Nucleotide, gene and genome evolution : a score to bind them all

National audienceLe document est un résumé étend

Reconstruction of an ancestral Yersinia pestis genome and comparison with an ancient sequence

International audienceBackground: We propose the computational reconstruction of a whole bacterial ancestral genome at the nucleotide scale, and its validation by a sequence of ancient DNA. This rare possibility is offered by an ancient sequence of the late middle ages plague agent. It has been hypothesized to be ancestral to extant Yersinia pestis strains based on the pattern of nucleotide substitutions. But the dynamics of indels, duplications, insertion sequences and rearrangements has impacted all genomes much more than the substitution process, which makes the ancestral reconstruction task challenging. Results: We use a set of gene families from 13 Yersinia species, construct reconciled phylogenies for all of them, and determine gene orders in ancestral species. Gene trees integrate information from the sequence, the species tree and gene order. We reconstruct ancestral sequences for ancestral genic and intergenic regions, providing nearly a complete genome sequence for the ancestor, containing a chromosome and three plasmids. Conclusion: The comparison of the ancestral and ancient sequences provides a unique opportunity to assess the quality of ancestral genome reconstruction methods. But the quality of the sequencing and assembly of the ancient sequence can also be questioned by this comparison

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection

Phylogénie des dépendances et dépendances des phylogénies dans les gènes et les génomes

Molecular evolution, based on the study of sequencing data, established itself as a fundamental approach in the study of the history of living organisms (noticeably through the inference of phylogenetic trees). Classical molecular evolution methods rely on the decomposition of genomes into entities that are supposed independent: genes. However we know that genes do not evolve independently: their potential biological function lead them to be influenced by (and influence) the evolution of other genes. Moreover, their position along chromosomes imply that they share events of structural mutations (duplication, loss of a chromosome fragment) with neighbouring genes. Similarly, a gene individual history inscribes itself in the history of the species that bears it. I show that not taking into account this inter-dependency relationships (co- evolutionary relationships) during the inference of gene trees results in an overesti- mation of the differences between gene trees as well as between gene tree and species tree. Modelling efforts these last year have allowed the integration of gene and species co-evolution information to the reconstruction of gene trees. Besides, researchers have proposed models describing the evolution of the relationships linking genes, but without integration of this information in the tree building process. My works aim to combine these advances in a method that modify gene trees according to a criterion that integrates sequence information and information coming from co-evolution relationships. This method, applied to mammals and fungi, leads to gene histories that are more congruent (simpler adjacency histories, longer events of loss or transfer, ...)L'évolution moléculaire, basée sur l'étude des données de séquençage, s'est imposée comme une approche majeure pour l'étude de l'Histoire des organismes vivants (notamment à travers les arbres phylogénétiques). Ses méthodes classiques reposent sur un découpage des génomes en entités supposées indépendantes : les gènes. Or, les gènes n'évoluent pas indépendamment : au sein de l'histoire des espèces qui le portent, l'histoire d'un gène s'inscrit. En outre, leur position le long des chromosomes fait qu'ils partagent des événements de mutations structurales (duplications, pertes de fragments chromosomiques) avec les gènes proches. Enfin, leur potentielle fonction biologique les amène à être influencés par (et à influencer en retour) l'évolution d'autres gènes. Je montre que ne pas prendre en compte ces relations d'inter-dépendances évolutives (de coévolution) lors de l'inférence d'arbres de gènes résulte en une suresti mation des différences entre les arbres des différents gènes ainsi qu'entre les arbres des gènes et l'arbre des espèces. Des modèles permettent déjà d'intégrer la coévolution des gènes avec les espèces à la reconstruction des arbres de gènes. Par ailleurs, on connaît des modèles décrivant l'évolution des relations entre gènes, néanmoins sans intégrer ces informations à la reconstruction des arbres de gènes. Je reprends ces avancées et les combine au sein d'une méthode qui modifie les arbres de gènes selon un critère qui prend en compte les séquences ainsi que des relations de coévolution avec les espèces et d'autres gènes. Cette méthode, appliquée à des mammifères et des champignons, permet de produire des histoires de gènes cohérentes entre elle

Phylogénie des dépendances et dépendances des phylogénies dans les gènes et les génomes

Molecular evolution, based on the study of sequencing data, established itself as a fundamental approach in the study of the history of living organisms (noticeably through the inference of phylogenetic trees). Classical molecular evolution methods rely on the decomposition of genomes into entities that are supposed independent: genes. However we know that genes do not evolve independently: their potential biological function lead them to be influenced by (and influence) the evolution of other genes. Moreover, their position along chromosomes imply that they share events of structural mutations (duplication, loss of a chromosome fragment) with neighbouring genes. Similarly, a gene individual history inscribes itself in the history of the species that bears it. I show that not taking into account this inter-dependency relationships (co- evolutionary relationships) during the inference of gene trees results in an overesti- mation of the differences between gene trees as well as between gene tree and species tree. Modelling efforts these last year have allowed the integration of gene and species co-evolution information to the reconstruction of gene trees. Besides, researchers have proposed models describing the evolution of the relationships linking genes, but without integration of this information in the tree building process. My works aim to combine these advances in a method that modify gene trees according to a criterion that integrates sequence information and information coming from co-evolution relationships. This method, applied to mammals and fungi, leads to gene histories that are more congruent (simpler adjacency histories, longer events of loss or transfer, ...)L'évolution moléculaire, basée sur l'étude des données de séquençage, s'est imposée comme une approche majeure pour l'étude de l'Histoire des organismes vivants (notamment à travers les arbres phylogénétiques). Ses méthodes classiques reposent sur un découpage des génomes en entités supposées indépendantes : les gènes. Or, les gènes n'évoluent pas indépendamment : au sein de l'histoire des espèces qui le portent, l'histoire d'un gène s'inscrit. En outre, leur position le long des chromosomes fait qu'ils partagent des événements de mutations structurales (duplications, pertes de fragments chromosomiques) avec les gènes proches. Enfin, leur potentielle fonction biologique les amène à être influencés par (et à influencer en retour) l'évolution d'autres gènes. Je montre que ne pas prendre en compte ces relations d'inter-dépendances évolutives (de coévolution) lors de l'inférence d'arbres de gènes résulte en une suresti mation des différences entre les arbres des différents gènes ainsi qu'entre les arbres des gènes et l'arbre des espèces. Des modèles permettent déjà d'intégrer la coévolution des gènes avec les espèces à la reconstruction des arbres de gènes. Par ailleurs, on connaît des modèles décrivant l'évolution des relations entre gènes, néanmoins sans intégrer ces informations à la reconstruction des arbres de gènes. Je reprends ces avancées et les combine au sein d'une méthode qui modifie les arbres de gènes selon un critère qui prend en compte les séquences ainsi que des relations de coévolution avec les espèces et d'autres gènes. Cette méthode, appliquée à des mammifères et des champignons, permet de produire des histoires de gènes cohérentes entre elle

Phylogeny of dependencies and dependencies of phylogenies in genes and genomes

L'évolution moléculaire, basée sur l'étude des données de séquençage, s'est imposée comme une approche majeure pour l'étude de l'Histoire des organismes vivants (notamment à travers les arbres phylogénétiques). Ses méthodes classiques reposent sur un découpage des génomes en entités supposées indépendantes : les gènes. Or, les gènes n'évoluent pas indépendamment : au sein de l'histoire des espèces qui le portent, l'histoire d'un gène s'inscrit. En outre, leur position le long des chromosomes fait qu'ils partagent des événements de mutations structurales (duplications, pertes de fragments chromosomiques) avec les gènes proches. Enfin, leur potentielle fonction biologique les amène à être influencés par (et à influencer en retour) l'évolution d'autres gènes. Je montre que ne pas prendre en compte ces relations d'inter-dépendances évolutives (de coévolution) lors de l'inférence d'arbres de gènes résulte en une suresti mation des différences entre les arbres des différents gènes ainsi qu'entre les arbres des gènes et l'arbre des espèces. Des modèles permettent déjà d'intégrer la coévolution des gènes avec les espèces à la reconstruction des arbres de gènes. Par ailleurs, on connaît des modèles décrivant l'évolution des relations entre gènes, néanmoins sans intégrer ces informations à la reconstruction des arbres de gènes. Je reprends ces avancées et les combine au sein d'une méthode qui modifie les arbres de gènes selon un critère qui prend en compte les séquences ainsi que des relations de coévolution avec les espèces et d'autres gènes. Cette méthode, appliquée à des mammifères et des champignons, permet de produire des histoires de gènes cohérentes entre ellesMolecular evolution, based on the study of sequencing data, established itself as a fundamental approach in the study of the history of living organisms (noticeably through the inference of phylogenetic trees). Classical molecular evolution methods rely on the decomposition of genomes into entities that are supposed independent: genes. However we know that genes do not evolve independently: their potential biological function lead them to be influenced by (and influence) the evolution of other genes. Moreover, their position along chromosomes imply that they share events of structural mutations (duplication, loss of a chromosome fragment) with neighbouring genes. Similarly, a gene individual history inscribes itself in the history of the species that bears it. I show that not taking into account this inter-dependency relationships (co- evolutionary relationships) during the inference of gene trees results in an overesti- mation of the differences between gene trees as well as between gene tree and species tree. Modelling efforts these last year have allowed the integration of gene and species co-evolution information to the reconstruction of gene trees. Besides, researchers have proposed models describing the evolution of the relationships linking genes, but without integration of this information in the tree building process. My works aim to combine these advances in a method that modify gene trees according to a criterion that integrates sequence information and information coming from co-evolution relationships. This method, applied to mammals and fungi, leads to gene histories that are more congruent (simpler adjacency histories, longer events of loss or transfer, ...

Nucleotide, gene and genome evolution : a score to bind them all

National audienceLe document est un résumé étend

Nucleotide, gene and genome evolution : a score to bind them all

National audienceLe document est un résumé étend

HyLiTE: accurate and flexible analysis of gene expression in hybrid and allopolyploid species

BACKGROUND: Forming a new species through the merger of two or more divergent parent species is increasingly seen as a key phenomenon in the evolution of many biological systems. However, little is known about how expression of parental gene copies (homeologs) responds following genome merger. High throughput RNA sequencing now makes this analysis technically feasible, but tools to determine homeolog expression are still in their infancy. RESULTS: Here we present HyLiTE – a single-step analysis to obtain tables of homeolog expression in a hybrid or allopolyploid and its parent species directly from raw mRNA sequence files. By implementing on-the-fly detection of diagnostic parental polymorphisms, HyLiTE can perform SNP calling and read classification simultaneously, thus allowing HyLiTE to be run as parallelized code. HyLiTE accommodates any number of parent species, multiple data sources (including genomic DNA reads to improve SNP detection), and implements a statistical framework optimized for genes with low to moderate expression. CONCLUSIONS: HyLiTE is a flexible and easy-to-use program designed for bench biologists to explore patterns of gene expression following genome merger. HyLiTE offers practical advantages over manual methods and existing programs, has been designed to accommodate a wide range of genome merger systems, can identify SNPs that arose following genome merger, and offers accurate performance on non-model organisms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-014-0433-8) contains supplementary material, which is available to authorized users

A Comprehensive Evolutionary Scenario of Cell Division and Associated Processes in the Firmicutes

International audienceThe cell cycle is a fundamental process that has been extensively studied in bacteria. However, many of its components and their interactions with machineries involved in other cellular processes are poorly understood. Furthermore, most knowledge relies on the study of a few models, but the real diversity of the cell division apparatus and its evolution are largely unknown. Here, we present a massive in-silico analysis of cell division and associated processes in around 1,000 genomes of the Firmicutes, a major bacterial phylum encompassing models (i.e. Bacillus subtilis, Streptococcus pneumoniae, and Staphylococcus aureus), as well as many important pathogens. We analyzed over 160 proteins by using an original approach combining phylogenetic reconciliation, phylogenetic profiles, and gene cluster survey. Our results reveal the presence of substantial differences among clades and pinpoints a number of evolutionary hotspots. In particular, the emergence of Bacilli coincides with an expansion of the gene repertoires involved in cell wall synthesis and remodeling. We also highlight major genomic rearrangements at the emergence of Streptococcaceae. We establish a functional network in Firmicutes that allows identifying new functional links inside one same process such as between FtsW (peptidoglycan polymerase) and a previously undescribed Penicilin-Binding Protein or between different processes, such as replication and cell wall synthesis. Finally, we identify new candidates involved in sporulation and cell wall synthesis. Our results provide a previously undescribed view on the diversity of the bacterial cell cycle, testable hypotheses for further experimental studies, and a methodological framework for the analysis of any other biological system