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β-lactamase enzymes have generated significant interest due to their ability to confer resistance to the most commonly used family of antibiotics in human medicine. Among these enzymes, the class B β-lactamases are members of a superfamily of metallo-β-lactamase (MβL) fold proteins which are characterised by conserved motifs (i.e., HxHxDH) and are not only limited to bacteria. Indeed, as the result of several barriers, including low sequence similarity, default protein annotation, or untested enzymatic activity, MβL fold proteins have long been unexplored in other organisms. However, thanks to search approaches which are more sensitive compared to classical Blast analysis, such as the use of common ancestors to identify distant homologous sequences, we are now able to highlight their presence in different organisms including Bacteria, Archaea, Nanoarchaeota, Asgard, Humans, Giant viruses, and Candidate Phyla Radiation (CPR). These MβL fold proteins are multifunctional enzymes with diverse enzymatic or non-enzymatic activities of which, at least thirteen activities have been reported such as β-lactamase, ribonuclease, nuclease, glyoxalase, lactonase, phytase, ascorbic acid degradation, anti-cancer drug degradation, or membrane transport. In this review, we (i) discuss the existence of MβL fold enzymes in the different domains of life, (ii) present more suitable approaches to better investigating their homologous sequences in unsuspected sources, and (iii) report described MβL fold enzymes with demonstrated enzymatic or non-enzymatic activities. [ABSTRACT FROM AUTHOR]

• Co-infection or co-colonisation of Staphylococcus aureus (S. aureus) and vancomycin-resistant enterococci (VRE) are sources of vanA dissemination. • Three main mechanisms of acquisition of the vanA operon in S. aureus are conjugation, transposition of Tn1546 and enterococcal plasmid integration. • There is a worldwide occurrence of hotspots for vanA -containing plasmid integration via homologous recombination in S. aureus strains. • It is necessary to screen for S. aureus in patients with VRE infections and people in direct contact with them, and test antimicrobial susceptibility of S. aureus for methicillin and vancomycin. Vancomycin is frequently used as a last line of defence against infections due to multidrug-resistant Staphylococcus aureus (S. aureus). A recent finding described the acquisition of vancomycin-resistant S. aureus strains by the integration of an enterococcal plasmid containing the vanA operon into the S. aureus chromosome via homologous recombination involving a specific integration site called locus L2. To characterise all mechanisms of acquisition of vanA , this study analysed the 15 706 S. aureus genomes to look for vanA and described its genetic environment. A complete vanA operon was found in 25 S. aureus strains isolated from 12 patients, including nine co-isolated with vancomycin-resistant Enterococcus strains. VanA was found within transposon Tn1546-like elements on 17 plasmids and eight chromosomes. VanA might be acquired through conjugation of enterococcal and staphylococcal plasmids, transposition of Tn1546 carrying vanA and plasmid integration into the chromosome. Further, L2 was detected in 2087 genomes (13.3%) of S. aureus strains across different continents. Six potential chromosomal hotspots for integration of the entire vanA -containing enterococcal plasmid were identified by homologous recombination via L2. These findings suggest that the recently described scenario in a New York patient could be reproduced anywhere. Surveillance of this possibility is mandatory, especially in patients with vancomycin-resistant Enterococcus infection or colonisation. [Display omitted] [ABSTRACT FROM AUTHOR]

The relationship between human genetic variation and disease has not been fully elucidated. According to the present view on infectious diseases pathogen resistance is linked to human leukocyte antigen (HLA) class I/II variants and their individual capacity to present pathogen-derived peptides. Yet, T cell education in the thymus occurs through negative and positive selection, and both processes are controlled by a combination of HLA class I/II variants and peptides from the self. Therefore, the capacity of given HLA class I/II variants to bind pathogen-derived peptides is only one part of the selective process to generate effective immune responses. We thus propose that peptidome variation contributes to shaping T cell receptor (TCR) repertoires and hence individual immune responses, and that this variation represents inherent modulator epitopes. TCR repertoires emerge in the thymus in each individual as T cells undergo positive and negative selection. T cell education is controlled by the combination of HLA class I/II molecules and their peptide pools (peptidome). HLA class I/II molecules are highly plastic in human populations but the peptidome is also a source of variation. Hence combined diversity of HLA class I/II molecules and of self-peptides shapes individual immune responses. Self-peptide variants that affect T cell repertoires represent inherent modulator epitopes. [ABSTRACT FROM AUTHOR]

The butyrophilin 3 (BTN3) receptors are implicated in the T lymphocytes regulation and present a wide plasticity in mammals. In order to understand how these genes have been diversified, we studied their evolution and show that the three human BTN3 are the result of two successive duplications in Primates and that the three genes are present in Hominoids and the Old World Monkey groups. A thorough phylogenetic analysis reveals a concerted evolution of BTN3 characterized by a strong and recurrent homogenization of the region encoding the signal peptide and the immunoglobulin variable (IgV) domain in Hominoids, where the sequences of BTN3A1 or BTN3A3 are replaced by BTN3A2 sequence. In human, the analysis of the diversity of these genes in 1683 individuals representing 26 worldwide populations shows that the three genes are polymorphic, with more than 46 alleles for each gene, and marked by extreme homogenization of the IgV sequences. The same analysis performed for the BTN2 genes shows also a concerted evolution; however, it is not as strong and recurrent as for BTN3. This study shows that BTN3 receptors are marked by extreme concerted evolution at the IgV domain and that BTN3A2 plays a central role in this evolution. [ABSTRACT FROM AUTHOR]

Background: Horizontal transfer plays an important role in the evolution of bacterial genomes, yet it obeys several constraints, including the ecological opportunity to meet other organisms, the presence of transfer systems, and the fitness of the transferred genes. Bacteria from the Planctomyctetes, Verrumicrobia, Chlamydiae (PVC) super-phylum have a compartmentalized cell plan delimited by an intracytoplasmic membrane that might constitute an additional constraint with particular impact on bacterial evolution. In this investigation, we studied the evolution of 33 genomes from PVC species and focused on the rate and the nature of horizontally transferred sequences in relation to their habitat and their cell plan. Results: Using a comparative phylogenomic approach, we showed that habitat influences the evolution of the bacterial genome's content and the flux of horizontal transfer of DNA (HT). Thus bacteria from soil, from insects and ubiquitous bacteria presented the highest average of horizontal transfer compared to bacteria living in water, extracellular bacteria in vertebrates, bacteria from amoeba and intracellular bacteria in vertebrates (with a mean of 379 versus 110 events per species, respectively and 7.6% of each genomes due to HT against 4.8%). The partners of these transfers were mainly bacterial organisms (94.9%); they allowed us to differentiate environmental bacteria, which exchanged more with Proteobacteria, and bacteria from vertebrates, which exchanged more with Firmicutes. The functional analysis of the horizontal transfers revealed a convergent evolution, with an over-representation of genes encoding for membrane biogenesis and lipid metabolism, among compartmentalized bacteria in the different habitats. Conclusions: The presence of an intracytoplasmic membrane in PVC species seems to affect the genome's evolution through the selection of transferred DNA, according to their encoded functions. [ABSTRACT FROM AUTHOR]

Background: The PVC super-phylum gathers bacteria from seven phyla (Planctomycetes, Verrucomicrobiae, Chlamydiae, Lentisphaera, Poribacteria, OP3, WWE2) presenting different lifestyles, cell plans and environments. Planctomyces and several Verrucomicrobiae exhibit a complex cell plan, with an intracytoplasmic membrane inducing the compartmentalization of the cytoplasm into two regions (pirellulosome and paryphoplasm). The evolution and function of this cell plan is still subject to debate. In this work, we hypothesized that it could play a role in protection of the bacterial DNA, especially against Horizontal Genes Transfers (HGT). Therefore, 64 bacterial genomes belonging to seven different phyla (whose four PVC phyla) were studied. We reconstructed the evolution of the cell plan as precisely as possible, thanks to information obtained by bibliographic study and electronic microscopy. We used a strategy based on comparative phylogenomic in order to determine the part occupied by the horizontal transfers for each studied genomes. Results: Our results show that the bacteria Simkania negevensis (Chlamydiae) and Coraliomargarita akajimensis (Verrucomicrobiae), whose cell plan were unknown before, are compartmentalized, as we can see on the micrographies. This is one of the first indication of the presence of an intracytoplasmic membrane in a Chlamydiae. The proportion of HGT does not seems to be related to the cell plan of bacteria, suggesting that compartmentalization does not induce a protection of bacterial DNA against HGT. Conversely, lifestyle of bacteria seems to impact the ability of bacteria to exchange genes. Conclusions: Our study allows a best reconstruction of the evolution of intracytoplasmic membrane, but this structure seems to have no impact on HGT occurrences. [ABSTRACT FROM AUTHOR]

Background: Rickettsia species are strictly intracellular bacteria that have undergone a reductive genomic evolution. Despite their allopatric lifestyle, almost half of the 26 currently validated Rickettsia species have plasmids. In order to study the origin, evolutionary history and putative roles of rickettsial plasmids, we investigated the evolutionary processes that have shaped 20 plasmids belonging to 11 species, using comparative genomics and phylogenetic analysis between rickettsial, microbial and non-microbial genomes. Results: Plasmids were differentially present among Rickettsia species. The 11 species had 1 to 4 plasmid (s) with a size ranging from 12 kb to 83 kb. We reconstructed pRICO, the last common ancestor of the current rickettsial plasmids. pRICO was vertically inherited mainly from Rickettsia/Orientia chromosomes and diverged vertically into a single or multiple plasmid(s) in each species. These plasmids also underwent a reductive evolution by progressive gene loss, similar to that observed in rickettsial chromosomes, possibly leading to cryptic plasmids or complete plasmid loss. Moreover, rickettsial plasmids exhibited ORFans, recent gene duplications and evidence of horizontal gene transfer events with rickettsial and non-rickettsial genomes mainly from the α/γ-proteobacteria lineages. Genes related to maintenance and plasticity of plasmids, and to adaptation and resistance to stress mostly evolved under vertical and/or horizontal processes. Those involved in nucleotide/carbohydrate transport and metabolism were under the influence of vertical evolution only, whereas genes involved in cell wall/membrane/envelope biogenesis, cycle control, amino acid/lipid/coenzyme and secondary metabolites biosynthesis, transport and metabolism underwent mainly horizontal transfer events. Conclusion: Rickettsial plasmids had a complex evolution, starting with a vertical inheritance followed by a reductive evolution associated with increased complexity via horizontal gene transfer as well as gene duplication and genesis. The plasmids are plastic and mosaic structures that may play biological roles similar to or distinct from their co-residing chromosomes in an obligate intracellular lifestyle. [ABSTRACT FROM AUTHOR]

We propose a new hypothesis that explains the maintenance and evolution of MHC polymorphism. It is based on two phenomena: the constitution of the repertoire of naive T lymphocytes and the evolution of the pathogen and its impact on the immune memory of T lymphocytes. Concerning the latter, pathogen evolution will have a different impact on reinfection depending on the MHC allomorph. If a mutation occurs in a given region, in the case of MHC allotypes, which do not recognize the peptide in this region, the mutation will have no impact on the memory repertoire. In the case where the MHC allomorph binds to the ancestral peptides and not to the mutated peptide, that individual will have a higher chance of being reinfected. This difference in fitness will lead to a variation of the allele frequency in the next generation. Data from the SARS-CoV-2 pandemic already support a significant part of this hypothesis and following up on these data may enable it to be confirmed. This hypothesis could explain why some individuals after vaccination respond less well than others to variants and leads to predict the probability of reinfection after a first infection depending upon the variant and the HLA allomorph. [ABSTRACT FROM AUTHOR]

Highlights: [•] A high amount of random transfers of DNA sequences can occur independently of gene functions or sequence lengths. [•] Lateral sequence transfers have occurred between alphaproteobacteria and other bacteria and between alphaproteobacteria and archaea. [•] Transfers from alphaproteobacteria to eukaryotes play a critical role in the genealogy of eukaryotes. [ABSTRACT FROM AUTHOR]

Understanding the evolutionary plasticity of the genome requires a global, comparative approach in which genetic events are considered both in a phylogenetic framework and with regard to population genetics and environmental variables. In the mechanisms that generate adaptive and non-adaptive changes in genomes, segmental duplications (duplication of individual genes or genomic regions) and polyploidization (whole genome duplications) are well-known driving forces. The probability of fixation and maintenance of duplicates depends on many variables, including population sizes and selection regimes experienced by the corresponding genes: a combination of stochastic and adaptive mechanisms has shaped all genomes. A survey of experimental work shows that the distinction made between fixation and maintenance of duplicates still needs to be conceptualized and mathematically modeled. Here we review the mechanisms that increase or decrease the probability of fixation or maintenance of duplicated genes, and examine the outcome of these events on the adaptation of the organisms. [ABSTRACT FROM AUTHOR]

Background: The Nme gene family is involved in multiple physiological and pathological processes such as cellular differentiation, development, metastatic dissemination, and cilia functions. Despite the known importance of Nme genes and their use as clinical markers of tumor aggressiveness, the associated cellular mechanisms remain poorly understood. Over the last 20 years, several non-vertebrate model species have been used to investigate Nme functions. However, the evolutionary history of the family remains poorly understood outside the vertebrate lineage. The aim of the study was thus to elucidate the evolutionary history of the Nme gene family in Metazoans. Methodology/Principal Findings: Using a total of 21 eukaryote species including 14 metazoans, the evolutionary history of Nme genes was reconstructed in the metazoan lineage. We demonstrated that the complexity of the Nme gene family, initially thought to be restricted to chordates, was also shared by the metazoan ancestor. We also provide evidence suggesting that the complexity of the family is mainly a eukaryotic innovation, with the exception of Nme8 that is likely to be a choanoflagellate/metazoan innovation. Highly conserved gene structure, genomic linkage, and protein domains were identified among metazoans, some features being also conserved in eukaryotes. When considering the entire Nme family, the starlet sea anemone is the studied metazoan species exhibiting the most conserved gene and protein sequence features with humans. In addition, we were able to show that most of the proteins known to interact with human NME proteins were also found in starlet sea anemone. Conclusion/Significance: Together, our observations further support the association of Nme genes with key cellular functions that have been conserved throughout metazoan evolution. Future investigations of evolutionarily conserved Nme gene functions using the starlet sea anemone could shed new light on a wide variety of key developmental and cellular processes. [ABSTRACT FROM AUTHOR]

The recent availability of the complete genome sequences of a large number of model organisms, together with the immense amount of data being produced by the new high-throughput technologies, means that we can now begin comparative analyses to understand the mechanisms involved in the evolution of the genome and their consequences in the study of biological systems. Phylogenetic approaches provide a unique conceptual framework for performing comparative analyses of all this data, for propagating information between different systems and for predicting or inferring new knowledge. As a result, phylogeny-based inference systems are now playing an increasingly important role in most areas of high throughput genomics, including studies of promoters (phylogenetic footprinting), interactomes (based on the presence and degree of conservation of interacting proteins), and in comparisons of transcriptomes or proteomes (phylogenetic proximity and co-regulation/co-expression). Here we review the recent developments aimed at making automatic, reliable phylogenybased inference feasible in large-scale projects. We also discuss how evolutionary concepts and phylogeny-based inference strategies are now being exploited in order to understand the evolution and function of biological systems. Such advances will be fundamental for the success of the emerging disciplines of systems biology and synthetic biology, and will have wide-reaching effects in applied fields such as biotechnology, medicine and pharmacology. [ABSTRACT FROM AUTHOR]

Reconstructing the evolutionary history of all species is an essential objective for evolutionary biologists. Much effort has been devoted to ancestral genome reconstruction. Numbered genome sequencing of current and extinct organisms enables evolutionary biologists to compare genomic data and reconstruct ancestral genomes. Long-term conservation of karyotype, gene order or gene sequence are clues to the heritage of each species and these data can be used by evolutionary biologists to synthesize distant ancestral genomes. In this review, we referred to the recent advances in ancestral genomes reconstruction and the insight it gives on genome evolution. Special attention is devoted to the use of this knowledge to understand the evolution of the immune system genes. [Copyright &y& Elsevier]

In this article, we describe how we reconstructed a precise, minimal proto-MHC region in the ancestor of euchordates, which was based on a comparison of the MHC-paralogy group of vertebrate with the MHC-like chromosome of cephalochordates. This deduced ancestral region was compared with the genomes of extant species, other deuterostomes and protostomes. Our analysis revealed statistically significant traces of conservation in these species, suggesting that a proto-MHC region existed at the origin of all bilaterian species. We also propose a new approach to reconstruct ancestral genomes, which combines both stringent statistical testing and phylogenetic analysis. [Copyright &y& Elsevier]

Identification of conserved genomic regions between different species is crucial for the reconstruction of their last common ancestor. Indeed, such regions of conservation in today’s species (if not due to chance) may either constitute stigmata of an ancestrally conserved region or result from a series of independent convergent events. The more phylogenetically distant the compared species are, the more we expect rearrangements and thus difficulties in finding regions of conservation. Here we decipher with strong evidence conserved genomic regions between vertebrates (human and zebrafish) and arthropods (DrosophilaandAnopheles). This work includes a robust phylogenetic analysis in conjunction with a stringent statistical testing that allowed the significant rejection of a “by chance” conservation hypothesis. The conservation of gene clusters across four different species from two phylogenetically distant groups makes the hypothesis of an ancestral conservation more likely and parsimonious than the hypothesis of individual convergent events. This result shows that, in spite of more than 800 million years of divergence and evolution from their last common ancestor, we can still reveal stigmata of conservation between all these species. The last common ancestor of zebrafish, human,Drosophila, andAnophelesis the common ancestor of all protostomes and deuterostomes known as “Urbilateria.” This study reveals clusters of probably ancestrally conserved genes and constitutes an advance toward the reconstruction of the genome ofUrbilateria. Thus this work allows a better understanding of the evolutionary history of metazoan genomes, including our genome. [ABSTRACT FROM AUTHOR]

Recently, the LAP (for ‘LRR and PDZ’) family of adaptor proteins was described in vertebrates and invertebrates. The proteins are involved in cell polarity and receptor targeting, and they contain both LRR and PDZ domains in the same molecule, a combination that is specifically bilaterian. A search of available genome sequences reveals a limited number of lap genes, which we have classified by phylogenetic analysis. We propose a functional hypothesis for the origin of this protein family in bilaterians, and give a phylogenetic interpretation of their diversity. [ABSTRACT FROM AUTHOR]

The IL-17 pathway displays remarkably diverse functional modes between different subphyla, classes, and even orders, yet its driving factors remains elusive. Here, we demonstrate that the IL-17 pathway originated through domain shuffling between a Toll-like receptor (TLR)/IL-1R pathway and a neurotrophin-RTK (receptor-tyrosine-kinase) pathway (a Trunk-Torso pathway). Unlike other new pathways that evolve independently, the IL-17 pathway remains intertwined with its donor pathways throughout later evolution. This intertwining not only influenced the gains and losses of domains and components in the pathway but also drove the diversification of the pathway's functional modes among animal lineages. For instance, we reveal that the crustacean female sex hormone, a neurotrophin inducing sex differentiation, could interact with IL-17Rs and thus be classified as true IL-17s. Additionally, the insect prothoracicotropic hormone, a neurotrophin initiating ecdysis in Drosophila by binding to Torso, could bind to IL-17Rs in other insects. Furthermore, IL-17R and TLR/IL-1R pathways maintain crosstalk in amphioxus and zebrafish. Moreover, the loss of the Death domain in the pathway adaptor connection to IκB kinase and stress-activated protein kinase (CIKSs) dramatically reduced their abilities to activate nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) in amphioxus and zebrafish. Reinstating this Death domain not only enhanced NF-κB/ AP-1 activation but also strengthened anti-bacterial immunity in zebrafish larvae. This could explain why the mammalian IL-17 pathway, whose CIKS also lacks Death, is considered a weak signaling activator, relying on synergies with other pathways. Our findings provide insights into the functional diversity of the IL-17 pathway and unveil evolutionary principles that could govern the pathway and be used to redesign and manipulate it. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex (MHC) genes (referred to as human leukocyte antigen or HLA in humans) are a key component of vertebrate immune systems, coding for proteins which present antigens to T‐cells. These genes are outstanding in their degree of polymorphism, with important consequences for human and animal health. The polymorphism is thought to arise from selection pressures imposed by pathogens on MHC allomorphs, which differ in their antigen‐binding capacity. However, the existing theory has not considered MHC selection in relation to the formation of immune memory. In this paper, we argue that this omission limits our understanding of the evolution of MHC polymorphism and its role in disease. We review recent evidence that has emerged from the massive research effort related to the SARS‐CoV‐2 pandemics, and which provides new evidence for the role of MHC in shaping immune memory. We then discuss why the inclusion of immune memory within the existing theory may have non‐trivial consequence for our understanding of the evolution of MHC polymorphism. Finally, we will argue that neglecting immune memory hinders our interpretation of empirical findings, and postulate that future studies focusing on pathogen‐driven MHC selection would benefit from stratifying the available data according to the history of infection (and vaccination, if relevant). [ABSTRACT FROM AUTHOR]

Two different adaptive immune systems (AIS) are present in the two phyla of vertebrates (jawed vertebrates and cyclostomes). The jawed vertebrate system is based on IG/TCR/RAG/MHC while the cyclostome system is based on VLRCs and AID-like enzymes both systems using homologous Cell types (B-cell and B-cell Like, T-cell and T-cell like). We will present our current view of the evolution of these two AISs and present alternative hypotheses that could explain the apparent convergent evolution of the two systems. We will also discuss why comparative immunology analyses should be based on evolutionary biology approaches and not on the scale of progress one. [ABSTRACT FROM AUTHOR]

The phylum Cnidaria is usually divided into five classes: Anthozoa, Cubozoa, Hydrozoa, Scyphozoa and Staurozoa. The class Anthozoa is subdivided into two subclasses: Hexacorallia and Octocorallia. Morphological and molecular studies based on nuclear rDNA and recent phylogenomic studies support the monophyly of Anthozoa. On the other hand, molecular studies based on mitochondrial markers, including two recent studies based on mitogenomic data, supported the paraphyly of Anthozoa, and positioned Octocorallia as sister group to Medusozoa (the monophyletic group of Cubozoa, Hydrozoa and Scyphozoa). On the basis of 51 nuclear orthologs from four hexacorallians, four octocorallians, two hydrozoans and one scyphozoan (with poriferans and Homo sapiens as out-groups), we built a multilocus alignment of 9 873 amino acids, which aimed at minimizing missing data and hidden paralogy, in order to understand the discrepancy between nuclear and mitochondrial phylogenies. Our phylogenetic analyses strongly supported the monophyly of Anthozoa. We compared the level of substitution saturation between our data set, the data sets of two recent phylogenomic studies and one of a mitogenomic study. We found that mitochondrial DNA is more saturated than nuclear DNA at all the phylogenetic levels studied. Our results emphasize the need for a good evaluation of phylogenetic signal. [ABSTRACT FROM AUTHOR]

Mimivirus and other giant viruses are visible by light microscopy and bona fide microbes that differ from other viruses and from cells that have a ribosome. They can be defined by: giant virion and genome sizes; their complexity, with the presence of DNA and mRNAs and dozens or hundreds of proteins in virions; the presence of translation-associated components; a mobilome including (pro)virophages (and a defence mechanism, named MIMIVIRE, against them) and transpovirons; their monophyly; the presence of the most archaic protein motifs they share with cellular organisms but not other viruses; a broader host range than other viruses. These features show that giant viruses are specific, autonomous, biological entities that warrant the creation of a new branch of microbes. [ABSTRACT FROM AUTHOR]

Circadian rhythms are present in almost all living organisms, and their activity relies on molecular clocks. In prokaryotes, a functional molecular clock has been defined only in cyanobacteria. Here, we investigated the presence of circadian rhythms in non-cyanobacterial prokaryotes. The bioinformatic approach was used to identify a homologue of KaiC (circadian gene in cyanobacteria) in Escherichia coli. Then, strains of E. coli (wild type and mutants) were grown on blood agar, and sampling was made every 3 h for 24 h at constant conditions. Gene expression was determined by qRT-PCR, and the rhythmicity was analyzed using the Cosinor model. We identified RadA as a KaiC homologue in E. coli. Expression of radA showed a circadian rhythm persisting at least 3 days, with a peak in the morning. The circadian expression of other E. coli genes was also observed. Gene circadian oscillations were lost in radA mutants of E. coli. This study provides evidence of molecular clock gene expression in E. coli with a circadian rhythm. Such a finding paves the way for new perspectives in antibacterial treatment. [ABSTRACT FROM AUTHOR]

Abstract: Hybridization is increasingly seen as an important source of adaptive genetic variation and biotic diversity. Recent phylogenetic studies on the early evolution of birds suggest that the early diversification of neoavian orders perhaps involved a period of extensive hybridization or incomplete lineage sorting. Phylogenetic error, saturation, long-branch attraction, and convergence make it difficult to detect ancient hybridization events and differentiate them from incomplete lineage sorting using sequence data. We used recently published retroposon marker data to visualize the early radiation of Neoaves within a phylogenetic network approach, and found that the most basal neoavian taxa indeed show a complex pattern of reticulated relationships. Moreover, the reticulation levels of different parts of the network are consistent with the insertion pattern of the retroposon elements. The use of network-based analyses on homoplasy-free data shows true conflicting signals and the taxa involved that are not represented in trees. [Copyright &y& Elsevier]

A well-established ancestral gene can usually be found, in one or multiple copies, in different descendant species. Sometimes during the course of evolution, all the representatives of a well-established ancestral gene disappear in specific lineages; such gene losses may occur in the genome by deletion of a DNA fragment or by pseudogenization. The loss of an entire gene family in a given lineage may reflect an important phenomenon, and could be due either to adaptation, or to a relaxation of selection that leads to neutral evolution. Therefore, the lineage-specific gene loss analyses are important to improve the understanding of the evolutionary history of genes and genomes. In order to perform this kind of study from the increasing number of complete genome sequences available, we developed a unique new software module called GLADX in the DAGOBAH framework, based on a comparative genomic approach. The software is able to automatically detect, for all the species of a phylum, the presence/absence of a representative of a well-established ancestral gene, and by systematic steps of re-annotation, confirm losses, detect and analyze pseudogenes and find novel genes. The approach is based on the use of highly reliable gene phylogenies, of protein predictions and on the analysis of genomic mutations. All the evidence associated to evolutionary approach provides accurate information for building an overall view of the evolution of a given gene in a selected phylum. The reliability of GLADX has been successfully tested on a benchmark analysis of 14 reported cases. It is the first tool that is able to fully automatically study the lineage-specific losses and pseudogenizations. [ABSTRACT FROM AUTHOR]

Free-living protozoa allow horizontal gene transfer with and between the microorganisms that they host. They host mycobacteria for which the sources of transferred genes remain unknown. Using BLASTp, we searched within the genomes of 15 mycobacteria for homologous genes with 34 amoeba-resistant bacteria and the free-living protozoa Dictyostelium discoideum. Subsequent phylogenetic analysis of these sequences revealed that eight mycobacterial open-reading frames (ORFs) were probably acquired via horizontal transfer from beta- and gamma-Proteobacteria and from Firmicutes, but the transfer histories could not be reliably established in details. One further ORF encoding a pyridine nucleotide disulfide oxidoreductase (pyr-redox) placed non-tuberculous mycobacteria in a clade with Legionella spp., Francisella spp., Coxiella burnetii, the ciliate Tetrahymena thermophila and D. discoideum with a high reliability. Co-culturing Mycobacterium avium and Legionella pneumophila with the amoeba Acanthamoeba polyphaga demonstrated that these two bacteria could live together in amoebae for five days, indicating the biological relevance of intra-amoebal transfer of the pyr-redox gene. In conclusion, the results of this study support the hypothesis that protists can serve as a source and a place for gene transfer in mycobacteria. [ABSTRACT FROM AUTHOR]

Abstract: Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits. Reviewers: This article was reviewed by Jerzy Jurka, Pierre Pontarotti and. For the complete reviews, see the Reviewers' Reports section. [ABSTRACT FROM AUTHOR]

Background: Genome size and gene content in bacteria are associated with their lifestyles. Obligate intracellular bacteria (i.e., mutualists and parasites) have small genomes that derived from larger free-living bacterial ancestors; however, the different steps of bacterial specialization from free-living to intracellular lifestyle have not been studied comprehensively. The growing number of available sequenced genomes makes it possible to perform a statistical comparative analysis of 317 genomes from bacteria with different lifestyles. Results: Compared to free-living bacteria, host-dependent bacteria exhibit fewer rRNA genes, more split rRNA operons and fewer transcriptional regulators, linked to slower growth rates. We found a function-dependent and non-random loss of the same 100 orthologous genes in all obligate intracellular bacteria. Thus, we showed that obligate intracellular bacteria from different phyla are converging according to their lifestyle. Their specialization is an irreversible phenomenon characterized by translation modification and massive gene loss, including the loss of transcriptional regulators. Although both mutualists and parasites converge by genome reduction, these obligate intracellular bacteria have lost distinct sets of genes in the context of their specific host associations: mutualists have significantly more genes that enable nutrient provisioning whereas parasites have genes that encode Types II, IV, and VI secretion pathways. Conclusion: Our findings suggest that gene loss, rather than acquisition of virulence factors, has been a driving force in the adaptation of parasites to eukaryotic cells. This comparative genomic analysis helps to explore the strategies by which obligate intracellular genomes specialize to particular host-associations and contributes to advance our knowledge about the mechanisms of bacterial evolution. [ABSTRACT FROM AUTHOR]

Background: Gene losses played a role which may have been as important as gene and genome duplications and rearrangements, in modelling today species' genomes from a common ancestral set of genes. The set and diversity of protein-coding genes in a species has direct output at the functional level. While gene losses have been reported in all the major lineages of the metazoan tree of life, none have proposed a focus on specific losses in the vertebrates and mammals lineages. In contrast, genes lost in protostomes (i.e. arthropods and nematodes) but still present in vertebrates have been reported and extensively detailed. This probable over-anthropocentric way of comparing genomes does not consider as an important phenomena, gene losses in species that are usually described as "higher". However reporting universally conserved genes throughout evolution that have recently been lost in vertebrates and mammals could reveal interesting features about the evolution of our genome, particularly if these losses can be related to losses of capability. Results: We report 11 gene families conserved throughout eukaryotes from yeasts (such as Saccharomyces cerevisiae) to bilaterian animals (such as Drosophila melanogaster or Caenorhabditis elegans). This evolutionarily wide conservation suggests they were present in the last common ancestors of fungi and metazoan animals. None of these 11 gene families are found in human nor mouse genomes, and their absence generally extends to all vertebrates. A total of 8 out of these 11 gene families have orthologs in plants, suggesting they were present in the Last Eukaryotic Common Ancestor (LECA). We investigated known functional information for these 11 gene families. This allowed us to correlate some of the lost gene families to loss of capabilities. Conclusion: Mammalian and vertebrate genomes lost evolutionary conserved ancestral genes that are probably otherwise not dispensable in eukaryotes. Hence, the human genome, which is generally viewed as being the result of increased complexity and gene-content, has also evolved through simplification and gene losses. This acknowledgement confirms, as already suggested, that the genome of our far ancestor was probably more complex than ever considered. [ABSTRACT FROM AUTHOR]

Within the ‘success story’ of vertebrate evolution, the acquisition and refinement of the adaptive immune system is far from the least impressive example of co-evolution. Members of the tumour necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) have crucial roles in both innate and adaptive immunity. Here, we propose a detailed description of the phylogenetic relations of the TNFSF and TNFRSF members and offer evidence that the divergence of the TNFSF and TNFRSF families paralleled the emergence of the adaptive immune system, at least partly through en bloc duplication. Unexpectedly, TNFSF subfamilies form monophyletic groups with shared functions, including TNFRSF usage. Finally, the mechanisms of (co-)evolution of TNFSF and TNFRSF are discussed. [Copyright &y& Elsevier]

Thienamycin, the first representative of carbapenem antibiotics was discovered in the mid-1970s from soil microorganism, Streptomyces cattleya, during the race to discover inhibitors of bacterial peptidoglycan synthesis. Chemically modified into imipenem (N-formimidoyl thienamycin), now one of the most clinically important antibiotics, thienamycin is encoded by a thienamycin gene cluster composed of 22 genes (thnA to thnV) from S. cattleya NRRL 8057 genome. Interestingly, the role of all thn-genes has been experimentally demonstrated in the thienamycin biosynthesis, except thnS, despite its annotation as putative β-lactamase. Here, we expressed thnS gene and investigated its activities against various substrates. Our analyses revealed that ThnS belonged to the superfamily of metallo-β-lactamase fold proteins. Compared to known β-lactamases such as OXA-48 and NDM-1, ThnS exhibited a lower affinity and less efficiency toward penicillin G and cefotaxime, while imipenem is more actively hydrolysed. Moreover, like most MBL fold enzymes, additional enzymatic activities of ThnS were detected such as hydrolysis of ascorbic acid, single strand DNA, and ribosomal RNA. ThnS appears as a MBL enzyme with multiple activities including a specialised β-lactamase activity toward imipenem. Thus, like toxin/antitoxin systems, the role of thnS gene within the thienamycin gene cluster appears as an antidote against the produced thienamycin. [ABSTRACT FROM AUTHOR]

Proteins with a metallo-beta-lactamase (MBL) fold have been largely studied in bacteria in the framework of resistance to beta-lactams, but their spectrum of activities is broader. We show here that the giant Tupanvirus also encodes a MBL fold-protein that has orthologs in other giant viruses, a deep phylogenetic root and is clustered with tRNases. This protein is significantly associated with translation components in giant viruses. After expression in Escherichia coli, it was found to hydrolyse nitrocefin, a beta-lactam, and penicillin G. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, the tupanvirus MBL fold-protein was not active on single- or double-stranded DNA, but degraded RNAs from bacteria and Acanthamoeba castellanii, the tupanvirus amoebal host. This activity was not neutralized by sulbactam. Overall, our results still broaden the host range of MBL fold-proteins, showing dual beta-lactamase/nuclease activities in giant viruses. [ABSTRACT FROM AUTHOR]

How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular pattern(s) (PAMPs) being presented by molecule(s) on one cell to specific receptor(s) on other cells, much like MHC molecules and T cell receptors (TCRs). In this model, mutations in MHC-like molecule(s) that bound new PAMP(s) would not be recognized by original TCR-like molecule(s), and new MHC-like gene(s) would be lost by neutral drift. Integrating recombination activating gene (RAG) transposon(s) in a TCR-like gene would result in greater recognition diversity, with new MHC-like variants recognized and selected, along with a new RAG/TCR-like system. MHC genes would be selected to present many peptides, through multigene families, allelic polymorphism, and peptide-binding promiscuity. RAG evolved from a DDE transposon present in the ancestor of bilaterian animals; it evolved in a vertical manner and was domesticated as RAG in a jawed vertebrate ancestor. This RAG-like transposon belonged to a transposon family with an ability to create palindromic (P) diversity. A proposed model is that the jawed vertebrate ancestor possessed a complex and powerful innate immune system, where the pre-MHC molecule was able to bind and present certain PAMP molecules to a monomorphic, non-rearranging TCR-like molecule. The integration of the RAG transposon in the recognition module of the TCR-like gene may have led to a significant increase in recognition possibilities, presumably allowing new MHC-like variants to be selected. Hypothetically, the increase in recognition possibilities may have also led to the appearance of MHC polymorphisms and an increase in peptide-binding repertoires (promiscuity). [ABSTRACT FROM AUTHOR]

Background: V(D) J recombination is essential for adaptive immunity in jawed vertebrates and is initiated by the RAG1-RAG2 endonuclease. The RAG1 and RAG2 genes are thought to have evolved from a RAGL (RAG-like) transposon containing convergently-oriented RAG1-like (RAG1L) and RAG2-like (RAG2L) genes. Elements resembling this presumptive evolutionary precursor have thus far only been detected convincingly in deuterostomes, leading to the model that the RAGL transposon first appeared in an early deuterostome. Results: We have identified numerous RAGL transposons in the genomes of protostomes, including oysters and mussels (phylum Mollusca) and a ribbon worm (phylum Nemertea), and in the genomes of several cnidarians. Phylogenetic analyses are consistent with vertical evolution of RAGL transposons within the Bilateria clade and with its presence in the bilaterian ancestor. Many of the RAGL transposons identified in protostomes are intact elements containing convergently oriented RAG1L and RAG2L genes flanked by terminal inverted repeats (TIRs) and target site duplications with striking similarities with the corresponding elements in deuterostomes. In addition, protostome genomes contain numerous intact RAG1L-RAG2L adjacent gene pairs that lack detectable flanking TIRs. Domains and critical active site and structural amino acids needed for endonuclease and transposase activity are present and conserved in many of the predicted RAG1L and RAG2L proteins encoded in protostome genomes. Conclusions: Active RAGL transposons were present in multiple protostome lineages and many were likely transmitted vertically during protostome evolution. It appears that RAGL transposons were broadly active during bilaterian evolution, undergoing multiple duplication and loss/fossilization events, with the RAGL genes that persist in present day protostomes perhaps constituting both active RAGL transposons and domesticated RAGL genes. Our findings raise the possibility that the RAGL transposon arose earlier in evolution than previously thought, either in an early bilaterian or prior to the divergence of bilaterians and non-bilaterians, and alter our understanding of the evolutionary history of this important group of transposons. [ABSTRACT FROM AUTHOR]

Bacterial resistance to antibiotics is a serious medical and public health concern worldwide. Such resistance is conferred by a variety of mechanisms, but the extensive variability in levels of resistance across bacteria is a common finding. Understanding the underlying evolutionary processes governing this functional variation in antibiotic resistance is important as it may allow the development of appropriate strategies to improve treatment options for bacterial infections. The main objective of this study was to examine the functional evolution of β‐lactamases, a common mechanism of enzymatic resistance that inactivates a widely used class of antibiotics. We first obtained β‐lactamase protein sequences and minimal inhibitory concentration (MIC), a measure of antibiotic function, from previously published literature. We then used a molecular phylogenetic framework to examine the evolution of β‐lactamase functional activity. We found that the functional activity of antibiotic resistance mediated by β‐lactamase has evolved in a convergent manner within molecular classes, but is not associated with any single amino acid substitution. This suggests that the dynamics of convergent evolution in this system can vary between the functional and molecular (sequence) levels. Such disassociation may hamper bioinformatic approaches to antibiotic resistance determination and underscore the need for (less efficient but more effective) activity assays as an essential step in evaluating resistance in a given case. [ABSTRACT FROM AUTHOR]

• We explored worldwide genetic diversity and linkage disequilibrium for HLA-A,- E, -F, -G and -H. • Eleven novel HLA-H alleles were identified and validated, two of which possibly encoding a functional HLA protein. • We observed high LD between HLA-H and -A, and HLA-H and -G, and distinct worldwide allelic distribution of these genes. • Conversely, HLA-E and HLA-F had low LD, low allelic diversity and practically no difference in their distribution worlwide. The classical HLA class I genes (HLA Ia) were extensively studied because of their implication in clinical fields and anthropology. Less is known about worldwide genetic diversity and linkage disequilibrium for non-classical HLA class I genes (HLA Ib) and HLA pseudogenes. Notably, HLA-H, which is deleted in a fraction of the population, remains scarcely explored. The aims of this study were 1/ to get further insight into HLA-H genetic diversity and into how this variability potentially affects its expression and 2/ to define HLA Ib worldwide allelic diversity and linkage. Exome sequence data from the 1000 Genomes Project were used to define second field HLA-A, -E, -F, -G and -H typing using PolyPheMe software. Allelic and two-loci haplotype frequencies were estimated using Gene[Rate] software both at worldwide and continental levels. Eleven novel HLA-H alleles identified in exome data were validated by NGS performed on 25 genomic DNA samples from the same cohort. Phylogenetic analysis and frequency distribution of HLA-H alleles revealed three clades, each predominantly represented in Admixed American, European and East Asian populations, African populations and South Asian populations. Among these eleven novel alleles, two potentially encode complete transmembrane HLA proteins. We confirm the high LD between HLA-H and -A, and between HLA-H and -G , and show the three genes have distinct worldwide allelic distribution. Conversely, HLA-E and HLA-F both showed little LD, displayed restricted allelic diversity and practically no difference in their distribution across the planet. Our work thus reveals an unexpectedly high HLA-H genetic diversity, with alleles highly represented in Asia possibly encoding a functional HLA protein. Functional implication of these results remains to be explored, both in physiological and pathological contexts. [ABSTRACT FROM AUTHOR]

Defining worldwide human genetic variation is a critical step to reveal how genome plasticity contributes to disease. Yet, there is currently no metric to assess the representativeness and completeness of current and widely used data on genetic variation. We show here that Human Leukocyte Antigen (HLA) genes can serve as such metric as they are both the most polymorphic and the most studied genetic system. As a test case, we investigated the 1,000 Genomes Project panel. Using high-accuracy in silico HLA typing, we find that over 20% of the common HLA variants and over 70% of the rare HLA variants are missing in this reference panel for worldwide genetic variation, due to undersampling and incomplete geographical coverage, in particular in Oceania and West Asia. Because common and rare variants both contribute to disease, this study thus illustrates how HLA diversity can detect and help fix incomplete sampling and hence accelerate efforts to draw a comprehensive overview of the genetic variation that is relevant to health and disease. [ABSTRACT FROM AUTHOR]

While genetic evidence points towards an absence of Toll-Like Receptors (TLRs) in Platyhelminthes, the Toll/IL-1 Receptor (TIR)-domains that drive the assembly of signalling complexes downstream TLR are present in these organisms. Here, we undertook the characterisation of the repertoire of TIR-domain containing proteins in Schmidtea mediterranea in order to gain valuable information on TLR evolution in metazoan. We report the presence of twenty proteins containing between one and two TIR domains. In addition, our phylogenetic-based reconstruction approach identified Smed-SARM and Smed-MyD88 as conserved TLR adaptors. [ABSTRACT FROM AUTHOR]

Downstream of Kinase (DOK) proteins represent a multigenic family of adaptors that includes negative regulators of immune cell signaling. Using phylogenetics and intron/exon structure data, we show here that the seven human DOK genes ( DOK1 to DOK7 ) form three highly divergent groups that emerged before the protostome-deuterostome split: DOK1/2/3 , DOK4/5/6 , and DOK7 . For two of these three groups ( DOK1/2/3 and DOK4/5/6 ), further gene duplications occurred in vertebrates and so while chordates only have three DOK genes, vertebrates have seven DOK genes over the three groups. From our expression analysis in humans, we show that each group of DOK genes has a distinct pattern of expression. The DOK1/2/3 group is immune specific, yet each of the three genes in the group has a distinct pattern of expression in immune cells. This immune specificity could thus be ancestral, with the DOK1/2/3 gene also being immune-related in protostomes. The DOK4/5/6 and DOK7 groups represent genes that are much less expressed in immune system than the DOK1/2/3 group. Interestingly, we identify a novel tyrosine based motif that is specific to the vertebrate DOK4 /5/6 sequences. The evolution of the DOK genes is thus marked by a pattern of ancient duplications and functional specializations. [ABSTRACT FROM AUTHOR]

β-lactamases are enzymes which are commonly produced by bacteria and which degrade the β-lactam ring of β-lactam antibiotics, namely penicillins, cephalosporins, carbapenems, and monobactams, and inactivate these antibiotics. We performed a rational and comprehensive investigation of β-lactamases in different biological databases. In this study, we constructed hidden Markov model profiles as well as the ancestral sequence of four classes of b-lactamases (A, B, C, and D), which were used to identify potential β-lactamases from environmental metagenomic (1206), human microbiome metagenomic (6417), human microbiome reference genome (1310), and NCBI's nonredundant databases (44101). Our analysis revealed the existence of putative β-lactamases in the metagenomic databases, which appeared to be similar to the four different molecular classes (A-D). This is the first report on the large-scale phylogenetic diversity of new members of β-lactamases, and our results revealed that metagenomic database dark-matter contains β-lactamase-like antibiotic resistance genes. [ABSTRACT FROM AUTHOR]

Genome remodeling and exchange of sequences are widespread in the prokaryotic world and mosaic genomes challenge the classification of prokaryotes, which cannot be properly achieved in terms of a single gene or group of genes. Here, we studied individually the gene collection of the archaic microorganism Lokiarchaeum sp., suggested as an archaeal host close to the emergence of the eukaryotes. The network or rhizome of all Lokiarchaeum sp. genes revealed that the genomic repertoire is mainly composed of genes from archaeal (**36%) and bacterial origin (**28%), distantly followed by components of eukaryotic origin (**2%). Thirty-three percent of geneswere unique to this species (ORFans). Themosaicity of archaeawas also supported by studying Methanomassiliicoccus luminyensis, an archaea fromthe gut, inwhich 67%of the genomic repertoire arised fromarchaea and 22% from bacteria. Our results illustrate the intricate evolutionary relationships of the archaeal genome repertoire and highlight the rhizome-like processes of evolution in archaea, their mosaicity, and chimeric origin composed of different domains of life, questioning the reality of a tree of life. [ABSTRACT FROM AUTHOR]

RAG1 and RAG2 are essential subunits of the V(D)J recombinase required for the generation of the variability of antibodies and T cell receptors in jawed vertebrates. It was demonstrated that the amphioxus homologue of RAG1-RAG2 is encoded in an active transposon, belonging to the transposase DDE superfamily. The data provided support the possibility that the RAG transposon has been active through the deuterostome evolution and is still active in several lineages. The RAG transposon corresponds to several families present in deuterostomes. RAG1-RAG2 V(D)J recombinase evolved from one of them, partially due to the new ability of the transposon to interact with the cellular reparation machinery. Considering the fact that the RAG transposon survived millions of years in many different lineages, in multiple copies, and that DDE transposases evolved their association with proteins involved in repair mechanisms, we propose that the apparition of V(D)J recombination machinery could be a predictable genetic event. [ABSTRACT FROM AUTHOR]

With the inclusion of new members, understanding about evolutionary mechanisms and processes by which members of the proposed order, Megavirales, have evolved has become a key area of interest. The central role of gene acquisition has been shown in previous studies. However, the major drawback in gene acquisition studies is the focus on few MV families or putative families with large variation in their genetic structure. Thus, here we have tried to develop a methodology by which we can detect horizontal gene transfers (HGTs), taking into consideration orthologous groups of distantly related Megavirale families. Here, we report an automated workflow MimiLook, prepared as a Perl command line program, that deduces orthologous groups (OGs) from ORFomes of Megavirales and constructs phylogenetic trees by performing alignment generation, alignment editing and protein-protein BLAST (BLASTP) searching across the National Center for Biotechnology Information (NCBI) non-redundant (nr) protein sequence database. Finally, this tool detects statistically validated events of gene acquisitions with the help of the T-REX algorithm by comparing individual gene tree with NCBI species tree. In between the steps, the workflow decides about handling paralogs, filtering outputs, identifying Megavirale specific OGs, detection of HGTs, along with retrieval of information about those OGs that are monophyletic with organisms from cellular domains of life. By implementing MimiLook, we noticed that nine percent of Megavirale gene families (i.e., OGs) have been acquired by HGT, 80% OGs were Megaviralespecific and eight percent were found to be sharing common ancestry with members of cellular domains (Eukaryote, Bacteria, Archaea, Phages or other viruses) and three percent were ambivalent. The results are briefly discussed to emphasize methodology. Also, MimiLook is relevant for detecting evolutionary scenarios in other targeted phyla with user defined modifications. [ABSTRACT FROM AUTHOR]

Summary Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG , a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1 -like and RAG2 -like genes. We demonstrate that ProtoRAG was recently active in the lancelet germline and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular “living fossil” of the long-sought RAG transposon. [ABSTRACT FROM AUTHOR]

With more than 30,000 species, ray-finned fish represent approximately half of vertebrates. The evolution of ray-finned fish was impacted by several whole genome duplication (WGD) events including a teleost-specific WGD event (TGD) that occurred at the root of the teleost lineage about 350 million years ago (Mya) and more recent WGD events in salmonids, carps, suckers and others. In plants and animals, WGD events are associated with adaptive radiations and evolutionary innovations. WGD-spurred innovation may be especially relevant in the case of teleost fish, which colonized a wide diversity of habitats on earth, including many extreme environments. Fish biodiversity, the use of fish models for human medicine and ecological studies, and the importance of fish in human nutrition, fuel an important need for the characterization of gene expression repertoires and corresponding evolutionary histories of ray-finned fish genes. To this aim, we performed transcriptome analyses and developed the PhyloFish database to provide (i) de novo assembled gene repertoires in 23 different ray-finned fish species including two holosteans (i.e. a group that diverged from teleosts before TGD) and 21 teleosts (including six salmonids), and (ii) gene expression levels in ten different tissues and organs (and embryos for many) in the same species. This resource was generated using a common deep RNA sequencing protocol to obtain the most exhaustive gene repertoire possible in each species that allows between-species comparisons to study the evolution of gene expression in different lineages. The PhyloFish database described here can be accessed and searched using RNAbrowse, a simple and efficient solution to give access to RNA-seq de novo assembled transcripts. [ABSTRACT FROM AUTHOR]

The MHC is a large genetic region controlling Ag processing and recognition by T lymphocytes in vertebrates. Approximately 40% of its genes are implicated in innate or adaptive immunity. A putative proto-MHC exists in the chordate amphioxus and in the fruit fly, indicating that a core MHC region predated the emergence of the adaptive immune system in vertebrates. In this study, we identify a putative proto-MHC with archetypal markers in the most basal branch of Metazoans—the placozoan Trichoplax adhaerens, indicating that the proto-MHC is much older than previously believed—and present in the common ancestor of bilaterians (contains vertebrates) and placozoans. Our evidence for a T. adhaerens proto-MHC was based on macrosynteny and phylogenetic analyses revealing approximately one third of the multiple marker sets within the human MHC-related paralogy groups have unique counterparts in T. adhaerens, consistent with two successive whole genome duplications during early vertebrate evolution. A genetic ontologic analysis of the proto-MHC markers in T. adhaerens was consistent with its involvement in defense, showing proteins implicated in antiviral immunity, stress response, and ubiquitination/proteasome pathway. Proteasome genes psma, psmb, and psmd are present, whereas the typical markers of adaptive immunity, such as MHC class I and II, are absent. Our results suggest that the proto-MHC was involved in intracellular intrinsic immunity and provide insight into the primordial architecture and functional landscape of this region that later in evolution became associated with numerous genes critical for adaptive immunity in vertebrates. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium abscessus is an emerging opportunistic pathogen which diversity was acknowledged by the recent description of two subspecies accommodating M. abscessus, Mycobacterium bolletii and Mycobacterium massiliense isolates. Results: Here, genome analysis found 1'8 prophage regions in 47/48 M. abscessus genomes ranging from small prophage-like elements to complete prophages. A total of 20,304 viral and phage proteins clustered into 853 orthologous groups. Phylogenomic and phylogenetic analyses based on prophage region homology found three main clusters corresponding to M. abscessus, M. bolletii and M. massiliense. Analysing 135 annotated Tape Measure Proteins found thirteen clusters and four singletons, suggesting that at least 17 mycobacteriophages had infected M. abscessus during its evolution. The evolutionary history of phages differed from that of their mycobacterial hosts. In particular, 33 phage-related proteins have been horizontally transferred within M. abscessus genomes. They comprise of an integrase, specific mycobacteriophage proteins, hypothetical proteins and DNA replication and metabolism proteins. Gene exchanges, loss and gains which occurred in M. abscessus genomes have been driven by several mycobacteriophages. Conclusions: This analysis of phage-mycobacterium co-evolution suggests that mycobacteriophages are playing a key-role in the on-going diversification of M. abscessus. [ABSTRACT FROM AUTHOR]

Environmental metagenomic studies show that there is a “dark matter,” composed of sequences not linked to any known organism, as determined mainly using ribosomal DNA (rDNA) sequences, which therefore ignore giant viruses. DNA-dependent RNA polymerase (RNAP) genes are universal in microbes and conserved in giant viruses and may replace rDNA for identifying microbes. We found while reconstructing RNAP subunit 2 (RNAP2) phylogeny that a giant virus sequenced together with the genome of a large eukaryote, Hydra magnipapillata, has been overlooked. To explore the dark matter, we used viral RNAP2 and reconstructed putative ancestral RNAP2, which were significantly superior in detecting distant clades than current sequences, and we revealed two additional unknown mimiviruses, misclassified as an euryarchaeote and an oomycete plant pathogen, and detected unknown putative viral clades. We suggest using RNAP systematically to decipher the black matter and identify giant viruses. [ABSTRACT FROM PUBLISHER]

It is well known that horizontal gene transfer (HGT) is a major force in the evolution of prokaryotes. During the adaptation of a bacterial population to a new ecological niche, and particularly for intracellular bacteria, selective pressures are shifted and ecological niches reduced, resulting in a lower rate of genetic connectivity. HGT and positive selection are therefore two important evolutionary forces in microbial pathogens that drive adaptation to new hosts. In this study, we use genomic distance analyses, phylogenomic networks, tree topology comparisons, and Bayesian inference methods to investigate to what extent HGT has occurred during the evolution of the genus Rickettsia, the effect of the use of different genomic regions in estimating reticulate evolution and HGT events, and the link of these to host range. We show that ecological specialization restricts recombination occurrence in Rickettsia, but other evolutionary processes and genome architecture are also important for the occurrence of HGT. We found that recombination, genomic rearrangements, and genome conservation all show evidence of network-like evolution at whole-genome scale. We show that reticulation occurred mainly, but not only, during the early Rickettsia radiation, and that core proteome genes of every major functional category have experienced reticulated evolution and possibly HGT. Overall, the evolution of Rickettsia bacteria has been tree-like, with evidence of HGT and reticulated evolution for around 10–25% of the core Rickettsia genome. We present evidence of extensive recombination/incomplete lineage sorting (ILS) during the radiation of the genus, probably linked with the emergence of intracellularity in a wide range of hosts. [ABSTRACT FROM AUTHOR]