phylogenetic relationships, and next-generation sequencing technologies have led to a burst in their availability. The ongoing massive sequencing efforts require software tools for routine assembly and annotation of organellar genomes as well as their display as physical maps. OrganellarGenomeDRAW (OGDRAW) has become the standard tool to draw graphical maps of plastid and mitochondrial genomes. Here, we present a new version of OGDRAW equipped with a new front end. Besides several new features, OGDRAW now has access to a local copy of the organelle genome database of the NCBI RefSeq project. Together with batch processing of (multi-)GenBank files, this enables the user to easily visualize large sets of organellar genomes spanning entire taxonomic clades. The new OGDRAW server can be accessed at

RevDate: 2020-05-13

Kleczewska M, Grabinska A, Jelen M, et al (2020)

Biochemical Convergence of Mitochondrial Hsp70 System Specialized in Iron-Sulfur Cluster Biogenesis.

International journal of molecular sciences, 21(9): pii:ijms21093326.

Mitochondria play a central role in the biogenesis of iron-sulfur cluster(s) (FeS), protein cofactors needed for many cellular activities. After assembly on scaffold protein Isu, the cluster is transferred onto a recipient apo-protein. Transfer requires Isu interaction with an Hsp70 chaperone system that includes a dedicated J-domain protein co-chaperone (Hsc20). Hsc20 stimulates Hsp70's ATPase activity, thus stabilizing the critical Isu-Hsp70 interaction. While most eukaryotes utilize a multifunctional mitochondrial (mt)Hsp70, yeast employ another Hsp70 (Ssq1), a product of mtHsp70 gene duplication. Ssq1 became specialized in FeS biogenesis, recapitulating the process in bacteria, where specialized Hsp70 HscA cooperates exclusively with an ortholog of Hsc20. While it is well established that Ssq1 and HscA converged functionally for FeS transfer, whether these two Hsp70s possess similar biochemical properties was not known. Here, we show that overall HscA and Ssq1 biochemical properties are very similar, despite subtle differences being apparent - the ATPase activity of HscA is stimulated to a somewhat higher levels by Isu and Hsc20, while Ssq1 has a higher affinity for Isu and for Hsc20. HscA/Ssq1 are a unique example of biochemical convergence of distantly related Hsp70s, with practical implications, crossover experimental results can be combined, facilitating understanding of the FeS transfer process.

RevDate: 2020-05-12

Seebacher F (2020)

Is Endothermy an Evolutionary By-Product?.

Trends in ecology & evolution, 35(6):503-511.

Endothermy alters the energetic relationships between organisms and their environment and thereby influences fundamental niches. Endothermy is closely tied to energy metabolism. Regulation of energy balance is indispensable for all life and regulatory pathways increase in complexity from bacteria to vertebrates. Increasing complexity of metabolic networks also increase the probability for endothermic phenotypes to appear. Adaptive arguments are problematic epistemologically because the regulatory mechanisms enabling endothermy have not evolved for the 'purpose' of endothermy and the utility of current traits is likely to have changed over evolutionary time. It is most parsimonious to view endothermy as the evolutionary by-product of energy balance regulation rather than as an adaptation and interpret its evolution in the context of metabolic networks.

RevDate: 2020-05-12

Puertas M, M Gonzalez-Sanchez (2020)


Genome [Epub ahead of print].

We review the insertion of mitochondrial DNA (mtDNA) fragments into nuclear DNA (NUMTS) as a general and ongoing process that has occurred many times during genome evolution. Fragments of mtDNA are generated during the lifetime of organisms in both somatic and germinal cells, by the production of reactive oxygen species in the mitochondria The fragments are inserted into the nucleus during the double strand breaks repair via the non-homologous end joining machinery, followed by genomic instability, giving rise to the high variability observed in NUMT patterns among species, populations or genotypes. Some de novo produced mtDNA insertions show harmful effects, being involved in human diseases, carcinogenesis and ageing. NUMT generation is a non-stop process overpassing the Mendelian transmission. This parasitic property ensures their survival even against their harmful effects. The accumulation of mtDNA fragments mainly at pericentromeric and subtelomeric regions is important to understand the transmission and integration of NUMTs into the genomes. The possible effect on of female meiotic drive for mtDNA insertions at centromeres remains to be studied. In spite of the harmful feature of NUMTs, they are important in cell evolution representing a major source of genomic variation.

RevDate: 2020-05-12

De Chiara M, Friedrich A, Barré B, et al (2020)

Discordant evolution of mitochondrial and nuclear yeast genomes at population level.

BMC biology, 18(1):49 pii:10.1186/s12915-020-00786-4.

BACKGROUND: Mitochondria are essential organelles partially regulated by their own genomes. The mitochondrial genome maintenance and inheritance differ from the nuclear genome, potentially uncoupling their evolutionary trajectories. Here, we analysed mitochondrial sequences obtained from the 1011 Saccharomyces cerevisiae strain collection and identified pronounced differences with their nuclear genome counterparts.

RESULTS: In contrast with pre-whole genome duplication fungal species, S. cerevisiae mitochondrial genomes show higher genetic diversity compared to the nuclear genomes. Strikingly, mitochondrial genomes appear to be highly admixed, resulting in a complex interconnected phylogeny with a weak grouping of isolates, whereas interspecies introgressions are very rare. Complete genome assemblies revealed that structural rearrangements are nearly absent with rare inversions detected. We tracked intron variation in COX1 and COB to infer gain and loss events throughout the species evolutionary history. Mitochondrial genome copy number is connected with the nuclear genome and linearly scale up with ploidy. We observed rare cases of naturally occurring mitochondrial DNA loss, petite, with a subset of them that do not suffer the expected growth defect in fermentable rich media.

CONCLUSIONS: Overall, our results illustrate how differences in the biology of two genomes coexisting in the same cells can lead to discordant evolutionary histories.

RevDate: 2020-05-12
CmpDate: 2020-05-12

Hamamcı B, Açıkgöz G, Kılıç E, et al (2019)

Biochemical Analysis of Germinal Membrane and Cyst Fluid by Raman Spectroscopy in Echinococcosis.

Turkiye parazitolojii dergisi, 43(4):175-181.

Objective: Hydatidosis is a zoonotic parasitic infection caused by the larval stage of Echinococcus granulosus. The aim of this study was to investigate the biochemical structures of germinal membrane and cyst fluids obtained from patients with liver involvement during surgery, by Raman spectroscopy at the molecular level.

Methods: Molecular characterization of germinal membrane and cyst fluid according to mitochondrial gene region was determined and phylogenetic analysis was performed. Raman spectroscopy was used in samples and spectral bands between 300 and 1800 cm-1 were examined.

Results: As a result of PCR, approximately 400 bp DNA band was obtained from germinal membranes and cyst fluids gathered from patients. Peaks were observed at 780, 880, 970, 1151, 1200, 1270 cm-1 for germinal membrane and at 780 and 1200 cm-1 for cyst fluid. The highest spectral bands were obtained at 1333-1335 cm-1 and were determined to be modes indicating the CH3CH2 collagen and polynucleotide chain.

Conclusion: In the identification of microorganisms and biochemical analysis of biological tissues; different diagnostic methods such as molecular, serological and conventional methods are used. In addition to these methods, Raman spectroscopy has been shown in studies to be a fast, non-destructive and noninvasive method. Therefore, it is thought to be an alternative method for analyzing the basic biochemical components of microorganisms at molecular level.

RevDate: 2020-05-11

Meduri GU, GP Chrousos (2020)

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections.

Frontiers in endocrinology, 11:161.

In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis.

RevDate: 2020-05-11
CmpDate: 2020-05-11

Chen J, Gong Y, Zheng H, et al (2019)

SpBcl2 promotes WSSV infection by suppressing apoptotic activity of hemocytes in mud crab, Scylla paramamosain.

Developmental and comparative immunology, 100:103421.

White spot syndrome virus (WSSV) is one of the most virulent and widespread pathogens that infect almost all marine crustaceans and therefore cause huge economic losses in aquaculture. The Bcl2 protein plays a key role in the mitochondrial apoptosis pathway, which is a crucial immune response in invertebrates. However, the role of Bcl2 in apoptosis and immunoregulation in mud crab, Scylla paramamosain, is poorly understood. Here, the Bcl2 homolog (SpBcl2) in S. paramamosain was cloned and its role in WSSV infection explored. The expression of SpBcl2 increased at both the transcriptional level and post-transcriptional level after WSSV infection, while the hemocytes apoptosis decreased significantly. Furthermore, there was increase in the level of cytochrome c coupled with an upregulation in the expression of SpBcl2. These results indicated that SpBcl2 suppressed apoptosis by preventing the release of cytochrome c from mitochondria, thereby promoting WSSV replication in mud crab. The findings here therefore provide novel insight into the immune response of mud crabs to WSSV infection.

RevDate: 2020-05-11
CmpDate: 2020-05-11

Gobert A, Bruggeman M, P Giegé (2019)

Involvement of PIN-like domain nucleases in tRNA processing and translation regulation.

IUBMB life, 71(8):1117-1125.

Transfer RNAs require essential maturation steps to become functional. Among them, RNase P removes 5' leader sequences of pre-tRNAs. Although RNase P was long thought to occur universally as ribonucleoproteins, different types of protein-only RNase P enzymes were discovered in both eukaryotes and prokaryotes. Interestingly, all these enzymes belong to the super-group of PilT N-terminal-like nucleases (PIN)-like ribonucleases. This wide family of enzymes can be subdivided into major subgroups. Here, we review recent studies at both functional and mechanistic levels on three PIN-like ribonucleases groups containing enzymes connected to tRNA maturation and/or translation regulation. The evolutive distribution of these proteins containing PIN-like domains as well as their organization and fusion with various functional domains is discussed and put in perspective with the diversity of functions they acquired during evolution, for the maturation and homeostasis of tRNA and a wider array of RNA substrates. © 2019 IUBMB Life, 2019 © 2019 IUBMB Life, 71(8):1117-1125, 2019.

RevDate: 2020-05-10

Gangloff EJ, Schwartz TS, Klabacka R, et al (2020)

Mitochondria as central characters in a complex narrative: Linking genomics, energetics, and pace-of-life in natural populations of garter snakes.

Experimental gerontology pii:S0531-5565(20)30315-6 [Epub ahead of print].

As a pacesetter for physiological processes, variation in metabolic rate can determine the shape of energetic trade-offs and thereby drive variation in life-history traits. In turn, such variation in metabolic performance and life-histories can have profound consequences for lifespan and lifetime fitness. Thus, the extent to which metabolic rate variation is due to phenotypic plasticity or fixed genetic differences among individuals or populations is likely to be shaped by natural selection. Here, we first present a generalized framework describing the central role of mitochondria in processes linking environmental, genomic, physiological, and aging variation. We then present a test of these relationships in an exemplary system: populations of garter snakes (Thamnophis elegans) exhibiting contrasting life-history strategies - fast-growing, early-reproducing, and fast-aging (FA) versus slow-growing, late-reproducing, and slow-aging (SA). Previous work has characterized divergences in mitochondrial function, reactive oxygen species processing, and whole-organism metabolic rate between these divergent life-history ecotypes. Here, we report new data on cellular respiration and mitochondrial genomics and synthesize these results with previous work. We test hypotheses about the causes and implications of mitochondrial genome variation within this generalized framework. First, we demonstrate that snakes of the FA ecotype increase cellular metabolic rate across their lifespan, while the opposite pattern holds for SA snakes, implying that reduced energetic throughput is associated with a longer life. Second, we show that variants in mitochondrial genomes are segregating across the landscape in a manner suggesting selection on the physiological consequences of this variation in habitats varying in temperature, food availability, and rates of predation. Third, we demonstrate functional variation in whole-organism metabolic rate related to these mitochondrial genome sequence variants. With this synthesis of numerous datasets, we are able to further characterize how variation across levels of biological organization interact within this generalized framework and how this has resulted in the emergence of distinct life-history ecotypes that vary in their rates of aging and lifespan.

RevDate: 2020-05-07
CmpDate: 2020-05-07

Dubin A, Jørgensen TE, Jakt LM, et al (2019)

The mitochondrial transcriptome of the anglerfish Lophius piscatorius.

BMC research notes, 12(1):800.

OBJECTIVE: Analyze key features of the anglerfish Lophius piscatorius mitochondrial transcriptome based on high-throughput total RNA sequencing.

RESULTS: We determined the complete mitochondrial DNA and corresponding transcriptome sequences of L. piscatorius. Key features include highly abundant mitochondrial ribosomal RNAs (10-100 times that of mRNAs), and that cytochrome oxidase mRNAs appeared > 5 times more abundant than both NADH dehydrogenase and ATPase mRNAs. Unusual for a vertebrate mitochondrial mRNA, the polyadenylated COI mRNA was found to harbor a 75 nucleotide 3' untranslated region. The mitochondrial genome expressed several non-canonical genes, including the long noncoding RNAs lncCR-H, lncCR-L and lncCOI. Whereas lncCR-H and lncCR-L mapped to opposite strands in a non-overlapping organization within the control region, lncCOI appeared novel among vertebrates. We found lncCOI to be a highly abundant mitochondrial RNA in antisense to the COI mRNA. Finally, we present the coding potential of a humanin-like peptide within the large subunit ribosomal RNA.

RevDate: 2020-05-07
CmpDate: 2020-05-07

Wu B, W Hao (2019)

Mitochondrial-encoded endonucleases drive recombination of protein-coding genes in yeast.

Environmental microbiology, 21(11):4233-4240.

Mitochondrial recombination in yeast is well recognized, yet the underlying genetic mechanisms are not well understood. Recent progress has suggested that mobile introns in mitochondrial genomes (mitogenomes) can facilitate the recombination of their corresponding intron-containing genes through a mechanism known as intron homing. As many mitochondrial genes lack introns, there is a critical need to determine the extent of recombination and underlying mechanism of intron-lacking genes. This study leverages yeast mitogenomes to address these questions. In Saccharomyces cerevisiae, the 3'-end sequences of at least three intron-lacking mitochondrial genes exhibit elevated nucleotide diversity and recombination hotspots. Each of these 3'-end sequences is immediately adjacent to or even fused as overlapping genes with a stand-alone endonuclease. Our findings suggest that SAEs are responsible for recombination and elevated diversity of adjacent intron-lacking genes. SAEs were also evident to drive recombination of intron-lacking genes in Lachancea kluyveri, a yeast species that diverged from S. cerevisiae more than 100 million years ago. These results suggest SAEs as a common driver in recombination of intron-lacking genes during mitogenome evolution. We postulate that the linkage between intron-lacking gene and its adjacent endonuclease gene is the result of co-evolution.

RevDate: 2020-05-06

Scorziello A, Borzacchiello D, Sisalli MJ, et al (2020)

Mitochondrial Homeostasis and Signaling in Parkinson's Disease.

Frontiers in aging neuroscience, 12:100.

The loss of dopaminergic (DA) neurons in the substantia nigra leads to a progressive, long-term decline of movement and other non-motor deficits. The symptoms of Parkinson's disease (PD) often appear later in the course of the disease, when most of the functional dopaminergic neurons have been lost. The late onset of the disease, the severity of the illness, and its impact on the global health system demand earlier diagnosis and better targeted therapy. PD etiology and pathogenesis are largely unknown. There are mutations in genes that have been linked to PD and, from these complex phenotypes, mitochondrial dysfunction emerged as central in the pathogenesis and evolution of PD. In fact, several PD-associated genes negatively impact on mitochondria physiology, supporting the notion that dysregulation of mitochondrial signaling and homeostasis is pathogenically relevant. Derangement of mitochondrial homeostatic controls can lead to oxidative stress and neuronal cell death. Restoring deranged signaling cascades to and from mitochondria in PD neurons may then represent a viable opportunity to reset energy metabolism and delay the death of dopaminergic neurons. Here, we will highlight the relevance of dysfunctional mitochondrial homeostasis and signaling in PD, the molecular mechanisms involved, and potential therapeutic approaches to restore mitochondrial activities in damaged neurons.

RevDate: 2020-05-06

Chen H, Shi Z, Guo J, et al (2020)

The human mitochondrial 12S rRNA m4C methyltransferase METTL15 is required for mitochondrial function.

The Journal of biological chemistry pii:RA119.012127 [Epub ahead of print].

Mitochondrial DNA (mtDNA) gene expression is coordinately regulated both pre- and post-transcriptionally, and its perturbation can lead to human pathologies. Mitochondrial ribosomal RNAs (mt-rRNAs) undergo a series of nucleotide modifications after release from polycistronic mitochondrial RNA (mtRNA) precursors, which is essential for mitochondrial ribosomal biogenesis. Cytosine N4-methylation (m4C) at position 839 (m4C839) of the 12S small subunit (SSU) mt-rRNA was identified decades ago; however, its biogenesis and function have not been elucidated in detail. Here, using several approaches, including immunofluorescence, RNA immunoprecipitation and methylation assays, and bisulfite mapping, we demonstrate that human methyltransferase-like 15 (METTL15), encoded by a nuclear gene, is responsible for 12S mt-rRNA methylation at m4C839 both in vivo and in vitro We tracked the evolutionary history of RNA m4C methyltransferases and identified a difference in substrate preference between METTL15 and its bacterial ortholog rsmH. Additionally, unlike the very modest impact of a loss of m4C methylation in bacterial SSU rRNA on the ribosome, we found that METTL15 depletion results in impaired translation of mitochondrial protein-coding mRNAs and decreases mitochondrial respiration capacity. Our findings reveal that human METTL15 is required for mitochondrial function, delineate the evolution of methyltransferase substrate specificities and modification patterns in rRNA, and highlight a differential impact of m4C methylation on prokaryotic ribosomes and eukaryotic mitochondrial ribosomes.

RevDate: 2020-05-06
CmpDate: 2020-05-06

De AK, Muthiyan R, Ponraj P, et al (2019)

Mitogenome analysis of Indian isolate of Rhipicephalus microplus clade A sensu (): A first report from Maritime South-East Asia.

Mitochondrion, 49:135-148.

This communication reports a comprehensive profile of mitogenome analysis of Rhipicephalus microplus, isolated and identified from Andaman and Nicobar islands, a part of Maritime South East Asia. Complete mitogenome of Indian isolate of R. microplus (MK234703) was 14,903 bp. Mitochondrial (mt.) genome had 13 protein coding genes (PCGs), 22 tRNAs, two ribosomal subunits and two control regions. All PCGs were located on the H-strand except nad1, nad5, nad4 and nad4L. All start codons were ATN codon and abbreviated stop codons were seen in cox-2-3, nad-5 and cytb. A purine rich tick-box motif has been identified. A tandem repeat unit (TTTATT), described as a region alike to nad1 was identified in 130 bp insertion in between nad1 and tRNA-Glu and in nad1 sequence. Presence of two control regions (CRs) proved that, two CRs have evolved in concert rather than independently. Strong biasness towards A and T in Indian isolate of R. microplus is a typical feature for most of the arthropods. Subtracted values of dn and ds suggested that, there was least effect of nt. sequence of cox1 gene when Indian isolate was compared with other isolates of Rhipicephalus. On the basis of phylogenetic analysis, species of the genus Rhipicephalus could be clustered in three groups; ticks of the genera belonging to sub-family Rhipicephalinae could be grouped in a single cluster. Finally, cox1 sequence of MK234703 indicated that the isolate belonged to clade A sensu Burger et al., 2014 which has not been reported earlier from India.

RevDate: 2020-05-06
CmpDate: 2020-05-06

Dobler R, Dowling DK, Morrow EH, et al (2019)

Reply: Mitochondrial replacement and its effects on human health: accounting for non-independence of data in meta-analyses.

Human reproduction update, 25(3):393-394.

RevDate: 2020-05-05
CmpDate: 2020-04-20

Woodyard ET, Stilwell JM, Camus AC, et al (2019)

Molecular and Histopathological Data on Levisunguis subaequalis Curran, Overstreet, Collins & Benz, 2014 (Pentastomida: Eupentastomida: Porocephalida: Porocephaloidea: Sebekidae: Sebekinae) from Gambusia affinis in Alabama, USA.

The Journal of parasitology, 105(6):827-839.

Levisunguis subaequalis Curran, Overstreet, Collins & Benz, 2014 , was recently described from the lungs of the definitive hosts, softshell turtles, Apalone ferox (Schneider, 1783), and Apalone spinifera aspera (Agassiz, 1857) as well as the viscera of an intermediate host, the western mosquitofish, Gambusia affinis (Baird and Girard, 1853). However, the original account lacked molecular data. Furthermore, histological examination of infected host tissues in the original account of L. subaequalis did not reveal any pathological changes in the intermediate host. The present work provides a robust morphological description of the nymph and novel molecular data from the 18S and 28S ribosomal gene regions and the cytochrome c oxidase subunit 1 (COI) mitochondrial gene. Phylogenetic analyses using Bayesian inference and maximum likelihood analysis with concatenated sequence data from these 3 regions, as well as each region individually, placed the turtle pentastomid L. subaequalis as a sister clade to the crocodilian pentastomids of the genus Sebekia Sambon, 1922. While only concatenated phylogenetic analyses agreed with the currently accepted classification of the Eupentastomida and phylogenetic signal assessment indicated that the concatenated data set yielded the most phylogenetic signal, data from more taxa are still needed for robust phylogenetic inferences to be made. The intensity of infection ranged from 2 to 171 nymphs per fish, compared with the highest previously reported intensity of 6. These high-intensity infections with L. subaequalis were characterized by the nymphs occupying 5-50% of the coelomic cavity of G. affinis. However, despite this heavy parasite infection, fish exhibited minimal pathology. Observed pathology was characterized by compression or effacement of organs adjacent to the nymphs, particularly liver, swim bladder, and intestines, as well as the formation of granulomas around shed pentastomid cuticles. Nonetheless, the morphological and molecular data provided in the present work will bolster future efforts to identify this pentastomid in other hosts where pathology may be present in addition to aiding in the advancement of the field of molecular pentastomid systematics.

RevDate: 2020-05-05
CmpDate: 2020-05-05

Gerosa C, Fanni D, Congiu T, et al (2019)

Liver pathology in Wilson's disease: From copper overload to cirrhosis.

Journal of inorganic biochemistry, 193:106-111.

Wilson's disease (WD) is a genetic metabolic disease strictly associated with liver cirrhosis. In this review, the genetic bases of the disease are discussed, with emphasis on the role of ATP7B (the Wilson disease protein) dysfunction as a determinant factor of systemic copper overload. Regarding the different multiple mutations described in WD patients, the peculiarity of Sardinian population is highlighted, Sardinians carrying a rare deletion in the promoter (5' UTR) of the WD gene. The role of epigenetic changes in the clinical presentation and evolution of liver disease in WD patients is also discussed, nutrition probably representing a relevantly risk factor in WD patients. The role of transmission electron microscopy in the diagnosis of WD-related liver disease is underlined. Mitochondrial changes, increased peroxisomes fat droplets, lipolysosomes and intranuclear glycogen inclusions are reported as the most frequent ultrastructural changes in the liver of WD carriers. The role of histochemical stains for copper is analyzed, and the Timm's method is suggested as the most sensitive one for revealing hepatic copper overload in all stage of WD. The marked variability of the histological liver changes occurring in WD is underlined simple steatosis may represent the only pathological changes, frequently associated with glycogenated nuclei. Mallory-Denk bodies lipogranulomas alcoholic and non-alcoholic fatty liver disease ending with bridging fibrosis and cirrhosis. Finally, the reversal of fibrosis as a possible therapeutic objective in WD is discussed.

RevDate: 2020-05-04

Pfannschmidt T, Terry MJ, Van Aken O, et al (2020)

Retrograde signals from endosymbiotic organelles: a common control principle in eukaryotic cells.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 375(1801):20190396.

Endosymbiotic organelles of eukaryotic cells, the plastids, including chloroplasts and mitochondria, are highly integrated into cellular signalling networks. In both heterotrophic and autotrophic organisms, plastids and/or mitochondria require extensive organelle-to-nucleus communication in order to establish a coordinated expression of their own genomes with the nuclear genome, which encodes the majority of the components of these organelles. This goal is achieved by the use of a variety of signals that inform the cell nucleus about the number and developmental status of the organelles and their reaction to changing external environments. Such signals have been identified in both photosynthetic and non-photosynthetic eukaryotes (known as retrograde signalling and retrograde response, respectively) and, therefore, appear to be universal mechanisms acting in eukaryotes of all kingdoms. In particular, chloroplasts and mitochondria both harbour crucial redox reactions that are the basis of eukaryotic life and are, therefore, especially susceptible to stress from the environment, which they signal to the rest of the cell. These signals are crucial for cell survival, lifespan and environmental adjustment, and regulate quality control and targeted degradation of dysfunctional organelles, metabolic adjustments, and developmental signalling, as well as induction of apoptosis. The functional similarities between retrograde signalling pathways in autotrophic and non-autotrophic organisms are striking, suggesting the existence of common principles in signalling mechanisms or similarities in their evolution. Here, we provide a survey for the newcomers to this field of research and discuss the importance of retrograde signalling in the context of eukaryotic evolution. Furthermore, we discuss commonalities and differences in retrograde signalling mechanisms and propose retrograde signalling as a general signalling mechanism in eukaryotic cells that will be also of interest for the specialist. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.

RevDate: 2020-05-04
CmpDate: 2020-05-04

Vesteg M, Hadariová L, Horváth A, et al (2019)

Comparative molecular cell biology of phototrophic euglenids and parasitic trypanosomatids sheds light on the ancestor of Euglenozoa.

Biological reviews of the Cambridge Philosophical Society, 94(5):1701-1721.

Parasitic trypanosomatids and phototrophic euglenids are among the most extensively studied euglenozoans. The phototrophic euglenid lineage arose relatively recently through secondary endosymbiosis between a phagotrophic euglenid and a prasinophyte green alga that evolved into the euglenid secondary chloroplast. The parasitic trypanosomatids (i.e. Trypanosoma spp. and Leishmania spp.) and the freshwater phototrophic euglenids (i.e. Euglena gracilis) are the most evolutionary distant lineages in the Euglenozoa phylogenetic tree. The molecular and cell biological traits they share can thus be considered as ancestral traits originating in the common euglenozoan ancestor. These euglenozoan ancestral traits include common mitochondrial presequence motifs, respiratory chain complexes containing various unique subunits, a unique ATP synthase structure, the absence of mitochondria-encoded transfer RNAs (tRNAs), a nucleus with a centrally positioned nucleolus, closed mitosis without dissolution of the nuclear membrane and nucleoli, a nuclear genome containing the unusual 'J' base (β-D-glucosyl-hydroxymethyluracil), processing of nucleus-encoded precursor messenger RNAs (pre-mRNAs) via spliced-leader RNA (SL-RNA) trans-splicing, post-transcriptional gene silencing by the RNA interference (RNAi) pathway and the absence of transcriptional regulation of nuclear gene expression. Mitochondrial uridine insertion/deletion RNA editing directed by guide RNAs (gRNAs) evolved in the ancestor of the kinetoplastid lineage. The evolutionary origin of other molecular features known to be present only in either kinetoplastids (i.e. polycistronic transcripts, compaction of nuclear genomes) or euglenids (i.e. monocistronic transcripts, huge genomes, many nuclear cis-spliced introns, polyproteins) is unclear.

RevDate: 2020-04-30
CmpDate: 2020-04-30

Peyrégne S, Slon V, Mafessoni F, et al (2019)

Nuclear DNA from two early Neandertals reveals 80,000 years of genetic continuity in Europe.

Science advances, 5(6):eaaw5873.

Little is known about the population history of Neandertals over the hundreds of thousands of years of their existence. We retrieved nuclear genomic sequences from two Neandertals, one from Hohlenstein-Stadel Cave in Germany and the other from Scladina Cave in Belgium, who lived around 120,000 years ago. Despite the deeply divergent mitochondrial lineage present in the former individual, both Neandertals are genetically closer to later Neandertals from Europe than to a roughly contemporaneous individual from Siberia. That the Hohlenstein-Stadel and Scladina individuals lived around the time of their most recent common ancestor with later Neandertals suggests that all later Neandertals trace at least part of their ancestry back to these early European Neandertals.

RevDate: 2020-04-29

Bateman A (2020)

Division of labour in a matrix, rather than phagocytosis or endosymbiosis, as a route for the origin of eukaryotic cells.

Biology direct, 15(1):8 pii:10.1186/s13062-020-00260-9.

Two apparently irreconcilable models dominate research into the origin of eukaryotes. In one model, amitochondrial proto-eukaryotes emerged autogenously from the last universal common ancestor of all cells. Proto-eukaryotes subsequently acquired mitochondrial progenitors by the phagocytic capture of bacteria. In the second model, two prokaryotes, probably an archaeon and a bacterial cell, engaged in prokaryotic endosymbiosis, with the species resident within the host becoming the mitochondrial progenitor. Both models have limitations. A search was therefore undertaken for alternative routes towards the origin of eukaryotic cells. The question was addressed by considering classes of potential pathways from prokaryotic to eukaryotic cells based on considerations of cellular topology. Among the solutions identified, one, called here the "third-space model", has not been widely explored. A version is presented in which an extracellular space (the third-space), serves as a proxy cytoplasm for mixed populations of archaea and bacteria to "merge" as a transitionary complex without obligatory endosymbiosis or phagocytosis and to form a precursor cell. Incipient nuclei and mitochondria diverge by division of labour. The third-space model can accommodate the reorganization of prokaryote-like genomes to a more eukaryote-like genome structure. Nuclei with multiple chromosomes and mitosis emerge as a natural feature of the model. The model is compatible with the loss of archaeal lipid biochemistry while retaining archaeal genes and provides a route for the development of membranous organelles such as the Golgi apparatus and endoplasmic reticulum. Advantages, limitations and variations of the "third-space" models are discussed. REVIEWERS: This article was reviewed by Damien Devos, Buzz Baum and Michael Gray.

RevDate: 2020-04-28

López-García P, D Moreira (2020)

The Syntrophy hypothesis for the origin of eukaryotes revisited.

Nature microbiology, 5(5):655-667.

The discovery of Asgard archaea, phylogenetically closer to eukaryotes than other archaea, together with improved knowledge of microbial ecology, impose new constraints on emerging models for the origin of the eukaryotic cell (eukaryogenesis). Long-held views are metamorphosing in favour of symbiogenetic models based on metabolic interactions between archaea and bacteria. These include the classical Searcy's and Hydrogen hypothesis, and the more recent Reverse Flow and Entangle-Engulf-Endogenize models. Two decades ago, we put forward the Syntrophy hypothesis for the origin of eukaryotes based on a tripartite metabolic symbiosis involving a methanogenic archaeon (future nucleus), a fermentative myxobacterial-like deltaproteobacterium (future eukaryotic cytoplasm) and a metabolically versatile methanotrophic alphaproteobacterium (future mitochondrion). A refined version later proposed the evolution of the endomembrane and nuclear membrane system by invagination of the deltaproteobacterial membrane. Here, we adapt the Syntrophy hypothesis to contemporary knowledge, shifting from the original hydrogen and methane-transfer-based symbiosis (HM Syntrophy) to a tripartite hydrogen and sulfur-transfer-based model (HS Syntrophy). We propose a sensible ecological scenario for eukaryogenesis in which eukaryotes originated in early Proterozoic microbial mats from the endosymbiosis of a hydrogen-producing Asgard archaeon within a complex sulfate-reducing deltaproteobacterium. Mitochondria evolved from versatile, facultatively aerobic, sulfide-oxidizing and, potentially, anoxygenic photosynthesizing alphaproteobacterial endosymbionts that recycled sulfur in the consortium. The HS Syntrophy hypothesis accounts for (endo)membrane, nucleus and metabolic evolution in a realistic ecological context. We compare and contrast the HS Syntrophy hypothesis to other models of eukaryogenesis, notably in terms of the mode and tempo of eukaryotic trait evolution, and discuss several model predictions and how these can be tested.

RevDate: 2020-04-27

Pearson SA, Wachnowsky C, JA Cowan (2020)

Defining the mechanism of the mitochondrial Atm1p [2Fe-2S] cluster exporter.

Metallomics : integrated biometal science [Epub ahead of print].

Iron-sulfur cluster proteins play key roles in a multitude of physiological processes; including gene expression, nitrogen and oxygen sensing, electron transfer, and DNA repair. Biosynthesis of iron-sulfur clusters occurs in mitochondria on iron-sulfur cluster scaffold proteins in the form of [2Fe-2S] cores that are then transferred to apo targets within metabolic or respiratory pathways. The mechanism by which cytosolic Fe-S cluster proteins mature to their holo forms remains controversial. The mitochondrial inner membrane protein Atm1p can transport glutathione-coordinated iron-sulfur clusters, which may connect the mitochondrial and cytosolic iron-sulfur cluster assembly systems. Herein we describe experiments on the yeast Atm1p/ABCB7 exporter that provide additional support for a glutathione-complexed cluster as the natural physiological substrate and a reflection of the endosymbiotic model of mitochondrial evolution. These studies provide insight on the mechanism of cluster transport and the molecular basis of human disease conditions related to ABCB7. Recruitment of MgATP following cluster binding promotes a structural transition from closed to open conformations that is mediated by coupling helices, with MgATP hydrolysis facilitating the return to the closed state.

RevDate: 2020-04-27
CmpDate: 2020-04-27

Mishmar D (2020)

mtDNA in the crossroads of evolution and disease.

Nature reviews. Molecular cell biology, 21(4):181.

RevDate: 2020-04-27
CmpDate: 2020-04-27

Cronshaw M, Parker S, P Arany (2019)

Feeling the Heat: Evolutionary and Microbial Basis for the Analgesic Mechanisms of Photobiomodulation Therapy.

Photobiomodulation, photomedicine, and laser surgery, 37(9):517-526.

Background: The clinical therapeutic benefits of Photobiomodulation (PBM) therapy have been well established in many clinical scenarios. However, we are far from having developed a complete understanding of the underlying mechanisms of photon-biological tissue interactions. Concurrent to ongoing PBM studies, there are several parallel fields with evidences from cell and tissue physiology such as evolutionary biology, photobiology, and microbiology among others. Objective: This review is focused on extrapolating evidences from an expanded range of studies that may contribute to a better understanding of PBM mechanisms especially focusing on analgesia. Further, the choice of a PBM device source and relevant dosimetry with regards to specific mechanisms are discussed to enable broader clinical use of PBM therapies. Materials and methods: This discussion article is referenced from an expanded range of peer reviewed publications, including literature associated with evolutionary biology, microbiology, oncology, and photo-optical imaging technology, amongst others. Results and discussion: Materials drawn from many disparate disciplines is described. By inference from the current evidence base, a novel theory is offered to partially explain the cellular basis of PBM-induced analgesia. It is proposed that this may involve the activity of a class of transmembrane proteins known as uncoupling proteins. Furthermore, it is proposed that this may activate the heat stress protein response and that intracellur microthermal inclines may be of significance in PBM analgesia. It is suggested that the PBM dose response as a simple binary model of PBM effects as represented by the Arndt-Schulz law is clinically less useful than a multiphasic biological response. Finally, comments are made concerning the nature of photon to tissue interaction that can have significance in regard to the effective choice and delivery of dose to clinical target. Conclusions: It is suggested that a re-evaluation of phototransduction pathways may lead to an improvement in outcome in phototheraphy. An enhanced knowledge of safe parameters and a better knowledge of the mechanics of action at target level will permit more reliable and predictable clinical gain and assist the acceptance of PBM therapy within the wider medical community.

RevDate: 2020-04-25

Waltz F, Corre N, Hashem Y, et al (2020)

Specificities of the plant mitochondrial translation apparatus.

Mitochondrion pii:S1567-7249(20)30013-1 [Epub ahead of print].

Mitochondria are endosymbiotic organelles responsible for energy production in most eukaryotic cells. They host a genome and a fully functional gene expression machinery. In plants this machinery involves hundreds of pentatricopeptide repeat (PPR) proteins. Translation, the final step of mitochondrial gene expression is performed by mitochondrial ribosomes (mitoribosomes). The nature of these molecular machines remained elusive for a very long time. Because of their bacterial origin, it was expected that mitoribosomes would closely resemble bacterial ribosomes. However, recent advances in cryo-electron microscopy have revealed the extraordinary diversity of mitoribosome structure and composition. The plant mitoribosome was characterized for Arabidopsis. In plants, in contrast to other species such as mammals and kinetoplastids where rRNA has been largely reduced, the mitoribosome could be described as a protein/RNA-augmented bacterial ribosome. It has an oversized small subunit formed by expanded ribosomal RNAs and additional protein components when compared to bacterial ribosomes. The same holds true for the large subunit. The small subunit is characterized by a new elongated domain on the head. Among its additional proteins, several PPR proteins are core mitoribosome proteins. They mainly act at the structural level to stabilize and maintain the plant-specific ribosomal RNA expansions but could also be involved in translation initiation. Recent advances in plant mitoribosome composition and structure, its specialization for membrane protein synthesis, translation initiation, the regulation and dynamics of mitochondrial translation are reviewed here and put in perspective with the diversity of mitochondrial translation processes in the green lineage and in the wider context of eukaryote evolution.

RevDate: 2020-04-25

Kaufer A, Stark D, J Ellis (2020)

A review of the systematics, species identification and diagnostics of the Trypanosomatidae using the maxicircle kinetoplast DNA: from past to present.

International journal for parasitology pii:S0020-7519(20)30090-4 [Epub ahead of print].

The Trypanosomatid family are a diverse and widespread group of protozoan parasites that belong to the higher order class Kinetoplastida. Containing predominantly monoxenous species (i.e. those having only a single host) that are confined to invertebrate hosts, this class is primarily known for its pathogenic dixenous species (i.e. those that have two hosts), serving as the aetiological agents of the important neglected tropical diseases (NTDs) including leishmaniasis, American trypanosomiasis (Chagas disease) and human African trypanosomiasis. Over the past few decades, a multitude of studies have investigated the diversity, classification and evolutionary history of the trypanosomatid family using different approaches and molecular targets. The mitochondrial-like DNA of the trypanosomatid parasites, also known as the kinetoplast, has emerged as a unique taxonomic and diagnostic target for exploring the evolution of this diverse group of parasitic eukaryotes. This review discusses recent advancements and important developments that have made a significant impact in the field of trypanosomatid systematics and diagnostics in recent years.

RevDate: 2020-04-24

Rotterová J, Salomaki E, Pánek T, et al (2020)

Genomics of New Ciliate Lineages Provides Insight into the Evolution of Obligate Anaerobiosis.

Current biology : CB pii:S0960-9822(20)30434-6 [Epub ahead of print].

Oxygen plays a crucial role in energetic metabolism of most eukaryotes. Yet adaptations to low-oxygen concentrations leading to anaerobiosis have independently arisen in many eukaryotic lineages, resulting in a broad spectrum of reduced and modified mitochondrion-related organelles (MROs). In this study, we present the discovery of two new class-level lineages of free-living marine anaerobic ciliates, Muranotrichea, cl. nov. and Parablepharismea, cl. nov., that, together with the class Armophorea, form a major clade of obligate anaerobes (APM ciliates) within the Spirotrichea, Armophorea, and Litostomatea (SAL) group. To deepen our understanding of the evolution of anaerobiosis in ciliates, we predicted the mitochondrial metabolism of cultured representatives from all three classes in the APM clade by using transcriptomic and metagenomic data and performed phylogenomic analyses to assess their evolutionary relationships. The predicted mitochondrial metabolism of representatives from the APM ciliates reveals functional adaptations of metabolic pathways that were present in their last common ancestor and likely led to the successful colonization and diversification of the group in various anoxic environments. Furthermore, we discuss the possible relationship of Parablepharismea to the uncultured deep-sea class Cariacotrichea on the basis of single-gene analyses. Like most anaerobic ciliates, all studied species of the APM clade host symbionts, which we propose to be a significant accelerating factor in the transitions to an obligately anaerobic lifestyle. Our results provide an insight into the evolutionary mechanisms of early transitions to anaerobiosis and shed light on fine-scale adaptations in MROs over a relatively short evolutionary time frame.

RevDate: 2020-04-23

Yang F, Jin H, Wang XQ, et al (2020)

Genomic Analysis of Mic1 Reveals a Novel Freshwater Long-Tailed Cyanophage.

Frontiers in microbiology, 11:484.

Lake Chaohu, one of the five largest freshwater lakes in China, has been suffering from severe cyanobacterial blooms in the summer for many years. Cyanophages, the viruses that specifically infect cyanobacteria, play a key role in modulating cyanobacterial population, and thus regulate the emergence and decline of cyanobacterial blooms. Here we report a long-tailed cyanophage isolated from Lake Chaohu, termed Mic1, which specifically infects the cyanobacterium Microcystis aeruginosa. Mic1 has an icosahedral head of 88 nm in diameter and a long flexible tail of 400 nm. It possesses a circular genome of 92,627 bp, which contains 98 putative open reading frames. Genome sequence analysis enabled us to define a novel terminase large subunit that consists of two types of intein, indicating that the genome packaging of Mic1 is under fine control via posttranslational maturation of the terminase. Moreover, phylogenetic analysis suggested Mic1 and mitochondria share a common evolutionary origin of DNA polymerase γ gene. All together, these findings provided a start-point for investigating the co-evolution of cyanophages and its cyanobacterial hosts.

RevDate: 2020-04-21

Almeida C, MD Amaral (2020)

A central role of the endoplasmic reticulum in the cell emerges from its functional contact sites with multiple organelles.

Cellular and molecular life sciences : CMLS pii:10.1007/s00018-020-03523-w [Epub ahead of print].

Early eukaryotic cells emerged from the compartmentalization of metabolic processes into specific organelles through the development of an endomembrane system (ES), a precursor of the endoplasmic reticulum (ER), which was essential for their survival. Recently, substantial evidence emerged on how organelles communicate among themselves and with the plasma membrane (PM) through contact sites (CSs). From these studies, the ER-the largest single structure in eukaryotic cells-emerges as a central player communicating with all organelles to coordinate cell functions and respond to external stimuli to maintain cellular homeostasis. Herein we review the functional insights into the ER-CSs with other organelles in a physiological perspective. We hypothesize that, in addition to the primitive role by the ES in the appearance of proto-eukaryotes, its successor-the ER-emerges as the key coordinator of inter-organelle/PM communication. The ER thus appears to be the 'maestro' driving eukaryotic cell evolution by incorporating new functions/organelles, while remaining the real coordinator overarching cellular functions and orchestrating them with the external milieu.

RevDate: 2020-04-20

Lee EH, Baek SY, Park JY, et al (2020)

Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo/Yap signalling pathway.

Pharmaceutical biology, 58(1):333-341.

Context: Emodin is a compound in Rheum undulatum Linne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects.Objective: Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism.Materials and methods: We used the hepatocyte stimulated by arachidonic acid (AA) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 ∼ 30 μM) for 1 h before AA + iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP.Results:In vitro, emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 μM (EC50 > 3 μM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 μM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway. In vivo, the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage.Conclusion: Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway.

RevDate: 2020-04-20
CmpDate: 2020-04-20

Arnedo M, Latorre-Pellicer A, Lucia-Campos C, et al (2019)

More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones.

International journal of molecular sciences, 20(24):.

There are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low. Another isoform is encoded by the same gene for the mitochondrial HMG-CoA lyase (HMGCL), but it is located in peroxisomes. The last HMG-CoA lyase to be described is encoded by a different gene, HMGCLL1, and is located in the cytosolic side of the endoplasmic reticulum membrane. Some activity assays and tissue distribution of this enzyme have shown the brain and lung as key tissues for studying its function. Although the roles of the peroxisomal and cytosolic HMG-CoA lyases remain unknown, recent studies highlight the role of ketone bodies in metabolic remodeling, homeostasis, and signaling, providing new insights into the molecular and cellular function of these enzymes.

RevDate: 2020-04-20
CmpDate: 2020-04-20

Phillips CB, Tsai CW, MF Tsai (2019)

The conserved aspartate ring of MCU mediates MICU1 binding and regulation in the mitochondrial calcium uniporter complex.

eLife, 8:.

The mitochondrial calcium uniporter is a Ca2+ channel that regulates intracellular Ca2+ signaling, oxidative phosphorylation, and apoptosis. It contains the pore-forming MCU protein, which possesses a DIME sequence thought to form a Ca2+ selectivity filter, and also regulatory EMRE, MICU1, and MICU2 subunits. To properly carry out physiological functions, the uniporter must stay closed in resting conditions, becoming open only when stimulated by intracellular Ca2+ signals. This Ca2+-dependent activation, known to be mediated by MICU subunits, is not well understood. Here, we demonstrate that the DIME-aspartate mediates a Ca2+-modulated electrostatic interaction with MICU1, forming an MICU1 contact interface with a nearby Ser residue at the cytoplasmic entrance of the MCU pore. A mutagenesis screen of MICU1 identifies two highly-conserved Arg residues that might contact the DIME-Asp. Perturbing MCU-MICU1 interactions elicits unregulated, constitutive Ca2+ flux into mitochondria. These results indicate that MICU1 confers Ca2+-dependent gating of the uniporter by blocking/unblocking MCU.

RevDate: 2020-04-16

Waters ER, E Vierling (2020)

Plant small heat shock proteins - evolutionary and functional diversity.

The New phytologist [Epub ahead of print].

Small heat shock proteins (sHSPs) are an ubiquitous protein family found in archaea, bacteria and eukaryotes. In plants, as in other organisms, sHSPs are upregulated by stress and are proposed to act as molecular chaperones to protect other proteins from stress-induced damage. sHSPs share an 'α-crystallin domain' with a β-sandwich structure and a diverse N-terminal domain. Although sHSPs are 12-25 kDa polypeptides, most assemble into oligomers with ≥ 12 subunits. Plant sHSPs are particularly diverse and numerous; some species have as many as 40 sHSPs. In angiosperms this diversity comprises ≥ 11 sHSP classes encoding proteins targeted to the cytosol, nucleus, endoplasmic reticulum, chloroplasts, mitochondria and peroxisomes. The sHSPs underwent a lineage-specific gene expansion, diversifying early in land plant evolution, potentially in response to stress in the terrestrial environment, and expanded again in seed plants and again in angiosperms. Understanding the structure and evolution of plant sHSPs has progressed, and a model for their chaperone activity has been proposed. However, how the chaperone model applies to diverse sHSPs and what processes sHSPs protect are far from understood. As more plant genomes and transcriptomes become available, it will be possible to explore theories of the evolutionary pressures driving sHSP diversification.

RevDate: 2020-04-15
CmpDate: 2020-04-15

Zhang Y, Feng S, Fekrat L, et al (2019)

The first two complete mitochondrial genome of Dacus bivittatus and Dacus ciliatus (Diptera: Tephritidae) by next-generation sequencing and implications for the higher phylogeny of Tephritidae.

International journal of biological macromolecules, 140:469-476.

Dacus bivittatus and Dacus ciliatus are destructive pests of Cucurbitaceae crops including cucumber, zucchini and melons. Recent molecular phylogenetic studies conflicted with morphological taxonomy regarding relationships between Bactrocera, Dacus and Zeugodacus. In this study, we sequenced the complete mitochondrial genomes of the above species which are representatives of two subgenera of Dacus (Dacus and Didacus) not previously sequenced and reconstructed the phylogeny of Tephritidae. The mitochondrial genomes of D. bivittatus and D. ciliatus were 15,833 bp and 15,808 bp in length, respectively. The 37 genes, including 13 protein-coding genes (PCGs), 2 rRNA genes and 22 tRNA genes, with a long non-coding region (A + T-rich control region) were in the same arrangement as the ancestral insect mitochondrial genome. Phylogenetic analysis showed that Dacus has a closer relationship of Zeugodacus rather than Bactrocera. Our phylogenetic results further support the recent proposals that Zeugodacus should be considered as a genus not a subgenus of Bactrocera. Whole mitochondrial genomes of D. bivittatus and D. ciliatus could be useful in further studies for species diagnosis, evolution and phylogeny research within Tephritidae.

RevDate: 2020-04-13
CmpDate: 2020-04-13

Derouiche L, Irzagh A, Rahmouni R, et al (2020)

Deep mitochondrial DNA phylogeographic divergence in the threatened aoudad Ammotragus lervia (Bovidae, Caprini).

Gene, 739:144510.

The aoudad or Barbary sheep (Ammotragus lervia) is a threatened ungulate emblematic of North Africa, whose population structure and subspecific taxonomy have not been examined genetically. This knowledge is essential and urgently needed to inform ongoing conservation and management efforts. We analysed the mitochondrial cytochrome b gene and four nuclear genes (casein kappa, spectrin beta nonerythrocytic 1, thyroglobulin, thyrotropin subunit beta) for the first phylogeographic survey of the aoudad, and uncovered a deep Mediterranean-Saharan mitochondrial split separating two highly distinct evolutionary lineages. Their level of divergence is greater than or comparable to those observed between several pairs of congeneric species of different caprine genera. The split was estimated to have occurred in the Early Pleistocene, about 1.3 million years ago. None of the four nuclear genes surveyed, chosen because they have been used in phylogeographic and species-level phylogenetic studies of bovids, allowed us to detect, likely due to their slow evolutionary rate, the substantial and geographically coherent subdivision revealed by mitochondrial DNA. This study is evidence and testament to the ability of mitochondrial DNA, probably unrivalled by any other single-locus marker, as an exploratory tool for investigating population genealogy and history and identifying potential evolutionarily significant units for conservation in animals.

RevDate: 2020-04-13
CmpDate: 2020-04-13

Barili V, Fisicaro P, Montanini B, et al (2020)

Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection.

Nature communications, 11(1):604.

Hepatitis C virus infection (HCV) represents a unique model to characterize, from early to late stages of infection, the T cell differentiation process leading to exhaustion of human CD8+ T cells. Here we show that in early HCV infection, exhaustion-committed virus-specific CD8+ T cells display a marked upregulation of transcription associated with impaired glycolytic and mitochondrial functions, that are linked to enhanced ataxia-telangiectasia mutated (ATM) and p53 signaling. After evolution to chronic infection, exhaustion of HCV-specific T cell responses is instead characterized by a broad gene downregulation associated with a wide metabolic and anti-viral function impairment, which can be rescued by histone methyltransferase inhibitors. These results have implications not only for treatment of HCV-positive patients not responding to last-generation antivirals, but also for other chronic pathologies associated with T cell dysfunction, including cancer.

RevDate: 2020-04-13
CmpDate: 2020-04-13

Laurimäe T, Kinkar L, Romig T, et al (2019)

Analysis of nad2 and nad5 enables reliable identification of genotypes G6 and G7 within the species complex Echinococcus granulosus sensu lato.

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 74:103941.

The larval stages of tapeworms in the species complex Echinococcus granulosus sensu lato cause a zoonotic disease known as cystic echinococcosis (CE). Within this species complex, genotypes G6 and G7 are among the most common genotypes associated with human CE cases worldwide. However, our understanding of ecology, biology and epidemiology of G6 and G7 is still limited. An essential first step towards this goal is correct genotype identification, but distinguishing genotypes G6 and G7 has been challenging. A recent analysis based on complete mitogenome data revealed that the conventional sequencing of the cox1 (366 bp) gene fragment mistakenly classified a subset of G7 samples as G6. On the other hand, sequencing complete mitogenomes is not practical if only genotype or haplogroup identification is needed. Therefore, a simpler and less costly method is required to distinguish genotypes G6 and G7. We compared 93 complete mitogenomes of G6 and G7 from a wide geographical range and demonstrate that a combination of nad2 (714 bp) and nad5 (680 bp) gene fragments would be the best option to distinguish G6 and G7. Moreover, this method allows assignment of G7 samples into haplogroups G7a and G7b. However, due to very high genetic variability of G6 and G7, we suggest to construct a phylogenetic network based on the nad2 and nad5 sequences in order to be absolutely sure in genotype assignment. For this we provide a reference dataset of 93 concatenated nad2 and nad5 sequences (1394 bp in total) containing representatives of G6 and G7 (and haplogroups G7a and G7b), which can be used for the reconstruction of phylogenetic networks.

RevDate: 2020-04-13
CmpDate: 2020-04-13

Chen N, Wang P, Li C, et al (2018)

A Single Nucleotide Mutation of the IspE Gene Participating in the MEP Pathway for Isoprenoid Biosynthesis Causes a Green-Revertible Yellow Leaf Phenotype in Rice.

Plant & cell physiology, 59(9):1905-1917.

Plant isoprenoids are dependent on two independent pathways, the cytosolic mevalonate (MVA) pathway and the plastidic methylerythritol phosphate (MEP) pathway. IspE is one of seven known enzymes in the MEP pathway. Currently, no IspE gene has been identified in rice. In addition, no virescent mutants have been reported to result from a gene mutation affecting the MEP pathway. In this study, we isolated a green-revertible yellow leaf mutant gry340 in rice. The mutant exhibited a reduced level of photosynthetic pigments, and an arrested development of chloroplasts and mitochondria in its yellow leaves. Map-based cloning revealed a missense mutation in OsIspE (LOC_Os01g58790) in gry340 mutant plants. OsIspE is constitutively expressed in all tissues, and its encoded protein is targeted to the chloroplast. Further, the mutant phenotype of gry340 was rescued by introduction of the wild-type gene. Therefore, we have successfully identified an IspE gene in monocotyledons via map-based cloning, and confirmed that the green-revertible yellow leaf phenotype of gry340 does result from a single nucleotide mutation in the IspE gene. In addition, the ispE ispF double mutant displayed an etiolation lethal phenotype, indicating that the isoprenoid precursors from the cytosol cannot efficiently compensate for the deficiency of the MEP pathway in rice chloroplasts. Furthermore, real-time quantitative reverse transcription-PCR suggested that this functional defect in OsIspE affected the expression of not only other MEP pathway genes but also that of MVA pathway genes, photosynthetic genes and mitochondrial genes.

RevDate: 2020-04-10
CmpDate: 2020-04-10

Sato C, Sasaki M, Nabeta H, et al (2019)

A Philophthalmid Eyefluke from a Human in Japan.

The Journal of parasitology, 105(4):619-623.

Philophthalmid eyeflukes are cosmopolitan parasites of birds and occasionally of mammals, including humans. A gravid adult of Philophthalmus sp. was found from the bulbar conjunctiva of a 64-yr-old woman in Japan, who was diagnosed with acute conjunctivitis. The parasite was morphologically most similar to Philophthalmus hegeneri, but distinctive in lacking an esophagus and in having clearly lobed testes. The DNA sequence analysis of genes for nuclear 28S ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 supported the identification at generic level. The morphological and molecular analyses strongly suggest that the eyefluke from a human in Japan should be treated as an undescribed species of Philophthalmus. The occurrence of human philophthalmosis is very rare. As far as we know, a total of 11 human cases have been reported worldwide to date.

RevDate: 2020-04-09
CmpDate: 2020-04-09

Owuor SA, Mamati EG, RW Kasili (2019)

Origin, Genetic Diversity, and Population Structure of Rabbits (Oryctolagus cuniculus) in Kenya.

BioMed research international, 2019:7056940.

To evaluate the origin, genetic diversity, and population structure of domesticated rabbits in Kenya, a 263-base pair region of mtDNA D-loop region of 111 rabbits sampled from Kakamega, Vihiga, and Bungoma counties in the western region, Laikipia and Nyandarua counties in the central region, and Kitui, Machakos, and Makueni in the eastern region of the country were analyzed. The average haplotype (0.40702) and nucleotide (0.01494) diversities observed were low, indicating low genetic diversity of domesticated rabbits in Kenya. This study resolved 5 unique haplotypes in the mtDNA D-loop region. A population genetic structure distinguishing Europe grouping and domesticated rabbits in Kenya was obtained on incorporating 32 known haplotypes. Domesticated rabbits in Kenya clustered together with rabbits from other geographic regions, suggesting common origin. The results suggested that the Kenyan domesticated rabbits may have originated from Europe. Integration of exotic breeds into breeding programmes could have contributed to the low genetic diversity. These results provide useful information for breeding and conservation decisions by the relevant stakeholders in the agriculture industry in Kenya.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Ceríaco LMP, Agarwal I, Marques MP, et al (2020)

A review of the genus Hemidactylus Goldfuss, 1820 (Squamata: Gekkonidae) from Angola, with the description of two new species.

Zootaxa, 4746(1):zootaxa.4746.1.1 pii:zootaxa.4746.1.1.

The genus Hemidactylus in Angola is represented by six species, all of them part of taxonomically and nomenclaturally challenging species complexes. We present a detailed taxonomic revision of the group in the region and describe two new species, Hemidactylus nzingae sp. nov. and Hemidactylus paivae sp. nov., both occuring in and potentially endemic to the highlands of Angola. Phylogenetic analysis using a combination of mitochondrial (ND2) and nuclear (MXRA5, PDC, RAG1) markers, as well as morphological and scalation data support the recognition of the new species. In addition, data support the revalidation of Hemidactylus bayonii Bocage, 1893, and Hemidactylus benguellensis Bocage, 1893. We also provide a redefinition of Hemidactylus longicephalus Bocage, 1873 with which we synonymize Hemidactylus mabouia molleri Bedriaga, 1892, from São Tomé in the Gulf of Guinea. Given that the type material of H. bayonii, H. benguellensis, H. longicephalus and H. mabouia molleri have all been lost or destroyed, we designate neotypes for all of these nomina for purposes of nomenclatural stability. The description of the new species and the revision and revalidation of the Angolan species already described contributes to a better understanding of the taxonomy and biogeography of West and Central African Hemidactylus, as well as to the general biogeographic and evolutionary patterns of Angolan fauna. A key to the Angolan species is also presented.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Abou-Shaara HF (2019)

Utilizing bioinformatics to detect genetic similarities between African honey bee subspecies.

Journal of genetics, 98:.

Various honey bees, especially subspecies Apis mellifera, occur in Africa and are distribute across the continent. The genetic relationships and identical genetic characteristics between honey bee subspecies in Africa (African bee subspecies) have not been widely investigated using sequence analysis. On the other hand, bioinformatics are developed rapidly and have diverse applications. It is anticipated that bioinformatics can show the genetic relationships and similarities among subspecies. These points have high importance, especially subspecies with identical genetic characteristics can be infected with the same group of pathogens, which have implications on honey bee health. In this study, the mitochondrial DNA sequences of four African subspecies and Africanized bees were subjected to the analyses of base composition, phylogeny, shared gene clusters, enzymatic digestion, and open reading frames. High identical base composition was detected in the studied subspecies, and high identical results from all tests were found between A. m. scutellata and A. m. capensis followed by A. m. intermissa and A. m. monticola. The least genetic relationships were found between A. m. lamarckii and the other subspecies. This study presents insights into the genetic aspects of African bee subspecies and highlights similarity and dissimilarity aspects. Also, Africanized honey bees derived from A. m. scutellata showed high genetic similarities to other African bees, especially A. m. capensis. Additionally, specific primers to identify these subspecies were designed and tested.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Kumar De A, Ponraj P, Malakar D, et al (2019)

Complete mitogenome sequencing of Andaman buffalo: an endangered germplasm of Andaman and Nicobar Islands, India.

Journal of genetics, 98:.

Andaman buffalo is an indigenous buffalo of Andaman and Nicobar Islands, India. Over the last decade, it has witnessed a rapid decline in population, necessitating its immediate characterization and conservation. The present study reports the complete mitogenome profile of Andaman buffalo which is 16,359 bp in length and comprised of 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNAs and two ribosomal RNAs. In addition, one A + T rich region (D-loop) was also present. A biasness towards A and T base was observed in all the genes. All the PCGs except ND6 were present on heavy strand. Start codons for all the 13 PCGs were ATN codon and abbreviated/truncated stop codons were observed in ND1, ND2, COX3, ND3 and ND4. The phylogenetic analysis revealed that the Andaman buffalo is closely related to buffalo from India and China. The results from this study will help in sketching the conservation plan of the threatened breed.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Achatz TJ, Dmytrieva I, Kuzmin Y, et al (2019)

Phylogenetic Position of Codonocephalus Diesing, 1850 (Digenea, Diplostomoidea), an Unusual Diplostomid with Progenetic Metacercariae.

The Journal of parasitology, 105(5):821-826.

Codonocephalus is a monotypic genus of diplostomid digeneans and is the only genus in the sub-family Codonocephalinae. The type-species Codonocephalus urniger has an unusual progenetic metacercaria that uses frogs as intermediate hosts and can use snakes as paratenic hosts. Adult C. urniger parasitize ardeid wading birds in the Palearctic. Despite the broad distribution of Codonocephalus, no DNA sequence data are currently available for the genus. In this study, we generated sequence data for nuclear ribosomal and mitochondrial DNA from progenetic metacercaria of the type-species C. urniger from marsh frog, Pelophylax ridibundus, collected in Ukraine. We used partial sequences of the nuclear ribosomal 28S gene to examine for the first time the phylogenetic position of Codonocephalus among the Diplostomoidea.

RevDate: 2020-04-08
CmpDate: 2020-04-06

de Oliveira Simões R, Fraga-Neto S, Vilar EM, et al (2019)

A New Species of Bidigiticauda (Nematoda: Strongylida) from the Bat Artibeus Planirostris (Chiroptera: Phyllostomidae) in the Atlantic Forest and a Molecular Phylogeny of the Molineid Bat Parasites.

The Journal of parasitology, 105(5):783-792.

The nematode genus Bidigiticauda has 2 species (Bidigiticauda vivipara and Bidigiticauda embryophilum), which are parasites of bats from the Neotropical region. The present paper describes a new species of Bidigiticauda from a male Artibeus planirostris specimen collected in the Pratigi Environmental Protection Area in Bahia state, Brazil. The new species, Bidigiticauda serrafreirei n. sp., differs from B. embryophilum by having longer spicules, rays 5 and 6 arising from a common trunk and bifurcating in its first third, rays 3 and 4 emerging slightly separated from each other, and dorsal rays reaching the margin of the caudal bursa. The new species also differs from B. vivipara by the dorsal ray bifurcating at the extremity of the trunk. A molecular phylogenetic analysis was conducted to determine the evolutionary affinities of Bidigiticauda serrafreirei n. sp. within the Strongylida, which identified a clade that grouped Bidigiticauda with the other members of the Anoplostrongylinae. However, the molineid subfamilies did not group together, indicating that the family Molineidae is polyphyletic. Further analyses, which include additional taxa and genetic markers, should elucidate the complex relationships within the Molineidae, in particular its subfamilies and the evolution of the traits that define these groups.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Velázquez-Urrieta Y, Oceguera-Figueroa A, V León-Règagnon (2019)

Two New Species of Haematoloechus (Digenea: Plagiorchidae) Parasitizing Rana brownorum (Amphibia: Ranidae) from Southeast Mexico.

The Journal of parasitology, 105(5):724-732.

In an ongoing investigation on the helminths of amphibians in southeastern Mexico, specimens of 2 undescribed species of Haematoloechus were collected from Rana brownorum. Haematoloechus ceciliae n. sp. is morphologically most similar to Haematoloechus meridionalis, but differs in the shape of the oral sucker, in the nature of the acetabulum, and in the distribution of the glandular cells in the pharyngeal region; Haematoloechus celestunensis n. sp. closely resembles Haematoloechus floedae, but differs in the form and size of the testes and measurements of acetabulum. COI and 28S DNA sequences of both new species show high divergence compared to other species of the genus. In the phylogenetic trees, H. ceciliae appears most closely related to Haematoloechus danbrooksi and H. celestunensis to Haematoloechus veracruzanus.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Achatz TJ, Curran SS, Patitucci KF, et al (2019)

Phylogenetic Affinities of Uvulifer Spp. (Digenea: Diplostomidae) in the Americas with Description of Two New Species from Peruvian Amazon.

The Journal of parasitology, 105(5):704-717.

Uvulifer Yamaguti, 1934, is a genus of diplostomoidean digeneans that parasitizes kingfishers worldwide. Species have a Neascus-type metacercaria that encysts in or on fish intermediate hosts, often causing black spot disease. Only 3 prior studies published DNA sequence data for Uvulifer species with only 1 including a single named species (Uvulifer spinatus López-Jiménez, Pérez-Ponce de León, & García-Varela, 2018). Herein we describe 2 new species of Uvulifer from the green-and-rufous kingfisher, Chloroceryle inda (Linnaeus), collected in Peru (Uvulifer batesi n. sp. and Uvulifer pequenae n. sp.). Both new species are readily differentiated from their New World congeners by a combination of morphological characters including distribution of vitelline follicles and prosoma:opisthosoma length ratios. In addition, we used newly generated nuclear 28S rRNA and mitochondrial COI gene sequence data to differentiate among species and examine phylogenetic affinities of Uvulifer. This includes the 2 new species and Uvulifer ambloplitis (Hughes, 1927), as well as Uvulifer elongatus Dubois, 1988 , Uvulifer prosocotyle (Lutz, 1928), and Uvulifer weberi Dubois, 1985 , none of which have been part of prior molecular phylogenetic studies. Our data on Uvulifer revealed 0.1-2.2% interspecific divergence in 28S sequences and 9.3-15.3% in COI sequences. Our 28S phylogeny revealed at least 6 well-supported clades within the genus. In contrast, the branch topology in the COI phylogenetic tree was overall less supported, indicating that although COI sequences are a great tool for species differentiation, they should be used with caution for phylogenetic inference at higher taxonomic levels. Our 28S phylogeny did not reveal any clear patterns of host association between Uvulifer and particular species of kingfishers; however, it identified 2 well-supported clades uniting Uvulifer species from distant geographical locations and more than 1 biogeographic realm, indicating at least 2 independent dispersal events in the evolutionary history of the New World Uvulifer. Our results clearly demonstrate that the diversity of Uvulifer in the New World has been underestimated.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Cui R, Medeiros T, Willemsen D, et al (2019)

Relaxed Selection Limits Lifespan by Increasing Mutation Load.

Cell, 178(2):385-399.e20.

To uncover the selective forces shaping life-history trait evolution across species, we investigate the genomic basis underlying adaptations to seasonal habitat desiccation in African killifishes, identifying the genetic variants associated with positive and relaxed purifying selection in 45 killifish species and 231 wild individuals distributed throughout sub-Saharan Africa. In annual species, genetic drift led to the expansion of nuclear and mitochondrial genomes and caused the accumulation of deleterious genetic variants in key life-history modulating genes such as mtor, insr, ampk, foxo3, and polg. Relaxation of purifying selection is also significantly associated with mitochondrial function and aging in human populations. We find that relaxation of purifying selection prominently shapes genomes and is a prime candidate force molding the evolution of lifespan and the distribution of genetic variants associated with late-onset diseases in different species. VIDEO ABSTRACT.

RevDate: 2020-04-06

Waltz F, Soufari H, Bochler A, et al (2020)

Cryo-EM structure of the RNA-rich plant mitochondrial ribosome.

Nature plants pii:10.1038/s41477-020-0631-5 [Epub ahead of print].

The vast majority of eukaryotic cells contain mitochondria, essential powerhouses and metabolic hubs1. These organelles have a bacterial origin and were acquired during an early endosymbiosis event2. Mitochondria possess specialized gene expression systems composed of various molecular machines, including the mitochondrial ribosomes (mitoribosomes). Mitoribosomes are in charge of translating the few essential mRNAs still encoded by mitochondrial genomes3. While chloroplast ribosomes strongly resemble those of bacteria4,5, mitoribosomes have diverged significantly during evolution and present strikingly different structures across eukaryotic species6-10. In contrast to animals and trypanosomatids, plant mitoribosomes have unusually expanded ribosomal RNAs and have conserved the short 5S rRNA, which is usually missing in mitoribosomes11. We have previously characterized the composition of the plant mitoribosome6, revealing a dozen plant-specific proteins in addition to the common conserved mitoribosomal proteins. In spite of the tremendous recent advances in the field, plant mitoribosomes remained elusive to high-resolution structural investigations and the plant-specific ribosomal features of unknown structures. Here, we present a cryo-electron microscopy study of the plant 78S mitoribosome from cauliflower at near-atomic resolution. We show that most of the plant-specific ribosomal proteins are pentatricopeptide repeat proteins (PPRs) that deeply interact with the plant-specific rRNA expansion segments. These additional rRNA segments and proteins reshape the overall structure of the plant mitochondrial ribosome, and we discuss their involvement in the membrane association and mRNA recruitment prior to translation initiation. Finally, our structure unveils an rRNA-constructive phase of mitoribosome evolution across eukaryotes.

RevDate: 2020-04-04

Rank NE, Mardulyn P, Heidl SJ, et al (2020)

Mitonuclear mismatch alters performance and reproductive success in naturally-introgressed populations of a montane leaf beetle.

Evolution; international journal of organic evolution [Epub ahead of print].

Coordination between nuclear and mitochondrial genomes is critical to metabolic processes underlying animals' ability to adapt to local environments, yet consequences of mitonuclear interactions have rarely been investigated in populations where individuals with divergent mitochondrial and nuclear genomes naturally interbreed. Genetic variation in the leaf beetle Chrysomela aeneicollis was assessed along a latitudinal thermal gradient in California's Sierra Nevada. Variation at mitochondrial cytochrome oxidase II (COII) and the nuclear gene phosphoglucose isomerase (PGI) shows concordance and was significantly greater along a 65 km transect than 10 other loci. STRUCTURE analyses using neutral loci identified a southern and northern subpopulation, which interbreed in the central drainage Bishop Creek. COII and PGI were used as indicators of mitochondrial and nuclear genetic variation in field and laboratory experiments conducted on beetles from this admixed population. Fecundity, larval development rate, running speed and male mating frequency were higher for beetles with geographically 'matched' than 'mismatched' mitonuclear genotypes. Effects of mitonuclear mismatch were largest for individuals with northern nuclear genotypes possessing southern mitochondria and were most pronounced after heat treatment or at high elevation. These findings suggest that mitonuclear incompatibility diminishes performance and reproductive success in nature, effects that could intensify at environmental extremes. This article is protected by copyright. All rights reserved.

RevDate: 2020-04-04

Guan X, Okazaki Y, Zhang R, et al (2020)

Dual-localized enzymatic components constitute the fatty acid synthase systems in mitochondria and plastids.

Plant physiology pii:pp.19.01564 [Epub ahead of print].

Plant fatty acid biosynthesis occurs in both plastids and mitochondria. Here, we report the identification and characterization of Arabidopsis (Arabidopsis thaliana) genes encoding three enzymes shared between the mitochondria- and plastid-localized Type II fatty acid synthase systems (mtFAS and ptFAS, respectively). Two of these enzymes, β-ketoacyl-acyl carrier protein (ACP) reductase (pt/mtKR) and enoyl-ACP reductase (pt/mtER) catalyze two of the reactions that constitute the core four-reaction cycle of the FAS system, which iteratively elongates the acyl-chain by two carbon atoms per cycle. The third enzyme, malonyl-CoA:ACP transacylase (pt/mtMCAT) catalyzes the reaction that loads the mtFAS system with substrate by malonylating the phosphopantetheinyl cofactor of ACP. Green fluorescent protein (GFP) fusion experiments revealed that the these enzymes localize to both chloroplasts and mitochondria. This localization was validated by characterization of mutant alleles, which were rescued by transgenes expressing enzyme variants that were retargeted only to plastids or only mitochondria. The singular retargeting of these proteins to plastids rescued the embryo-lethality associated with disruption of the essential ptFAS system, but these rescued plants displayed phenotypes typical of the lack of mtFAS function, including reduced lipoylation of the H subunit of the glycine decarboxylase complex, hyperaccumulation of glycine, and reduced growth. However, these latter traits were reversible in an elevated CO2 atmosphere, which suppresses mtFAS-associated photorespiration-dependent chemotypes. Sharing enzymatic components between mtFAS and ptFAS systems constrains the evolution of these non-redundant fatty acid biosynthetic machineries.

RevDate: 2020-04-04

Harada R, Hirakawa Y, Yabuki A, et al (2020)

Inventory and Evolution of Mitochondrion-localized Family A DNA Polymerases in Euglenozoa.

Pathogens (Basel, Switzerland), 9(4): pii:pathogens9040257.

The order Trypanosomatida has been well studied due to its pathogenicity and the unique biology of the mitochondrion. In Trypanosoma brucei, four DNA polymerases, namely PolIA, PolIB, PolIC, and PolID, related to bacterial DNA polymerase I (PolI), were shown to be localized in mitochondria experimentally. These mitochondrion-localized DNA polymerases are phylogenetically distinct from other family A DNA polymerases, such as bacterial PolI, DNA polymerase gamma (Polγ) in human and yeasts, "plant and protist organellar DNA polymerase (POP)" in diverse eukaryotes. However, the diversity of mitochondrion-localized DNA polymerases in Euglenozoa other than Trypanosomatida is poorly understood. In this study, we discovered putative mitochondrion-localized DNA polymerases in broad members of three major classes of Euglenozoa-Kinetoplastea, Diplonemea, and Euglenida-to explore the origin and evolution of trypanosomatid PolIA-D. We unveiled distinct inventories of mitochondrion-localized DNA polymerases in the three classes: (1) PolIA is ubiquitous across the three euglenozoan classes, (2) PolIB, C, and D are restricted in kinetoplastids, (3) new types of mitochondrion-localized DNA polymerases were identified in a prokinetoplastid and diplonemids, and (4) evolutionarily distinct types of POP were found in euglenids. We finally propose scenarios to explain the inventories of mitochondrion-localized DNA polymerases in Kinetoplastea, Diplonemea, and Euglenida.

RevDate: 2020-04-04

Hewitt SK, Duangrattanalert K, Burgis T, et al (2020)

Plasticity of Mitochondrial DNA Inheritance and its Impact on Nuclear Gene Transcription in Yeast Hybrids.

Microorganisms, 8(4): pii:microorganisms8040494.

Mitochondrial DNA (mtDNA) in yeast is biparentally inherited, but colonies rapidly lose one type of parental mtDNA, thus becoming homoplasmic. Therefore, hybrids between the yeast species possess two homologous nuclear genomes, but only one type of mitochondrial DNA. We hypothesise that the choice of mtDNA retention is influenced by its contribution to hybrid fitness in different environments, and the allelic expression of the two nuclear sub-genomes is affected by the presence of different mtDNAs in hybrids. Saccharomyces cerevisiae/S.uvarum hybrids preferentially retained S.uvarum mtDNA when formed on rich media at colder temperatures, while S. cerevisiae mtDNA was primarily retained on non-fermentable carbon source, at any temperature. Transcriptome data for hybrids harbouring different mtDNA showed a strong environmentally dependent allele preference, which was more important in respiratory conditions. Co-expression analysis for specific biological functions revealed a clear pattern of concerted allelic transcription within the same allele type, which supports the notion that the hybrid cell works preferentially with one set of parental alleles (or the other) for different cellular functions. Given that the type of mtDNA retained in hybrids affects both nuclear expression and fitness, it might play a role in driving hybrid genome evolution in terms of gene retention and loss.

RevDate: 2020-04-01

Khosravi S, ME Harner (2020)

The MICOS complex, a structural element of mitochondria with versatile functions.

Biological chemistry pii:/j/bchm.just-accepted/hsz-2020-0103/hsz-2020-0103.xml [Epub ahead of print].

Mitochondria perform a plethora of functions in various cells of different tissues. Their architecture differs remarkably, for instance in neurons versus steroidogenic cells. Furthermore, aberrant mitochondrial architecture results in mitochondrial dysfunction. This indicates strongly that mitochondrial architecture and function are intimately linked. Therefore, a deep knowledge about the determinants of mitochondrial architecture and their function on a molecular level is of utmost importance. In the past decades, various proteins and protein complexes essential for formation of mitochondrial architecture have been identified. Here we will review the current knowledge of the MICOS complex, one of the major structural elements of mitochondria. MICOS is a multi-subunit complex present in the inner mitochondrial membrane. Multiple interaction partners in the inner and outer mitochondrial membrane point to participation in a multitude of important processes, such as generation of mitochondrial architecture, lipid metabolism, and protein import into mitochondria. Since the MICOS complex is highly conserved in form and function throughout evolution, we will highlight the importance of MICOS for mammals. We will emphasize in particular the current knowledge of the association of MICOS with severe human diseases, including Charcot-Marie-Tooth disease type 2, Alzheimer's disease, Parkinson's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

RevDate: 2020-04-01
CmpDate: 2020-04-01

Barbosa AD, Austen J, Portas TJ, et al (2019)

Sequence analyses at mitochondrial and nuclear loci reveal a novel Theileria sp. and aid in the phylogenetic resolution of piroplasms from Australian marsupials and ticks.

PloS one, 14(12):e0225822.

The order Piroplasmida encompasses two main families: Babesiidae and Theileriidae, containing tick-borne pathogens of veterinary and medical importance worldwide. While only three genera (Babesia, Cytauxzoon and Theileria) comprising piroplasm parasites are currently recognised, phylogenetic studies at the 18S rRNA (18S) gene suggest that these organisms represent at least ten lineages, one of which comprises the relatively unique and highly diverse Theileria spp. from Australian marsupials and ticks. As an alternative to analysing 18S sequences alone, sequencing of mitochondrial genes has proven to be useful for the elucidation of evolutionary relationships amongst some groups of piroplasms. This research aimed to characterise piroplasms from Australian native mammals and ticks using multiple genetic markers (18S, cytochrome c, oxidase subunit III (cox3) and cytochrome B (cytB)) and microscopy. For this, nearly complete piroplasm-18S sequences were obtained from 32 animals belonging to six marsupial species: eastern bettong (Bettongia gaimardi), eastern quoll (Dasyurus viverrinus), eastern grey kangaroo (Macropus giganteus), swamp wallaby (Wallabia bicolor), quokka (Setonix brachyurus) and Gilbert's potoroo (Potorous gilbertii). The organisms detected represented eight novel Theileria genotypes, which formed five sub-clades within the main marsupial clade containing previously reported Australian marsupial and tick-derived Theileria spp. A selection of both novel and previously described Australian piroplasms at the 18S were also successfully characterised, for the first time, at the cox3 and cytB loci, and corroborated the position of Australian native theilerias in a separate, well-supported clade. Analyses of the cox3 and cytB genes also aided in the taxonomic resolution within the clade of Australian Piroplasmida. Importantly, microscopy and molecular analysis at multiple loci led to the discovery of a unique piroplasm species that clustered with the Australian marsupial theilerias, for which we propose the name Theileria lupei n. sp.

RevDate: 2020-03-31

Petersen G, Anderson B, Braun HP, et al (2020)

Mitochondria in parasitic plants.

Mitochondrion pii:S1567-7249(19)30341-1 [Epub ahead of print].

Plant mitochondrial genomes are renowned for their structural complexity, extreme variation in size and mutation rates, and ability to incorporate foreign DNA. Parasitic flowering plants are no exception, and the close association between parasite and host may even enhance the likelihood of horizontal gene transfer (HGT) between them. Recent studies on mistletoes (Viscum) have revealed that these parasites have lost an exceptional number of mitochondrial genes, including all complex I genes of the respiratory chain. At the same time, an altered respiratory pathway has been demonstrated. Here we review the current understanding of mitochondrial evolution in parasitic plants with a special emphasis on HGT to and from parasite mitochondrial genomes, as well as the uniquely altered mitochondria in Viscum and related plants.

RevDate: 2020-03-30
CmpDate: 2020-03-30

Muñoz-Gómez SA, Hess S, Burger G, et al (2019)

An updated phylogeny of the Alphaproteobacteria reveals that the parasitic Rickettsiales and Holosporales have independent origins.

eLife, 8:.

The Alphaproteobacteria is an extraordinarily diverse and ancient group of bacteria. Previous attempts to infer its deep phylogeny have been plagued with methodological artefacts. To overcome this, we analyzed a dataset of 200 single-copy and conserved genes and employed diverse strategies to reduce compositional artefacts. Such strategies include using novel dataset-specific profile mixture models and recoding schemes, and removing sites, genes and taxa that are compositionally biased. We show that the Rickettsiales and Holosporales (both groups of intracellular parasites of eukaryotes) are not sisters to each other, but instead, the Holosporales has a derived position within the Rhodospirillales. A synthesis of our results also leads to an updated proposal for the higher-level taxonomy of the Alphaproteobacteria. Our robust consensus phylogeny will serve as a framework for future studies that aim to place mitochondria, and novel environmental diversity, within the Alphaproteobacteria.

RevDate: 2020-03-30
CmpDate: 2020-03-30

Tsakiri EN, Gumeni S, Iliaki KK, et al (2019)

Hyperactivation of Nrf2 increases stress tolerance at the cost of aging acceleration due to metabolic deregulation.

Aging cell, 18(1):e12845.

Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti-stress responses; these adaptations were fundamental forces during evolution. Central to anti-stress responses are a number of short-lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in developmental lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics, the appearance of Diabetes Type 1 hallmarks and aging acceleration. Genetic or dietary suppression of Insulin/IGF-like signaling (IIS) titrated Nrf2 activity to lower levels, largely normalized metabolic pathways signaling, and extended flies' lifespan. Thus, prolonged stress signaling by otherwise cytoprotective short-lived stress sensors perturbs IIS resulting in re-allocation of resources from growth and longevity to somatic preservation and stress tolerance. These findings provide a reasonable explanation of why most (if not all) cytoprotective stress sensors are short-lived proteins, and it also explains the build-in negative feedback loops (shown here for Nrf2); the low basal levels of these proteins, and why their suppressors were favored by evolution.

RevDate: 2020-03-26

Yue J, Shen Y, Liang L, et al (2020)

Revealing mitochondrial microenvironmental evolution triggered by photodynamic therapy.

Analytical chemistry [Epub ahead of print].

Mitochondrion is one of the most important organelles and becomes a target in many cancer therapeutic strategies. Mitochondrial microenvironments in response to therapeutic methods are the key to understand therapeutic mechanisms. However, they are al-most rarely studied. Herein, the mitochondrial microenvironments, including mitochondrial membrane potential (MMP) and reac-tive oxygen species (ROS) after different photodynamic therapy (PDT) dosages, were monitored by fluorescent imaging and com-pared among three cell lines (HepG2, MCF-7, and LO2). Furthermore, the fluctuations of intra-mitochondrial pHs were revealed via a plasmonic mitochondrion-targeting surface-enhanced Raman scattering (SERS) pH nanosensor. Results indicate that the MMP decreases gradually with the ROS generation and the cancerous cells exhibit less responsive to excess ROS relative to nor-mal cells. On the other hand, the pH value in the mitochondria decreases initially and then increases when the amount of ROS increases. The LO2 cell is preliminarily evidenced to have a higher self-adjustment ability due to its better tolerance to differential intra/extra cellular pHs. This study may provide a basis for an in-depth understanding of the mechanisms of the mitochondrial tar-geting-based PDT therapeutic processes. It is also helpful for more accurate and useful diagnosis according to intra-mitochondrial microenvironments, and improvement on therapy efficiency of cancers.

RevDate: 2020-03-26
CmpDate: 2020-03-26

Ju Y, Liu H, He J, et al (2020)

Genetic diversity of Aoluguya Reindeer based on D-loop region of mtDNA and its conservation implications.

Gene, 733:144271.

Aoluguya Reindeer is the only reindeer population in China. In recent years, habitat loss and inbreeding have led to population decline, and population growth has been slow, maintaining a thousand or so. To better protect the Aoluguya Reindeer and improve its fecundity, we have introduced reindeer from Finland, crossbreeding help us to reach this goal. However, it is lacking in the study of genetic diversity of reindeer in China and Finland. Therefore, we used the partial sequences of the D-loop region of mitochondrial DNA to analyze the genetic diversity of Chinese reindeer (Aoluguya Reindeer) and the introduced Finnish reindeer, and identified twenty-six haplotypes, including nineteen in China, five in Finland, and two in Russia. There is no shared haplotype among them. The nucleotide diversity of Aoluguya Reindeer is 0.00752, which is significantly lower than that of reindeer in Finland and other countries. The haplotype and phylogenetic analysis show that reindeer from different geographical origins are not clustered completely according to geographical distribution. Aoluguya Reindeer populations and the introduced reindeer herds from Finland are all closely related to the reindeer from Russia. AMOVA analysis showed that there was significant differentiation between reindeer populations in China and Finland, and mismatch analysis showed that both populations had not experienced expansion. In this study, we identified the genetic diversity of Aoluguya Reindeer and the introduced reindeer, and provided a scientific basis for the conservation and breeding of Aoluguya Reindeer resources.

RevDate: 2020-03-26
CmpDate: 2020-03-26

Poljsak B, Kovac V, Dahmane R, et al (2019)

Cancer Etiology: A Metabolic Disease Originating from Life's Major Evolutionary Transition?.

Oxidative medicine and cellular longevity, 2019:7831952.

A clear understanding of the origins of cancer is the basis of successful strategies for effective cancer prevention and management. The origin of cancer at the molecular and cellular levels is not well understood. Is the primary cause of the origin of cancer the genomic instability or impaired energy metabolism? An attempt was made to present cancer etiology originating from life's major evolutionary transition. The first evolutionary transition went from simple to complex cells when eukaryotic cells with glycolytic energy production merged with the oxidative mitochondrion (The Endosymbiosis Theory first proposed by Lynn Margulis in the 1960s). The second transition went from single-celled to multicellular organisms once the cells obtained mitochondria, which enabled them to obtain a higher amount of energy. Evidence will be presented that these two transitions, as well as the decline of NAD+ and ATP levels, are the root of cancer diseases. Restoring redox homeostasis and reactivation of mitochondrial oxidative metabolism are important factors in cancer prevention.

RevDate: 2020-03-24

Orton LM, Fitzek E, Feng X, et al (2020)

Zygnema circumcarinatum UTEX 1559 chloroplast and mitochondrial genomes provide insight into land plant evolution.

Journal of experimental botany pii:5811179 [Epub ahead of print].

The complete chloroplast and mitochondrial genomes of Charophyta have shed new light on the land plant terrestrialization. Here, we reported the organellar genomes of the Zygnema circumcarinatum strain UTEX 1559, and a comparative genomics investigation of 33 plastomes and 18 mitogenomes of Chlorophyta, Charophyta (including UTEX 1559 and its conspecific relative SAG 698-1a), and Embryophyta. Gene presence/absence was determined across these plastomes and mitogenomes. A comparison between the plastomes of UTEX 1559 (157,548 bp) and SAG 698-1a (165,372 bp) revealed very similar gene contents, but substantial genome rearrangements. Surprisingly, the two plastomes share only 85.69% nucleotide sequence identity. The UTEX 1559 mitogenome size is 215,954 bp, the largest among all sequenced Charophyta. Interestingly, this large mitogenome contains a 50 kb region without homology to any other organellar genomes, which is flanked by two 86 bp direct repeats and contains 15 open reading frames (ORFs). These ORFs have significant homology to proteins from bacteria and plants with functions such as primase, RNA polymerase and DNA polymerase. We conclude that (i) the previously published SAG 698-1a plastome is likely from a different Zygnema species, and (ii) the 50 kb region in the UTEX 1559 mitogenome might be recently acquired as a mobile element.

RevDate: 2020-03-23

de Brito Monteiro L, Davanzo GG, de Aguiar CF, et al (2020)

M-CSF- and L929-derived macrophages present distinct metabolic profiles with similar inflammatory outcomes.

Immunobiology pii:S0171-2985(20)30068-1 [Epub ahead of print].

Macrophages are essential components of the immune system. Macrophages can be derived from the bone marrow of mice with either recombinant M-CSF or L929 supernatant. Recent literature considers recombinant M-CSF- and L929-derived macrophages as equals, even though L929-derived macrophages are exposed to other substances secreted in the L929 supernatant, and not only M-CSF. Thus, we decided to perform a comparative analysis of both inflammatory and metabolic profiles of macrophages differentiated under the aforementioned conditions, which is relevant for standardization and interpretation of in vitro studies. We observed that, when treated with LPS, L929macs secrete lower levels of proinflammatory cytokines (TNF-α, IL-6, IL12) and present higher glycolysis and oxygen consumption when compared with M-CSFmacs. L929macs also have increased mitochondrial mass, with higher percentage of dysfunctional mitochondria. This sort of information can help direct further studies towards a more specific approach for macrophage generation.

RevDate: 2020-03-22

Noguera R, Burgos-Panadero R, Lucantoni F, et al (2020)

[An integral view of cancer (III). Evaluation of new biomarkers and treatment strategies].

Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia, 53(2):88-99.

We propose a comprehensive approach to oncological disease, based on a systemic consideration of biology, health and disease. Our two previous review articles focused on tumour microenvironment and the discovery of new biomarkers; here we discuss the practical application of these principles to pathology, through the identification, evaluation and quantitative analysis of new prognostic and predictive factors (Immunoscore, TIME). We also consider the clinical use of promising, better tolerated treatments, such as immunotherapy. The integrative pathologist now has access to the latest improved oncology stratification tools designed to identify effective treatment strategies, based on the natural evolution of clinical and scientific knowledge that transcend the gene-centric theory of cancer.

RevDate: 2020-03-21

Buonvicino D, Ranieri G, Pratesi S, et al (2020)

Neuroprotection Induced by Dexpramipexole Delays Disease Progression in a Mouse Model of Progressive Multiple Sclerosis.

British journal of pharmacology [Epub ahead of print].

BACKGROUND AND PURPOSE: Drugs able to counteract progressive multiple sclerosis (PMS) represent a largely unmet therapeutic need. Even though the pathogenesis of disease evolution is still obscure, accumulating evidence indicates that mitochondrial dysfunction plays a causative role in neurodegeneration and axonopathy in PMS patients. Here, we investigated the effects of dexpramipexole, a compound with a good safety profile in humans and able to sustain mitochondria functioning and energy production, in a mouse model of PMS.

EXPERIMENTAL APPROACH: Female Non-obese diabetic (NOD) mice were immunized with MOG35-55 . Functional, immune and neuropathological parameters were analyzed during disease evolution in animals treated or not with dexpramipexole. The compound's effects on bioenergetics and neuroprotection were also evaluated in vitro.

KEY RESULTS: We found that oral treatment with dexpramipexole at a dose consistent with that well tolerated in humans delayed disability progression, extended survival, counteracted reduction of spinal cord mitochondrial DNA content and reduced spinal cord axonal loss of mice. Accordingly, the drug sustained in vitro bioenergetics of mouse optic nerve and dorsal root ganglia, and counteracted neurodegeneration of organotypic mouse cortical cultures exposed to the adenosine triphosphate (ATP)-depleting agents oligomycin or veratridine. Dexpramipexole, however, was unable to affect the adaptive and innate immune responses both in vivo and in vitro.

CONCLUSION AND IMPLICATION: The present findings corroborate the hypothesis that neuroprotective agents may be of relevance to counteract MS progression, and disclose the translational potential of dexpramipexole to treatment of PMS patients as a stand-alone or adjunctive therapy.

RevDate: 2020-03-18

Mbadinga Mbadinga DL, Li Q, Ranocha P, et al (2020)

Global analysis of non-animal peroxidases provides insights into the evolution of this gene family in the green lineage.

Journal of experimental botany pii:5809329 [Epub ahead of print].

The non-animal peroxidases belong to a superfamily of oxidoreductases that reduce the hydrogen peroxide and oxidize numerous substrates. Since their initial characterization in 1992, several advances have provided an understanding into the origin and evolution of this protein family. Here, we report the most comprehensive evolutionary analysis of non-animal peroxidases using integrated in silico and biochemical approaches. Thanks to the availability of numerous genomic sequences from more than 2500 species belonging to 14 kingdoms together with expert and comprehensive annotation of peroxidase sequences centralized in a dedicated database, we have deepened our understanding of the evolutionary process underlying non-animal peroxidases diversification through phylogenetic reconstructions. We analysed the distribution of all non-animal peroxidases in more than 200 eukaryotic organisms in silico. First, we show that the presence or absence of non-animal peroxidases correlate with the presence or absence of certain organelles or with specific biological processes. Scrutinizing in near 2000 organisms, we confirmed that ascorbate peroxidases (APx) and cytochromes c peroxidases (CcP) were detected respectively in chloroplast and mitochondria containing organisms. Plants, which contain both organelles, are an exception and contain only APxs without CcP. Class II peroxidases (CII Prx) only found in fungi with wood decay abilities and plant degradation and Class III peroxidases (CIII Prx) only detected in both streptophyte algae and land plants, have been subjected to large family expansion in the latter group. Moreover, we demonstrate that biochemical activities (APx, CcP and CIII Prx) assayed with protein extracts from 30 different eukaryotic organisms support the distribution of the sequences resulting from our in silico analysis. The biochemical results confirmed both the presence and classification of non-animal peroxidase encoding sequences.

RevDate: 2020-03-18

Warren JM, DB Sloan (2020)

Interchangeable parts: The evolutionarily dynamic tRNA population in plant mitochondria.

Mitochondrion pii:S1567-7249(19)30344-7 [Epub ahead of print].

Transfer RNAs (tRNAs) remain one of the very few classes of genes still encoded in the mitochondrial genome. These key components of the protein translation system must interact with a large enzymatic network of nuclear-encoded gene products to maintain mitochondrial function. Plants have an evolutionarily dynamic mitochondrial tRNA population, including ongoing tRNA gene loss and replacement by both horizontal gene transfer from diverse sources and import of nuclear-expressed tRNAs from the cytosol. Thus, plant mitochondria represent an excellent model for understanding how anciently divergent genes can act as "interchangeable parts" during the evolution of complex molecular systems. In particular, understanding the integration of the mitochondrial translation system with elements of the corresponding machinery used in cytosolic protein synthesis is a key area for eukaryotic cellular evolution. Here, we review the increasingly detailed phylogenetic data about the evolutionary history of mitochondrial tRNA gene loss, transfer, and functional replacement that has created extreme variation in mitochondrial tRNA populations across plant species. We describe emerging tRNA-seq methods with promise for refining our understanding of the expression and subcellular localization of tRNAs. Finally, we summarize current evidence and identify open questions related to coevolutionary changes in nuclear-encoded enzymes that have accompanied turnover in mitochondrial tRNA populations.

RevDate: 2020-03-17

Ozozan OV, Dinc T, Vural V, et al (2020)

An electron microscopy study of liver and kidney damage in an experimental model of obstructive jaundice.

Annali italiani di chirurgia, 91:122-130.

With this experimental study we investigated the consequences of ligation of the common bile duct (CBD) on hepatic cells and on the renal ultrastructure by electron microscopy and also determine the effects after liberation of the ductus joint in order to clarify the mechanisms of renal failure commonly observed in cholestatic liver disease. The study was conducted on 53 Wistar albino rats divided into 4 subgroups. In the comparison group (sham) we proceeded to the simple laparotomy. After preparation of the common bile duct of all the rats of the four groups, and ligation of the duct at the level of the distal third, eight rats in each group were sacrificed on the 3rd, 7th, 10th and 14th day after surgery, taking blood samples to measure the serum levels of ALP and bilirubin, and liver and renal tissue samples for histological evaluation. In four rats of each group the common bile duct was unligated at the same deadlines to obtain free drainage of the bile for a week. At the end of this week, the rats were sacrificed by collecting blood and liver and kidney tissue samples.

RESULTS: after CBD ligation in both groups, the ALP value, total and direct bilurubin levels were proportionally increased. After duct release, bilurubin levels decreased significantly. In group II, while large lipid granules were observed to indicate oxidative damage, mitochondrial swelling and crystals were observed after duct liberation. Areas of glycogen and normal mitochondria were observed in group IV. After duct release in this group, increases in Ito granules, lipid granules and normal mitochondria were observed, which may reflect the evolution of hepatic regeneration. When renal tissue was examined in group II, fusion processes in the feet, thickening of the basement membrane and mesengium were observed, and mitochondrial crystals were observed in renal tissue as well as in the liver after duct release. Damage in group III and group IV was increased parallel to prolongation of jaundice and after loosening persistent damage with mitochondrial crystals.

CONCLUSION: Ultrastructural changes in rat liver tissue in conditions of obstructive jaundice may be reversible after restoration of drainage. On the other hand, ultrastructural changes in renal tissue in cases of prolonged jaundice are irreversible even if the internal drainage is restored.

KEY WORDS: Bile Duct, Liver, Kidney, Obstructive Jaundice.

RevDate: 2020-03-16
CmpDate: 2020-03-16

Caicedo-Garzón V, Salgado-Roa FC, Sánchez-Herrera M, et al (2019)

Genetic diversification of Panstrongylus geniculatus (Reduviidae: Triatominae) in northern South America.

PloS one, 14(10):e0223963.

Triatomines are the vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Although Triatoma and Rhodnius are the most-studied vector genera, other triatomines, such as Panstrongylus, also transmit T. cruzi, creating new epidemiological scenarios. Panstrongylus has at least 13 reported species but there is limited information about its intraspecific genetic variation and patterns of diversification. Here, we begin to fill this gap by studying populations of P. geniculatus from Colombia and Venezuela and including other epidemiologically important species from the region. We examined the pattern of diversification of P. geniculatus in Colombia using mitochondrial and nuclear ribosomal data. Genetic diversity and differentiation were calculated within and among populations of P. geniculatus. Moreover, we constructed maximum likelihood and Bayesian inference phylogenies and haplotype networks using P. geniculatus and other species from the genus (P. megistus, P. lignarius, P. lutzi, P. tupynambai, P. chinai, P. rufotuberculatus and P. howardi). Using a coalescence framework, we also dated the P. geniculatus lineages. The total evidence tree showed that P. geniculatus is a monophyletic species, with four clades that are concordant with its geographic distribution and are partly explained by the Andes orogeny. However, other factors, including anthropogenic and eco-epidemiological effects must be investigated to explain the existence of recent geographic P. geniculatus lineages. The epidemiological dynamics in structured vector populations, such as those found here, warrant further investigation. Extending our knowledge of P. geniculatus is necessary for the accurate development of effective strategies for the control of Chagas disease vectors.

RevDate: 2020-03-11

Hammond MJ, Nenarokova A, Butenko A, et al (2020)

A uniquely complex mitochondrial proteome from Euglena gracilis.

Molecular biology and evolution pii:5803078 [Epub ahead of print].

Euglena gracilis is a metabolically flexible, photosynthetic and adaptable free-living protist of considerable environmental importance and biotechnological value. By label-free LC-MSMS, a total of 1,786 proteins were identified from the E. gracilis purified mitochondria, representing one of the largest mitochondrial proteomes so far described. Despite this apparent complexity, protein machinery responsible for the extensive RNA editing, splicing and processing in the sister clades diplonemids and kinetoplastids, is absent. This strongly suggests that the complex mechanisms of mitochondrial gene expression in diplonemids and kinetoplastids occurred late in euglenozoan evolution, arising independently. By contrast, the alternative oxidase pathway and numerous ribosomal subunits presumed to be specific for parasitic trypanosomes are present in E. gracilis. We investigated the evolution of unexplored protein families, including import complexes, cristae formation proteins and translation termination factors, as well as canonical and unique metabolic pathways. We additionally compare this mitoproteome with the transcriptome of Eutreptiella gymnastica, illuminating conserved features of Euglenida mitochondria as well as those exclusive to E. gracilis. This is the first mitochondrial proteome of a free-living protist from the Excavata, and one of few available for protists as a whole. This study alters our views of the evolution of the mitochondrion, and indicates early emergence of complexity within euglenozoan mitochondria, independent of parasitism.

RevDate: 2020-03-11

Speijer D (2020)

Debating Eukaryogenesis: Part 2: How Anachronistic Reasoning Can Lure Us into Inventing Intermediates.

BioEssays : news and reviews in molecular, cellular and developmental biology [Epub ahead of print].

Eukaryotic origins are inextricably linked with the arrival of a pre-mitochondrion of alphaproteobacterial-like ancestry. However, the nature of the "host" cell and the mode of entry are subject to heavy debate. It is becoming clear that the mutual adaptation of a relatively simple, archaeal host and the endosymbiont has been the defining influence at the beginning of the eukaryotic lineage; however, many still resist such symbiogenic models. In part 1, it is posited that a symbiotic stage before uptake ("pre-symbiosis") seems essential to allow further metabolic integration of the two partners ending in endosymbiosis. Thus, the author argued against phagocytic mechanisms (in which the bacterium is prey or parasite) as the mode of entry. Such positions are still broadly unpopular. Here it is explained why. Evolutionary thinking, especially in the case of eukaryogenesis, is still dominated by anachronistic reasoning, in which highly derived protozoan organisms are seen as in some way representative of intermediate steps during eukaryotic evolution, hence poisoning the debate. This reasoning reflects a mind-set that ignores that Darwinian evolution is a fundamentally historic process. Numerous examples of this kind of erroneous reasoning are given, and some basic precautions against its use are formulated.

RevDate: 2020-03-11

Tomáška Ľ, J Nosek (2020)

Co-evolution in the Jungle: From Leafcutter Ant Colonies to Chromosomal Ends.

Journal of molecular evolution pii:10.1007/s00239-020-09935-3 [Epub ahead of print].

Biological entities are multicomponent systems where each part is directly or indirectly dependent on the others. In effect, a change in a single component might have a consequence on the functioning of its partners, thus affecting the fitness of the entire system. In this article, we provide a few examples of such complex biological systems, ranging from ant colonies to a population of amino acids within a single-polypeptide chain. Based on these examples, we discuss one of the central and still challenging questions in biology: how do such multicomponent consortia co-evolve? More specifically, we ask how telomeres, nucleo-protein complexes protecting the integrity of linear DNA chromosomes, originated from the ancestral organisms having circular genomes and thus not dealing with end-replication and end-protection problems. Using the examples of rapidly evolving topologies of mitochondrial genomes in eukaryotic microorganisms, we show what means of co-evolution were employed to accommodate various types of telomere-maintenance mechanisms in mitochondria. We also describe an unprecedented runaway evolution of telomeric repeats in nuclei of ascomycetous yeasts accompanied by co-evolution of telomere-associated proteins. We propose several scenarios derived from research on telomeres and supported by other studies from various fields of biology, while emphasizing that the relevant answers are still not in sight. It is this uncertainty and a lack of a detailed roadmap that makes the journey through the jungle of biological systems still exciting and worth undertaking.

RevDate: 2020-03-12
CmpDate: 2020-03-12

Liu Y, Qu J, Zhang L, et al (2019)

Identification and characterization of the TCA cycle genes in maize.

BMC plant biology, 19(1):592.

BACKGROUND: The tricarboxylic acid (TCA) cycle is crucial for cellular energy metabolism and carbon skeleton supply. However, the detailed functions of the maize TCA cycle genes remain unclear.

RESULTS: In this study, 91 TCA genes were identified in maize by a homology search, and they were distributed on 10 chromosomes and 1 contig. Phylogenetic results showed that almost all maize TCA genes could be classified into eight major clades according to their enzyme families. Sequence alignment revealed that several genes in the same subunit shared high protein sequence similarity. The results of cis-acting element analysis suggested that several TCA genes might be involved in signal transduction and plant growth. Expression profile analysis showed that many maize TCA cycle genes were expressed in specific tissues, and replicate genes always shared similar expression patterns. Moreover, qPCR analysis revealed that some TCA genes were highly expressed in the anthers at the microspore meiosis phase. In addition, we predicted the potential interaction networks among the maize TCA genes. Next, we cloned five TCA genes located on different TCA enzyme complexes, Zm00001d008244 (isocitrate dehydrogenase, IDH), Zm00001d017258 (succinyl-CoA synthetase, SCoAL), Zm00001d025258 (α-ketoglutarate dehydrogenase, αKGDH), Zm00001d027558 (aconitase, ACO) and Zm00001d044042 (malate dehydrogenase, MDH). Confocal observation showed that their protein products were mainly localized to the mitochondria; however, Zm00001d025258 and Zm00001d027558 were also distributed in the nucleus, and Zm00001d017258 and Zm00001d044042 were also located in other unknown positions in the cytoplasm. Through the bimolecular fluorescent complimentary (BiFC) method, it was determined that Zm00001d027558 and Zm00001d044042 could form homologous dimers, and both homologous dimers were mainly distributed in the mitochondria. However, no heterodimers were detected between these five genes. Finally, Arabidopsis lines overexpressing the above five genes were constructed, and those transgenic lines exhibited altered primary root length, salt tolerance, and fertility.

CONCLUSION: Sequence compositions, duplication patterns, phylogenetic relationships, cis-elements, expression patterns, and interaction networks were investigated for all maize TCA cycle genes. Five maize TCA genes were overexpressed in Arabidopsis, and they could alter primary root length, salt tolerance, and fertility. In conclusion, our findings may help to reveal the molecular function of the TCA genes in maize.

RevDate: 2020-03-11
CmpDate: 2020-03-11

Shiratori T, Suzuki S, Kakizawa Y, et al (2019)

Phagocytosis-like cell engulfment by a planctomycete bacterium.

Nature communications, 10(1):5529.

Phagocytosis is a key eukaryotic feature, conserved from unicellular protists to animals, that enabled eukaryotes to feed on other organisms. It could also be a driving force behind endosymbiosis, a process by which α-proteobacteria and cyanobacteria evolved into mitochondria and plastids, respectively. Here we describe a planctomycete bacterium, 'Candidatus Uab amorphum', which is able to engulf other bacteria and small eukaryotic cells through a phagocytosis-like mechanism. Observations via light and electron microscopy suggest that this bacterium digests prey cells in specific compartments. With the possible exception of a gene encoding an actin-like protein, analysis of the 'Ca. Uab amorphum' genomic sequence does not reveal any genes homologous to eukaryotic phagocytosis genes, suggesting that cell engulfment in this microorganism is probably not homologous to eukaryotic phagocytosis. The discovery of this "phagotrophic" bacterium expands our understanding of the cellular complexity of prokaryotes, and may be relevant to the origin of eukaryotic cells.

RevDate: 2020-03-12
CmpDate: 2020-03-12

Yang H, Deng L, Liu H, et al (2019)

Overexpression of BnaAOX1b Confers Tolerance to Osmotic and Salt Stress in Rapeseed.

G3 (Bethesda, Md.), 9(10):3501-3511.

Alternative oxidases (AOXs) are the terminal oxidase in the cyanide-resistant respiration pathway in plant mitochondria, which play an important role in abiotic stress and are proposed as a functional marker for high tolerant breeding. In this study, ten AOX genes (BnaAOXs) were identified, and CysI and CysII of AOX isoforms were highly conserved in rapeseed. Among them, Bna.AOX1b was mainly expressed in the ovule and displayed varying expression between rapeseed cultivars which showed different salt resistance in seed germination. We identified its mitochondrial localization of this gene. To investigate the function of BnaAOX1b in rapeseed, transgenic rapeseed lines with overexpressed BnaAOX1b were created and seed germination and seedling establishment assays were performed under osmotic, salt, and ABA treatment. The results indicated that overexpression of BnaAOX1b significantly improved seed germination under osmotic and salt stress and weakened ABA sensitivity. In addition, post-germination seedling growth was improved under high salt condition, but showed hypersensitivity to ABA. RNA-sequencing analysis indicated that the genes involved in electron transport or energy pathway were induced and a number of gene responses to salt stress and ABA were regulated in Bna.AOX1b overexpressing seeds. Taken together, our results imply that Bna.AOX1b confers tolerance to osmotic and salt stress in terms of seed germination and seedling establishment by regulating stress responsive genes and the response to ABA, and could be utilized as a candidate gene in transgenic breeding.

RevDate: 2020-03-12
CmpDate: 2020-03-12

Derkarabetian S, Benavides LR, G Giribet (2019)

Sequence capture phylogenomics of historical ethanol-preserved museum specimens: Unlocking the rest of the vault.

Molecular ecology resources, 19(6):1531-1544.

Natural history collections play a crucial role in biodiversity research, and museum specimens are increasingly being incorporated into modern genetics-based studies. Sequence capture methods have proven incredibly useful for phylogenomics, providing the additional ability to sequence historical museum specimens with highly degraded DNA, which until recently have been deemed less valuable for genetic work. The successful sequencing of ultraconserved elements (UCEs) from historical museum specimens has been demonstrated on multiple tissue types including dried bird skins, formalin-fixed squamates and pinned insects. However, no study has thoroughly demonstrated this approach for historical ethanol-preserved museum specimens. Alongside sequencing of "fresh" specimens preserved in >95% ethanol and stored at -80°C, we used extraction techniques specifically designed for degraded DNA coupled with sequence capture protocols to sequence UCEs from historical museum specimens preserved in 70%-80% ethanol and stored at room temperature, the standard for such ethanol-preserved museum collections. Across 35 fresh and 15 historical museum samples of the arachnid order Opiliones, an average of 345 UCE loci were included in phylogenomic matrices, with museum samples ranging from six to 495 loci. We successfully demonstrate the inclusion of historical ethanol-preserved museum specimens in modern sequence capture phylogenomic studies, show a high frequency of variant bases at the species and population levels, and from off-target reads successfully recover multiple loci traditionally sequenced in multilocus studies including mitochondrial loci and nuclear rRNA loci. The methods detailed in this study will allow researchers to potentially acquire genetic data from millions of ethanol-preserved museum specimens held in collections worldwide.


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.

ESP Support

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.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

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.

ESP Usage

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.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )