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Search Results: 1 - 10 of 401503 matches for " Claudine Médigue "
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Distinct co-evolution patterns of genes associated to DNA polymerase III DnaE and PolC
Stefan Engelen, David Vallenet, Claudine Médigue, Antoine Danchin
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-69
Abstract: Extending previous in silico heuristics for the analysis of gene co-evolution, we analyzed the function of genes clustering with dnaE and polC. Clusters were highly informative. DnaE co-evolves with the ribosome, the transcription machinery, the core of intermediary metabolism enzymes. It is also connected to the energy-saving enzyme necessary for RNA degradation, polynucleotide phosphorylase. Most of the proteins of this co-evolving set belong to the persistent set in bacterial proteomes, that is fairly ubiquitously distributed. In contrast, PolC co-evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade, suggesting at least two origins for the degradosome.DNA replication involves two machineries, DnaE and PolC. DnaE co-evolves with the core functions of bacterial life. In contrast PolC co-evolves with a set of RNA degradation enzymes that does not derive from the degradosome identified in gamma-Proteobacteria. This suggests that at least two independent RNA degradation pathways existed in the progenote community at the end of the RNA genome world.Future developments of Synthetic Biology require that patterns of gene organization in genomes are carefully taken into account [1]. Following the pioneering work of Sueoka [2], Lobry and co-workers identified a replication-linked bias in the nucleotide distribution in bacterial chromosomes. Subsequently, a bias in favor of genes transcribed in the same direction as that of the movement of the replication fork was observed in most bacterial genomes [3,4]. The bias was correlated with the presence in the genome of a single origin of replication. Taken together, these observations led to the construction of algorithms meant to identify in silico the origins of replication [5]. The cause of the bias has been a matter of speculation until it was observed that Firmicutes displayed the strongest bias [6,7] reaching 87% in organisms such as Thermoanaerobacter tengcongensis [8]. A first hypothe
Re-annotation of genome microbial CoDing-Sequences: finding new genes and inaccurately annotated genes
Stéphanie Bocs, Antoine Danchin, Claudine Médigue
BMC Bioinformatics , 2002, DOI: 10.1186/1471-2105-3-5
Abstract: We have developed a new program that automatically identifies biologically significant candidate genes in a bacterial genome. Twenty-six complete prokaryotic genomes were analyzed using this tool, and the accuracy of gene finding was assessed by comparison with existing annotations. This analysis revealed that, despite the enormous effort of genome program annotators, a small but not negligible number of genes annotated within the framework of sequencing projects are likely to be partially inaccurate or plainly wrong. Moreover, the analysis of several putative new genes shows that, as expected, many short genes have escaped annotation. In most cases, these new genes revealed frameshifts that could be either artifacts or genuine frameshifts. Some entirely unexpected new genes have also been identified. This allowed us to get a more complete picture of prokaryotic genomes. The results of this procedure are progressively integrated into the SWISS-PROT reference databank.The results described in the present study show that our procedure is very satisfactory in terms of gene finding accuracy. Except in few cases, discrepancies between our results and annotations provided by individual authors can be accounted for by the nature of each annotation process or by specific characteristics of some genomes. This stresses that close cooperation between scientists, regular update and curation of the findings in databases are clearly required to reduce the level of errors in genome annotation (and hence in reducing the unfortunate spreading of errors through centralized data libraries).The main goal of large-scale genome sequencing projects is to obtain new insights into physiological and biological processes underlying the very organization of life. An essential step in this quest is gene identification, with subsequent functional annotation of the corresponding gene products. Gene recognition in bacteria is far from being always straightforward, despite the fact that bacterial g
Small variable segments constitute a major type of diversity of bacterial genomes at the species level
Fabrice Touzain, Erick Denamur, Claudine Médigue, Valérie Barbe, Meriem El Karoui, Marie-Agnès Petit
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-4-r45
Abstract: We performed a systematic analysis of the variable segments detected by multiple whole genome alignments at the DNA level on three species for which the greatest number of genomes have been sequenced: Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes. Among the numerous sites of variability, 62 to 73% were loci of microdiversity, many of which were located within genes. They contribute to phenotypic variations, as 3 to 6% of all genes harbor microdiversity, and 1 to 9% of total genes are located downstream from a microdiversity locus. Microdiversity loci are particularly abundant in genes encoding membrane proteins. In-depth analysis of the E. coli alignments shows that most of the diversity does not correspond to known mobile or repeated elements, and it is likely that they were generated by illegitimate recombination. An intriguing class of microdiversity includes small blocks of highly diverged sequences, whose origin is discussed.This analysis uncovers the importance of this small-sized genome diversity, which we expect to be present in a wide range of bacteria, and possibly also in many eukaryotic genomes.The availability of bacterial genome sequences for closely related strains within a species and software dedicated to multiple genome alignments allow for a novel perspective of bacterial genetic diversity [1-3]. Use of these aligners has led to the notion that bacterial species share a DNA backbone common to all strains interrupted by variable segments (VSs) that are specific to a subset of the aligned strains [4-6]. The most studied category of VSs are genomic islands, which are defined by Vernikos and Parkhill as horizontally acquired mobile elements of limited phylogenetic distribution [7]. These islands are of a large size (30 to 100 kb), and often encode genes critical for pathogenesis [8]. Their integration into genomes presumably occurs by site-specific recombination. Genomic islands may then diffuse from strain to strain by homologou
Horizontal gene transfer may explain variation in θs
Rohan Maddamsetti,Philip J. Hatcher,Stéphane Cruveiller,Claudine Médigue,Jeffrey E. Barrick,Richard E. Lenski
Quantitative Biology , 2012,
Abstract: Martincorena et al. estimated synonymous diversity ({\theta}s = 2N{\mu}) across 2,930 orthologous gene alignments from 34 Escherichia coli genomes, and found substantial variation among genes in the density of synonymous polymorphisms. They argue that this pattern reflects variation in the mutation rate per nucleotide ({\mu}) among genes. However, the effective population size (N) is not necessarily constant across the genome. In particular, different genes may have different histories of horizontal gene transfer (HGT), whereas Martincorena et al. used a model with random recombination to calculate {\theta}s. They did filter alignments in an effort to minimize the effects of HGT, but we doubt that any procedure can completely eliminate HGT among closely related genomes, such as E. coli living in the complex gut community. Here we show that there is no significant variation among genes in rates of synonymous substitutions in a long-term evolution experiment with E. coli and that the per-gene rates are not correlated with {\theta}s estimates from genome comparisons. However, there is a significant association between {\theta}s and HGT events. Together, these findings imply that {\theta}s variation reflects different histories of HGT, not local optimization of mutation rates to reduce the risk of deleterious mutations as proposed by Martincorena et al.
Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella
Philipp Engel,Walter Salzburger,Marius Liesch,Chao-Chin Chang,Soichi Maruyama,Christa Lanz,Alexandra Calteau,Aurélie Lajus,Claudine Médigue,Stephan C. Schuster,Christoph Dehio
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1001296
Abstract: Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens. Furthermore, our study highlights the remarkable evolvability of T4SSs and their effector proteins, explaining their broad application in bacterial interactions with the environment.
NeMeSys: a biological resource for narrowing the gap between sequence and function in the human pathogen Neisseria meningitidis
Christophe Rusniok, David Vallenet, Stéphanie Floquet, Helen Ewles, Coralie Mouzé-Soulama, Daniel Brown, Aurélie Lajus, Carmen Buchrieser, Claudine Médigue, Philippe Glaser, Vladimir Pelicic
Genome Biology , 2009, DOI: 10.1186/gb-2009-10-10-r110
Abstract: By determining and manually annotating the complete genome sequence of a serogroup C clinical isolate of N. meningitidis (strain 8013) and assembling a library of defined mutants in up to 60% of its non-essential genes, we have created NeMeSys, a biological resource for Neisseria meningitidis systematic functional analysis. To further enhance the versatility of this toolbox, we have manually (re)annotated eight publicly available Neisseria genome sequences and stored all these data in a publicly accessible online database. The potential of NeMeSys for narrowing the gap between sequence and function is illustrated in several ways, notably by performing a functional genomics analysis of the biogenesis of type IV pili, one of the most widespread virulence factors in bacteria, and by identifying through comparative genomics a complete biochemical pathway (for sulfur metabolism) that may potentially be important for nasopharyngeal colonization.By improving our capacity to understand gene function in an important human pathogen, NeMeSys is expected to contribute to the ongoing efforts aimed at understanding a prokaryotic cell comprehensively and eventually to the design of new therapies.By revealing complete repertoires of genes, genome sequences provide the key to a better and eventually global understanding of the biology of living organisms. It is widely accepted that this will have important consequences on human health and economics by leading to the rational design of novel therapies against pathogens infecting humans, livestock or crops [1]. For example, identifying genes essential for cell viability or pathogenesis would uncover targets for new antibiotics or drugs that selectively interfer with virulence mechanisms of pathogenic species, respectively. The major obstacle to this is the fact that hundreds of predicted coding sequences (CDSs) in every genome remain uncharacterized. Unraveling gene function on such a large scale requires suitable biological resources
Comparative Genomics of Aeschynomene Symbionts: Insights into the Ecological Lifestyle of Nod-Independent Photosynthetic Bradyrhizobia
Damien Mornico,Lucie Miché,Gilles Béna,Nico Nouwen,André Verméglio,David Vallenet,Alexander A.T. Smith,Eric Giraud,Claudine Médigue,Lionel Moulin
Genes , 2012, DOI: 10.3390/genes3010035
Abstract: Tropical aquatic species of the legume genus Aeschynomene are stem- and root-nodulated by bradyrhizobia strains that exhibit atypical features such as photosynthetic capacities or the use of a nod gene-dependent (ND) or a nod gene-independent (NI) pathway to enter into symbiosis with legumes. In this study we used a comparative genomics approach on nine Aeschynomene symbionts representative of their phylogenetic diversity. We produced draft genomes of bradyrhizobial strains representing different phenotypes: five NI photosynthetic strains (STM3809, ORS375, STM3847, STM4509 and STM4523) in addition to the previously sequenced ORS278 and BTAi1 genomes, one photosynthetic strain ORS285 hosting both ND and NI symbiotic systems, and one NI non-photosynthetic strain (STM3843). Comparative genomics allowed us to infer the core, pan and dispensable genomes of Aeschynomene bradyrhizobia, and to detect specific genes and their location in Genomic Islands (GI). Specific gene sets linked to photosynthetic and NI/ND abilities were identified, and are currently being studied in functional analyses.
Experimental Evolution of a Plant Pathogen into a Legume Symbiont
Marta Marchetti,Delphine Capela,Michelle Glew,Stéphane Cruveiller,Béatrice Chane-Woon-Ming,Carine Gris,Ton Timmers,Véréna Poinsot,Luz B. Gilbert,Philipp Heeb,Claudine Médigue,Jacques Batut,Catherine Masson-Boivin
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000280
Abstract: Rhizobia are phylogenetically disparate α- and β-proteobacteria that have achieved the environmentally essential function of fixing atmospheric nitrogen in symbiosis with legumes. Ample evidence indicates that horizontal transfer of symbiotic plasmids/islands has played a crucial role in rhizobia evolution. However, adaptive mechanisms that allow the recipient genomes to express symbiotic traits are unknown. Here, we report on the experimental evolution of a pathogenic Ralstonia solanacearum chimera carrying the symbiotic plasmid of the rhizobium Cupriavidus taiwanensis into Mimosa nodulating and infecting symbionts. Two types of adaptive mutations in the hrpG-controlled virulence pathway of R. solanacearum were identified that are crucial for the transition from pathogenicity towards mutualism. Inactivation of the hrcV structural gene of the type III secretion system allowed nodulation and early infection to take place, whereas inactivation of the master virulence regulator hrpG allowed intracellular infection of nodule cells. Our findings predict that natural selection of adaptive changes in the legume environment following horizontal transfer has been a major driving force in rhizobia evolution and diversification and show the potential of experimental evolution to decipher the mechanisms leading to symbiosis.
Growth of Yersinia pseudotuberculosis in human plasma: impacts on virulence and metabolic gene expression
Marie-Laure Rosso, Sylvie Chauvaux, Rodrigue Dessein, Caroline Laurans, Lionel Frangeul, Céline Lacroix, Angèle Schiavo, Marie-Agnès Dillies, Jeannine Foulon, Jean-Yves Coppée, Claudine Médigue, Elisabeth Carniel, Michel Simonet, Micha?l Marceau
BMC Microbiology , 2008, DOI: 10.1186/1471-2180-8-211
Abstract: To gain insight into the metabolic pathways and virulence factors expressed by the bacterium at the blood stage of pseudotuberculosis, we compared the overall gene transcription patterns (the transcriptome) of bacterial cells cultured in either human plasma or Luria-Bertani medium. The most marked plasma-triggered metabolic consequence in Y. pseudotuberculosis was the switch to high glucose consumption, which is reminiscent of the acetogenic pathway (known as "glucose overflow") in Escherichia coli. However, upregulation of the glyoxylate shunt enzymes suggests that (in contrast to E. coli) acetate may be further metabolized in Y. pseudotuberculosis. Our data also indicate that the bloodstream environment can regulate major virulence genes (positively or negatively); the yadA adhesin gene and most of the transcriptional units of the pYV-encoded type III secretion apparatus were found to be upregulated, whereas transcription of the pH6 antigen locus was strongly repressed.Our results suggest that plasma growth of Y. pseudotuberculosis is responsible for major transcriptional regulatory events and prompts key metabolic reorientations within the bacterium, which may in turn have an impact on virulence.The Gram-negative bacterium Y. pseudotuberculosis is a human enteropathogen which is able to cross the intestinal mucosa through the M cells in Peyer's patches and thus infect the underlying tissues (causing ileitis and mesenteric lymphadenitis). However, in elderly or debilitated individuals (those suffering from malignancies, immunodeficiencies, chronic liver diseases or diabetes mellitus, for example), the organism frequently gains access to the bloodstream and can cause an often fatal septicemia [1,2]. Known Y. pseudotuberculosis virulence genes are transcriptionally regulated by temperature – most probably in order to adapt to the bacterium's life cycle outside and inside the host. Regulation by the omnipresent thermal stimulus can be modulated (via a wide range of m
Genomes of three tomato pathogens within the Ralstonia solanacearum species complex reveal significant evolutionary divergence
Beno?t Remenant, Bénédicte Coupat-Goutaland, Alice Guidot, Gilles Cellier, Emmanuel Wicker, Caitilyn Allen, Mark Fegan, Olivier Pruvost, Mounira Elbaz, Alexandra Calteau, Gregory Salvignol, Damien Mornico, Sophie Mangenot, Valérie Barbe, Claudine Médigue, Philippe Prior
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-379
Abstract: The genomes of three tomato bacterial wilt pathogens, CFBP2957 (phy. IIA), CMR15 (phy. III) and PSI07 (phy. IV) were sequenced and manually annotated. These genomes were compared with those of three previously sequenced R. solanacearum strains: GMI1000 (tomato, phy. I), IPO1609 (potato, phy. IIB), and Molk2 (banana, phy. IIB). The major genomic features (size, G+C content, number of genes) were conserved across all of the six sequenced strains. Despite relatively high genetic distances (calculated from average nucleotide identity) and many genomic rearrangements, more than 60% of the genes of the megaplasmid and 70% of those on the chromosome are syntenic. The three new genomic sequences revealed the presence of several previously unknown traits, probably acquired by horizontal transfers, within the genomes of R. solanacearum, including a type IV secretion system, a rhi-type anti-mitotic toxin and two small plasmids. Genes involved in virulence appear to be evolving at a faster rate than the genome as a whole.Comparative analysis of genome sequences and gene content confirmed the differentiation of R. solanacearum species complex strains into four phylotypes. Genetic distances between strains, in conjunction with CGH analysis of a larger set of strains, revealed differences great enough to consider reclassification of the R. solanacearum species complex into three species. The data are still too fragmentary to link genomic classification and phenotypes, but these new genome sequences identify a pan-genome more representative of the diversity in the R. solanancearum species complex.The rapidly accumulating complete genomes in databases provide unique opportunities to study relationships among organisms. Since DNA sequences are conserved between closely related organisms, comparative genomic analyses are a powerful tool for understanding the complex evolutionary events in specific phylogenetic lineages.R. solanacearum, formerly known as Pseudomonas solanacearum and Bu
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