Biology subjects

Pontarotti, P.

Publications and source records attributed to Pontarotti, P..

10 recordsLinked to original sources

bioRxiv2024

Intrinsically linked lineage-specificity of transposable elements and lncRNAs reshapes transcriptional regulation species- and tissue-specifically

Unlike protein-coding genes, many mammalian lncRNAs are lineage-specific (LS), but which human and mouse reference lncRNAs are lineage-specific, how they are generated, and whether their regulatory elements are lineage-specific remain unclear. To resolve their origins, properties, and impacts, we systematically classified primate-, simian-, rodent-, human-, and mouse-specific lncRNAs in GENCODE-annotated human and mouse genomes using structure-aware covariance modeling. We predicted their DNA-binding domains (DBDs) and genomic binding sites (DBSs) and traced the origins of embedded transposable elements (TEs). LS TEs contribute to over 84% (human) and 98% (mouse) of LS lncRNAs, 61% and 95% of their DBDs, and 46% and 73% of their DBSs. Analyses of multi-omics data and a developmental process suggest that LS TE-linked lineage-specificity substantially rewires transcriptional regulation and that many evolutionary novelties may be structurally predisposed. These findings bridge the gap between human diseases and mouse models, providing valuable resources for identifying human-specific therapeutic lncRNA targets.

genomics↗

bioRxiv2024

Pre-Columbian treponemes clarify worldwide spread of treponematosis

Syphilis dramatically hit Europe at the end of the fifteen century before spreading to other continents. Yet the origin of the sudden pandemic in the Old World remains debated, in particular because the leading Columbus hypothesis of a New World origin of historical syphilis in Europe lacks paleomicrobiological confirmation. Here we screened a worldwide set of >1,700 ancient humans and identified ancient Treponema pallidum strains in two pre-Columbian child sacrifices from Tlatelolco, Mexico. Over 12,000 Treponema-specific reads were recovered to define a novel Treponema pallidum ancient population: Treponema pallidum str. tlatelolcoensis. Phylogenetics show that this population displays ancestral features but also bears the genetic building blocks of disease-causing modern Treponema pallidum subspecies, hence demonstrating how pre-Colombian Americas were the source of worldwide spread of treponematosis.

microbiology↗

bioRxiv2023

Insights into RAG evolution from the identification of "missing link" family A RAGL transposons

A series of "molecular domestication" events are thought to have converted an invertebrate RAG-like (RAGL) transposase into the RAG1-RAG2 (RAG) recombinase, a critical enzyme for adaptive immunity in jawed vertebrates. The timing and order of these events is not well understood, in part because of a dearth of information regarding the invertebrate RAGL-A transposon family. In contrast to the abundant and divergent RAGL-B transposon family, RAGL-A most closely resembles RAG and is represented by a single orphan RAG1-like (RAG1L) gene in the genome of the hemichordate Ptychodera flava (PflRAG1L-A). Here, we provide evidence for the existence of complete RAGL-A transposons in the genomes of P. flava and several echinoderms. The predicted RAG1L-A and RAG2L-A proteins encoded by these transposons intermingle sequence features of jawed vertebrate RAG and RAGL-B transposases, leading to a prediction of DNA binding, catalytic, and transposition activities that are a hybrid of RAG and RAGL-B. Similarly, the terminal inverted repeats (TIRs) of the RAGL-A transposons combine features of both RAGL-B transposon TIRs and RAG recombination signal sequences. Unlike all previously described RAG2L proteins, PflRAG2L-A and echinoderm RAG2L-A contain an acidic hinge region, which we demonstrate is capable of efficiently inhibiting RAG-mediated transposition. Our findings provide evidence for a critical intermediate in RAG evolution and argue that certain adaptations thought to be specific to jawed vertebrates (e.g., the RAG2 acidic hinge) actually arose in invertebrates, thereby focusing attention on other adaptations as the pivotal steps in the completion of RAG domestication in jawed vertebrates.

evolutionary biology↗

bioRxiv2023

Role of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic

RNA viruses, including SARS-CoV-2, evolve by mutation acquisition, or by hybridization between viral genomes. The SARS-CoV-2 pandemic provided an exceptional opportunity to analyze the mutations that appeared over a three-year period. In this study, we analysed the type of mutations and their epidemic consequences on the thousands of genomes produced in our laboratory. These were obtained by next-generation sequencing from respiratory samples performed for genomic surveillance. The frequencies of mutations were calculated using Nextclade, Microsoft Excel, and an in-house Python script. In total, 61,397 genomes matching 483 Pangolin lineages were analyzed; 22,225 nucleotide mutations were identified, and of them 220 (1.0%) were each at the root of at least 836 genomes, a frequency threshold classifying mutations as "hyperfertile". Two of these seeded the pandemic in Europe, namely a mutation in the RNA-dependent RNA polymerase associated with an increased mutation rate (P323L) and one in the spike protein (D614G), which plays a particular role in virus fitness. Most of these 220 "hyperfertile" mutations occurred in areas not predicted to be associated with increased virulence. Their number was 8{+/-}6 (0-22) per 1,000 nucleotides on average per gene. They were 3.7 times more frequent in accessory than informational genes (14 versus 4; p= 0.0037). Particularly, they were 4.1 times more frequent in ORF8 than in the gene encoding RNA polymerase. Interestingly, stop codons were present in 97 positions, almost only in six accessory genes including ORF7a (25 per 100 codons) and ORF8 (21). Furthermore, 1,661 mutations (16.3%) were associated with a lower number of "offspring" (50-835) and classified as "fertile". In conclusion, except for two initial mutations that could predict a change in the dynamics of the epidemic (mutation rate and change in the virus attachment site), most of the "hyperfertile" mutations did not predict the emergence of a new epidemic form. Significantly, some mutations were in non-coding areas and some consisted of stop codons, indicating that some genes (particularly ORF7a and ORF8) were rather "non-virulence genes" at a given stage of the epidemic, which is an unusual concept for viruses.

microbiology↗

bioRxiv2022

Parallel evolution of amphioxus and vertebrate small-scale gene duplications

BackgroundAmphioxus are non-vertebrate chordates characterized by a slow morphological and molecular evolution. They share the basic chordate body-plan and genome organization with vertebrates but lack their 2R whole-genome duplications and their developmental complexity. For these reasons, amphioxus are frequently used as an outgroup to study vertebrate genome evolution and Evo-Devo. Aside from whole-genome duplications, genes continuously duplicate on a smaller scale. Small-scale duplicated genes can be found in both amphioxus and vertebrate genomes, while only the vertebrate genomes have duplicated genes product of their 2R whole-genome duplications. Here, we explore the history of small-scale gene duplications in the amphioxus lineage and compare it to small- and large-scale gene duplication history in vertebrates. ResultsWe present a study of the European amphioxus (Branchiostoma lanceolatum) gene duplications thanks to a new, high-quality genome reference. We find that, despite its overall slow molecular evolution, the amphioxus lineage has had a history of small-scale duplications similar to the one observed in vertebrates. We find parallel gene duplication profiles between amphioxus and vertebrates, and conserved functional constraints in gene duplication. Moreover, amphioxus gene duplicates show levels of expression and patterns of functional specialization similar to the ones observed in vertebrate duplicated genes. We also find strong conservation of gene synteny between two distant amphioxus species, B. lanceolatum and B. floridae, with two major chromosomal rearrangements. ConclusionsIn contrast to their slower molecular and morphological evolution, amphioxus small-scale gene duplication history resembles that of the vertebrate lineage both in quantitative and in functional terms.

evolutionary biology↗

bioRxiv2019

A metallo-beta-lactamase with both beta-lactamase and ribonuclease activity is linked with traduction in giant viruses

Enzymatic proteins with a metallo-beta-lactamase (MBL) fold have been essentially studied in bacteria for their activity on beta-lactam antibiotics. However, the MBL fold is ancient and highly conserved, and these proteins are capable of cleaving a broad range of substrates. It has recently been shown that MBLs are present in a wide array of cellular organisms, including eukaryotes and archaea. We show here that Tupanvirus deep ocean, a giant virus, also encodes a protein with a MBL fold. Phylogeny showed its clustering with transfer ribonucleases (RNases) and the presence of orthologs in other giant viruses, mainly those harboring the largest sets of translation components. In addition, it suggests an ancient origin for these genes and a transfer between giant viruses and Acanthamoeba spp., a host of many giant viruses. Biologically, after its expression in Escherichia coli, the tupanvirus protein was found to hydrolyse nitrocefin, a chromogenic beta-lactam. We also observed an hydrolysis of penicillin G (10 g/mL) and detected the metabolite of penicillin G hydrolysis, benzylpenilloic acid. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, we tested the degradation of single-stranded DNA, double-stranded DNA, and RNAs, and observed a strong activity on RNAs from seven bacteria with G+C varying from 42% to 67%, and from Acanthamoeba castellanii, the tupanvirus host. This was not inhibited by sulbactam or ceftriaxone. RNase activity was estimated to be 0.45{+/-}0.15 mU/mg using a fluorescence-based assay. Our results still broaden the range of hosts of MBL fold proteins and demonstrate that such protein can have dual beta-lactamase/nuclease activities. We suggest that they should be annotated according to this finding to avoid further confusion.

microbiology↗

bioRxiv2019

Paradoxical β-lactamase activity of archaeal encoding enzymes

{beta}-lactams targeting the bacterial cell wall are not active on archaea. Here, we figure out that annotation of genes as {beta}-lactamase in Archeae on the basis of homologous genes, initially annotated {beta}-lactamases, is a remnant of the identification of the original activities of this group of enzymes, which in fact, have multiple functions including nuclease, ribonuclease, {beta}-lactamase, or glyoxalase; which may specialized over time. We expressed a class B {beta}-lactamase enzyme from Methanosarcina barkeri that digest penicillin G. Moreover, while a weak glyoxalase activity was detected, a significant ribonuclease activity on bacterial and synthetic RNAs was demonstrated. The {beta}-lactamase activity was inhibited by a {beta}-lactamase inhibitor (sulbactam), but its RNAse activity was not. This gene appears to has been transferred to the Flavobacteriaceae group including Elizabethkingia genus in which the expressed gene shows a more specialized activity toward resistance to tienanmicin but no glyoxalase activity. The expressed class C-like {beta}-lactamase gene, also from Methanosarcina sp., shows also hydrolysis activity and was more closely related to DD-peptidase enzymes than known bacterial class C {beta}-lactamases. Our findings highlight the requalification needness of annotated enzymes as {beta}-lactamases and the specification overtime of multipotent enzymes in different ways in Archaea and bacteria.

microbiology↗

bioRxiv2018

Gene expression plasticity and frontloading promote thermotolerance in Pocilloporid corals

Ecosystems worldwide are suffering from climate change. Coral reef ecosystems are globally threatened by increasing sea surface temperatures. However, gene expression plasticity provides the potential for organisms to respond rapidly and effectively to environmental changes, and would be favored in variable environments. In this study, we investigated the thermal stress response in Pocillopora coral colonies from two contrasting environments by exposing them to heat stress. We compared the physiological state, bacterial and Symbionaceae communities (using 16S and ITS2 metabarcoding), and gene expression levels (using RNA-Seq) between control conditions and heat stress (the temperature just below the first signs of compromised health). Colonies from both thermal regimes remained apparently normal and presented open and colored polyps during heat stress, with no change in bacterial and Symbionaceae community composition. In contrast, they differed in their transcriptomic responses. The colonies from Oman displayed a more plastic transcriptome, but some genes had a higher basal expression level (frontloading) compared to the less thermotolerant colonies from New Caledonia. In terms of biological functions, we observed an increase in the expression of stress response genes (including induction of tumor necrosis factor receptors, heat shock proteins, and detoxification of reactive oxygen species), together with a decrease in the expression of genes involved in morpho-anatomical functions. Gene regulation (transcription factors, mobile elements, histone modifications and DNA methylation) appeared to be overrepresented in the Oman colonies, indicating possible epigenetic regulation. These results show that transcriptomic plasticity and frontloading can be co-occurring processes in corals confronted to highly variable thermal regimes.

evolutionary biology↗

bioRxiv2018

Separate the wheat from the chaff: genomic analysis of local adaptation in the red coral Corallium rubrum

Genomic data allow an in-depth and renewed study of local adaptation. The red coral (Corallium rubrum, Cnidaria) is a highly genetically structured species and a promising model for the study of adaptive processes along an environmental gradient. Here, we used RAD-Sequencing in order to study the vertical genetic structure of this species and to search for signals of local adaptation to depth and thermal regime in the red coral. Previous studies have shown different thermotolerance levels according to depth in this species which could correspond to genetic or environmental differences. We designed a sampling scheme with six pairs of shallow vs deep populations distributed in three geographical regions as replicates. Our results showed significant differentiation among locations and among sites separated by around 20 m depth. The tests of association between genetics and environment allowed the identification of candidate loci under selection but with a potentially high rate of false positive. We discuss the methodological obstacles and biases encountered for the detection of selected loci in such a strongly genetically structured species. On this basis, we also discuss the significance of the candidate loci for local adaptation detected in each geographical region and the evolution of red coral populations along environmental gradients.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC=\"FIGDIR/small/306456_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (110K):\norg.highwire.dtl.DTLVardef@11d6129org.highwire.dtl.DTLVardef@1d604c3org.highwire.dtl.DTLVardef@1d2bef2org.highwire.dtl.DTLVardef@f64160_HPS_FORMAT_FIGEXP M_FIG A colony of red coral, Corallium rubrum, near Marseille. Photo: F. Zuberer / OSU Pytheas / CNRS\n\nC_FIG

evolutionary biology↗

bioRxiv2017

Detecting Molecular Basis Of Phenotypic Convergence

Convergence is the process by which several species independently evolve similar traits. This evolutionary process is not only strongly related to fundamental questions such as the predictability of evolution and the role of adaptation, its study also may provide new insights about genes involved in the convergent character. We focus on this latter question and aim to detect molecular basis of a given phenotypic convergence. After pointing out a number of concerns about detection methods based on ancestral reconstruction, we propose a novel approach combining an original measure of the extent to which a site supports a phenotypic convergence, with a statistical framework for selecting genes from the measure of their sites. First, our measure of \"convergence level\" outperforms two previous ones in distinguishing simulated convergent sites from non-convergent ones. Second, by applying our detection approach to the well-studied case of convergent echolocation between dolphins and bats, we identified a set of genes which is very significantly annotated with audition-related GO-terms. This result constitutes an indirect evidence that genes involved in a phenotypic convergence can be identified with a genome-wide approach, a point which was highly debated, notably in the echolocation case (the latest articles published on this topic were quite pessimistic). Our approach opens the way to systematic studies of numerous examples of convergent evolution in order to link (convergent) phenotype to genotype.

evolutionary biology↗