Imperial College London

DrFlorentLassalle

Faculty of MedicineSchool of Public Health

Visiting Researcher
 
 
 
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Contact

 

+44 (0)20 7594 1379f.lassalle CV

 
 
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Location

 

UG13Praed StreetSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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25 results found

Horesh G, Taylor-Brown A, McGimpsey S, Lassalle F, Corander J, Heinz E, Thomson NRet al., 2021, Different evolutionary trends form the twilight zone of the bacterial pan-genome

<jats:title>Abstract</jats:title><jats:p>The pan-genome is defined as the combined set of all genes in the gene pool of a species. Pan-genome analyses have been very useful in helping to understand different evolutionary dynamics of bacterial species: an open pan-genome often indicates a free-living lifestyle with metabolic versatility, while closed pan-genomes are linked to host-restricted, ecologically specialised bacteria. A detailed understanding of the species pan-genome has also been instrumental in tracking the phylodynamics of emerging drug resistance mechanisms and drug resistant pathogens. However, current approaches to analyse a species’ pan-genome do not take the species population structure into account, nor do they account for the uneven sampling of different lineages, as is commonplace due to over-sampling of clinically relevant representatives. Here we present the application of a population structure-aware approach for classifying genes in a pan-genome based on within-species distribution. We demonstrate our approach on a collection of 7,500 <jats:italic>E. coli</jats:italic> genomes, one of the most-studied bacterial species used as a model for an open pan-genome. We reveal clearly distinct groups of genes, clustered by different underlying evolutionary dynamics, and provide a more biologically informed and accurate description of the species’ pan-genome.</jats:p>

Journal article

Lassalle F, Dastgheib SMM, Zhao F-J, Zhang J, Verbag S, Fruhling A, Brinkmann H, Osborne T, Sikorski J, Balloux F, Didelot X, Santini J, Petersen Jet al., 2021, Phylogenomics reveals the basis of adaptation of Pseudorhizobium species to extreme environments and supports a taxonomic revision of the genus, Systematic and Applied Microbiology, Vol: 44, Pages: 1-14, ISSN: 0172-5564

The family Rhizobiaceae includes many genera of soil bacteria, often isolated for their association with plants. Herein, we investigate the genomic diversity of a group of Rhizobium species and unclassified strains isolated from atypical environments, including seawater, rock matrix or polluted soil. Based on whole-genome similarity and core genome phylogeny, we show that this group corresponds to the genus Pseudorhizobium. We thus reclassify Rhizobium halotolerans, R. marinum, R. flavum and R. endolithicum as P. halotolerans sp. nov., P. marinum comb. nov. , P. flavum comb. nov. and P. endolithicum comb. nov. , respectively, and show that P. pelagicum is a synonym of P. marinum . We also delineate a new chemolithoautotroph species, P. banfieldiae sp. nov. , whose type strain is NT-26 T (= DSM 106348 T = CFBP 8663 T ) . This genome-based classification was supported by a chemotaxonomic comparison, with increasing taxonomic resolution provided by fatty acid, protein and metabolic profiles. In addition, we used a phylogenetic approach to infer scenarios of duplication, horizontal transfer and loss for all genes in the Pseudorhizobium pangenome. We thus identify the key functions associated with the diversification of each species and higher clades, shedding light on the mechanisms of adaptation to their respective ecological niches. Respiratory proteins acquired at the origin of Pseudorhizobium were combined with clade-specific genes to enable different strategies for detoxification and nutrition in harsh, nutrient- poor environments.

Journal article

Kuzmanović N, Biondi E, Overmann J, Puławska J, Verbarg S, Smalla K, Lassalle Fet al., 2020, Revisiting the taxonomy of Allorhizobium vitis (i.e. Agrobacterium vitis) using genomics - emended description of All. vitis sensu stricto and description of Allorhizobium ampelinum sp. nov

<jats:title>Abstract</jats:title><jats:p><jats:italic>Allorhizobium vitis</jats:italic> (formerly named <jats:italic>Agrobacterium vitis</jats:italic> or <jats:italic>Agrobacterium</jats:italic> biovar 3) is the primary causative agent of crown gall disease of grapevine worldwide. Whole-genome sequence comparisons and phylogenomic analysis of various <jats:italic>All. vitis</jats:italic> strains clearly indicated that <jats:italic>All. vitis</jats:italic> is not a single species, but represents a species complex composed of at least four genomic species. Thus, we amended the description of <jats:italic>All. vitis</jats:italic> which now refers to a restricted group of strains within the <jats:italic>All. vitis</jats:italic> complex (i.e. <jats:italic>All. vitis sensu stricto</jats:italic>) and proposed a description of a novel species <jats:italic>All. ampelinum</jats:italic> sp. nov. The type strain of <jats:italic>All. vitis sensu stricto</jats:italic> remains the existing type strain of <jats:italic>All. vitis</jats:italic>, K309<jats:sup>T</jats:sup> (= <jats:underline>NCPPB 3554</jats:underline><jats:sup>T</jats:sup> =HAMBI 1817<jats:sup>T</jats:sup> = <jats:underline>ATCC 49767</jats:underline><jats:sup>T</jats:sup> = CIP 105853<jats:sup>T</jats:sup> = <jats:underline>ICMP 10752</jats:underline><jats:sup>T</jats:sup> = <jats:underline>IFO 15140</jats:underline><jats:sup>T</jats:sup> = <jats:underline>JCM 21033</jats:underline><jats:sup>T</jats:sup> = <jats:underline>LMG 8750</jats:underline><jats:sup>T</jats:sup> = <jats:underline>NBRC 15140</jats:underline><jats:sup>T</jats:sup>). The type strain of <jats:ita

Journal article

Teulet A, Gully D, Rouy Z, Camuel A, Koebnik R, Giraud E, Lassalle Fet al., 2020, Phylogenetic distribution and evolutionary dynamics of nod and T3SS genes in the genus Bradyrhizobium., Microb Genom, Vol: 6

Bradyrhizobium are abundant soil bacteria and the major symbiont of legumes. The recent availability of Bradyrhizobium genome sequences provides a large source of information for analysis of symbiotic traits. In this study, we investigated the evolutionary dynamics of the nodulation genes (nod) and their relationship with the genes encoding type III secretion systems (T3SS) and their effectors among bradyrhizobia. Based on the comparative analysis of 146 Bradyrhizobium genome sequences, we identified six different types of T3SS gene clusters. The two predominant cluster types are designated RhcIa and RhcIb and both belong to the RhcI-T3SS family previously described in other rhizobia. They are found in 92/146 strains, most of them also containing nod genes. RhcIa and RhcIb gene clusters differ in the genes they carry: while the translocon-encoding gene nopX is systematically found in strains containing RhcIb, the nopE and nopH genes are specifically conserved in strains containing RhcIa, suggesting that these last two genes might functionally substitute nopX and play a role related to effector translocation. Phylogenetic analysis suggests that bradyrhizobia simultaneously gained nod and RhcI-T3SS gene clusters via horizontal transfer or subsequent vertical inheritance of a symbiotic island containing both. Sequence similarity searches for known Nop effector proteins in bradyrhizobial proteomes revealed the absence of a so-called core effectome, i.e. that no effector is conserved among all Bradyrhizobium strains. However, NopM and SUMO proteases were found to be the main effector families, being represented in the majority of the genus. This study indicates that bradyrhizobial T3SSs might play a more significant symbiotic role than previously thought and provides new candidates among T3SS structural proteins and effectors for future functional investigations.

Journal article

Lassalle F, Didelot X, 2020, Bacterial microevolution and the pangenome, The Pangenome: Diversity, Dynamics and Evolution of Genomes, Pages: 129-149, ISBN: 9783030382803

The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history.

Book chapter

Holt K, Lassalle F, Wyres K, Wick R, Mostowy Ret al., 2020, Diversity and evolution of surface polysaccharide synthesis loci in Enterobacteriales, The ISME Journal: multidisciplinary journal of microbial ecology, Vol: 14, Pages: 1713-1730, ISSN: 1751-7362

Bacterial capsules and lipopolysaccharides are diverse surface polysaccharides (SPs) that serve as the frontline for interactions with the outside world. While SPs can evolve rapidly, their diversity and evolutionary dynamics across different taxonomic scales has not been investigated in detail. Here, we focused on the bacterial order Enterobacteriales (including the medically relevant Enterobacteriaceae), to carry out comparative genomics of two SP locus synthesis regions, cps and kps, using 27,334 genomes from 45 genera. We identified high-quality cps loci in 22 genera and kps in 11 genera, around 4% of which were detected in multiple species. We found SP loci to be highly dynamic genetic entities: their evolution was driven by high rates of horizontal gene transfer (HGT), both of whole loci and component genes, and relaxed purifying selection, yielding large repertoires of SP diversity. In spite of that, we found the presence of (near-)identical locus structures in distant taxonomic backgrounds that could not be explained by recent exchange, pointing to long-term selective preservation of locus structures in some populations. Our results reveal differences in evolutionary dynamics driving SP diversity within different bacterial species, with lineages of Escherichia coli, Enterobacter hormaechei and Klebsiella aerogenes most likely to share SP loci via recent exchange; and lineages of Salmonella enterica, Citrobacter sakazakii and Serratia marcescens most likely to share SP loci via other mechanisms such as long-term preservation. Overall, the evolution of SP loci in Enterobacteriales is driven by a range of evolutionary forces and their dynamics and relative importance varies between different species.

Journal article

Lassalle F, Beale MA, Bharucha T, Williams CA, Williams RJ, Cudini J, Goldstein R, Haque T, Depledge DP, Breuer Jet al., 2020, Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses, Virus Evolution, Vol: 6, Pages: 1-14, ISSN: 2057-1577

Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70 per cent of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. In contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.

Journal article

Lassalle F, Beale MA, Bharucha T, Williams CA, Williams RJ, Cudini J, Goldstein R, Haque T, Depledge DP, Breuer Jet al., 2019, Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70% of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. By contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.</jats:p>

Working paper

Lassalle F, Dastgheib SMM, Zhao F-J, Zhang J, Verbarg S, Frühling A, Brinkmann H, Osborne TH, Sikorski J, Balloux F, Didelot X, Santini JM, Petersen Jet al., 2019, Phylogenomic analysis reveals the basis of adaptation of Pseudorhizobium species to extreme environments

<jats:title>Abstract</jats:title><jats:p>The family <jats:italic>Rhizobiaceae</jats:italic> includes many genera of soil bacteria, often isolated for their association with plants. Herein, we investigate the genomic diversity of a group of <jats:italic>Rhizobium</jats:italic> species and unclassified strains isolated from atypical environments, including seawater, rock matrix or polluted soil. Based on whole-genome similarity and core genome phylogeny, we show that this group corresponds to the genus <jats:italic>Pseudorhizobium.</jats:italic> We thus reclassify <jats:italic>Rhizobium halotolerans, R. marinum, R. flavum</jats:italic> and <jats:italic>R. endolithicum</jats:italic> as <jats:italic>P. halotolerans</jats:italic> comb. nov., <jats:italic>P. marinum</jats:italic> comb. nov.<jats:italic>, P. flavum</jats:italic> comb. nov. and <jats:italic>R. endolithicum</jats:italic> comb. nov., respectively, and show that <jats:italic>P. pelagicum</jats:italic> is a synonym of <jats:italic>P. marinum</jats:italic>. We also delineate a new chemolithoautotroph species, <jats:italic>P. banfieldiae</jats:italic> sp. nov., whose type strain is NT-26<jats:sup>T</jats:sup> (= DSM 106348<jats:sup>T</jats:sup> = CFBP 8663<jats:sup>T</jats:sup>). This genome-based classification was supported by a chemotaxonomic comparison, with gradual taxonomic resolution provided by fatty acid, protein and metabolic profiles. In addition, we used a phylogenetic approach to infer scenarios of duplication, horizontal transfer and loss for all genes in the <jats:italic>Pseudorhizobium</jats:italic> pangenome. We thus identify the key functions associated with the diversification of each species and higher clades, shedding light on the mechanisms of adaptation to their respective ecological

Journal article

Lassalle F, Veber P, Jauneikaite E, Didelot Xet al., 2019, Automated reconstruction of all gene histories in large bacterial pangenome datasets and search for co-evolved gene modules with Pantagruel

<jats:title>Abstract</jats:title><jats:p>The availability of bacterial pangenome data grows exponentially, requiring efficient new methods of analysis. Currently popular approaches for the fast comparison of genomes have the drawback of not being based on explicit evolutionary models of diversification. Making sense of bacterial genome evolution, and notably in the accessory genome, requires however to take into account the complex processes by which the genomes evolve. Here we present the <jats:italic>Pantagruel</jats:italic> bioinformatic software pipeline, which enables the construction of a complete bacterial pangenome database geared towards the inference of gene evolution scenarios using gene tree/species tree reconciliation. <jats:italic>Pantagruel</jats:italic> is a modular pipeline that combines state-of-the-art external software with unique new methods. It can be executed with no supervision to perform a standard pangenome analysis, or be configured by advanced users to integrate methods of choice. A relational database underlies its data structure, allowing efficient retrieval of the large-scale data generated by integrative analyses of pangenome evolutionary history. From the reconstructed gene evolution scenarios, two main outputs are derived: firstly the gene tree-aware assignation of orthology, allowing the fine analysis of gene gain and loss history over the species phylogeny, and secondly a network of gene-to-gene association based on correlated events in scenarios of gene evolution, leading to the definition of co-evolved gene modules. <jats:italic>Pantagruel</jats:italic> is available as an open source software package at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://github.com/flass/pantagruel">https://github.com/flass/pantagruel</jats:ext-link>.</jats:p>

Journal article

Wegner F, Lassalle F, Depledge DP, Balloux F, Breuer Jet al., 2019, Co-evolution of sites under immune selection shapes Epstein-Barr Virus population structure, Molecular Biology and Evolution, Vol: 36, Pages: 2512-2521, ISSN: 0737-4038

Epstein-Barr virus (EBV) is one of the most common viral infections in humans and persists within its host for life. EBV therefore represents an extremely successful virus that has evolved complex strategies to evade the host’s innate and adaptive immune response during both initial and persistent stages of infection. Here, we conducted a comparative genomics analysis on 223 whole genome sequences of world-wide EBV strains. We recover extensive genome-wide linkage disequilibrium (LD) despite pervasive genetic recombination. This pattern is explained by the global EBV population being subdivided into three main sub-populations, one primarily found in East Asia, one in Southeast Asia and Oceania, and the third including most of the other globally distributed genomes we analyzed. Additionally, sites in LD were overrepresented in immunogenic genes. Taken together, our results suggest that host immune selection and local adaptation to different human host populations has shaped the genome-wide patterns of genetic diversity in EBV.

Journal article

Holt KE, Lassalle F, Wyres KL, Wick R, Mostowy RJet al., 2019, Diversity and evolution of surface polysaccharide synthesis loci in Enterobacteriales, Publisher: Cold Spring Harbor Laboratory

<jats:p>Bacterial capsules and lipopolysaccharides are diverse surface polysaccharides (SPs) that serve as the frontline for interactions with the outside world. While SPs can evolve rapidly, their diversity and evolutionary dynamics across different taxonomic scales has not been investigated in detail. Here, we focused on the bacterial order Enterobacteriales (including the medically-relevant Enterobacteriaceae), to carry out comparative genomics of two SP locus synthesis regions,<jats:italic>cps</jats:italic>and<jats:italic>kps</jats:italic>, using 27,334 genomes from 45 genera. We identified high-quality<jats:italic>cps</jats:italic>loci in 22 genera and<jats:italic>kps</jats:italic>in 11 genera, around 4% of which were detected in multiple species. We found SP loci to be highly dynamic genetic entities: their evolution was driven by high rates of horizontal gene transfer (HGT), both of whole loci and component genes, and relaxed purifying selection, yielding large repertoires of SP diversity. In spite of that, we found the presence of (near-)identical locus structures in distant taxonomic backgrounds that could not be explained by recent exchange, pointing to long-term selective preservation of locus structures in some populations. Our results reveal differences in evolutionary dynamics driving SP diversity within different bacterial species, with lineages of<jats:italic>Escherichia coli</jats:italic>,<jats:italic>Enterobacter hormachei</jats:italic>and<jats:italic>Klebsiella aerogenes</jats:italic>most likely to share SP loci via recent exchange; and lineages of<jats:italic>Salmonella enterica</jats:italic>,<jats:italic>Citrobacter sakazakii</jats:italic>and<jats:italic>Serratia marcescens</jats:italic>most likely to share SP loci via other mechanisms such as long-term preservation. Overall, the evolution of SP loci in Enterobacteriales

Working paper

Mafakheri H, Taghavi SM, Puławska J, de Lajudie P, Lassalle F, Osdaghi Eet al., 2019, Two Novel Genomospecies in the Agrobacterium tumefaciens Species Complex Associated with Rose Crown Gall, Phytopathology, ISSN: 0031-949X

Journal article

de Lajudie PM, Andrews M, Ardley J, Eardly B, Jumas-Bilak E, Kuzmanovic N, Lassalle R, Lindstrom K, Mhamdi R, Martinez-Romero E, Moulin L, Mousavi SA, Nesme X, Peix A, Pulawska J, Steenkamp E, Stepkowski T, Tian C-F, Vinuesa P, Wei G, Willems A, Zili J, Young Pet al., 2019, Minimal standards for the description of new genera and species of rhizobia and agrobacteria, INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Vol: 69, Pages: 1852-1863, ISSN: 1466-5026

Journal article

Lassalle F, Spagnoletti M, Fumagalli M, Shaw L, Dyble M, Walker C, Thomas MG, Bamberg Migliano A, Balloux Fet al., 2017, Oral microbiomes from hunter-gatherers and traditional farmers reveal shifts in commensal balance and pathogen load linked to diet., Molecular Ecology, Vol: 27, Pages: 182-195, ISSN: 0962-1083

Maladaptation to modern diets has been implicated in several chronic disorders. Given the higher prevalence of disease such as dental caries and chronic gum diseases in industrialized societies, we sought to investigate the impact of different subsistence strategies on oral health and physiology, as documented by the oral microbiome. To control for confounding variables such as environment and host genetics, we sampled saliva from three pairs of populations of hunter-gatherers and traditional farmers living in close proximity in the Philippines. Deep shotgun sequencing of salivary DNA generated high-coverage microbiomes along with human genomes. Comparing these microbiomes with publicly available data from individuals living on a Western diet revealed that abundance ratios of core species were significantly correlated with subsistence strategy, with hunter-gatherers and Westerners occupying either end of a gradient of Neisseria against Haemophilus, and traditional farmers falling in between. Species found preferentially in hunter-gatherers included microbes often considered as oral pathogens, despite their hosts' apparent good oral health. Discriminant analysis of gene functions revealed vitamin B5 autotrophy and urease-mediated pH regulation as candidate adaptations of the microbiome to the hunter-gatherer and Western diets, respectively. These results suggest that major transitions in diet selected for different communities of commensals and likely played a role in the emergence of modern oral pathogens.

Journal article

Lassalle F, Planel R, Penel S, Chapulliot D, Barbe V, Dubost A, Calteau A, Vallenet D, Mornico D, Bigot T, Guéguen L, Vial L, Muller D, Daubin V, Nesme Xet al., 2017, Ancestral genome estimation reveals the history of ecological diversification in Agrobacterium, Genome Biology and Evolution, Vol: 9, Pages: 3413-3431, ISSN: 1759-6653

Horizontal gene transfer (HGT) is considered as a major source of innovation in bacteria, and as such is expected to drive adaptation to new ecological niches. However, among the many genes acquired through HGT along the diversification history of genomes, only a fraction may have actively contributed to sustained ecological adaptation. We used a phylogenetic approach accounting for the transfer of genes (or groups of genes) to estimate the history of genomes in Agrobacterium biovar 1, a diverse group of soil and plant-dwelling bacterial species. We identified clade-specific blocks of cotransferred genes encoding coherent biochemical pathways that may have contributed to the evolutionary success of key Agrobacterium clades. This pattern of gene coevolution rejects a neutral model of transfer, in which neighboring genes would be transferred independently of their function and rather suggests purifying selection on collectively coded acquired pathways. The acquisition of these synapomorphic blocks of cofunctioning genes probably drove the ecological diversification of Agrobacterium and defined features of ancestral ecological niches, which consistently hint at a strong selective role of host plant rhizospheres.

Journal article

Lassalle F, Depledge DP, Reeves MB, Brown AC, Christiansen MT, Tutill HJ, Williams RJ, Einer-Jensen K, Holdstock J, Atkinson C, Brown JR, van Loenen FB, Clark DA, Griffiths PD, Verjans GMGM, Schutten M, Milne RSB, Balloux F, Breuer Jet al., 2016, Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes, Virus Evolution, Vol: 2, ISSN: 2057-1577

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomati

Journal article

Lassalle F, Muller D, Nesme X, 2015, Ecological speciation in bacteria: reverse ecology approaches reveal the adaptive part of bacterial cladogenesis, RESEARCH IN MICROBIOLOGY, Vol: 166, Pages: 729-741, ISSN: 0923-2508

Journal article

Ravenhall M, Skunca N, Lassalle F, Dessimoz Cet al., 2015, Inferring Horizontal Gene Transfer, PLoS Computational Biology, Vol: 11, ISSN: 1553-734X

Horizontal or Lateral Gene Transfer (HGT or LGT) is the transmission of portions of genomicDNA between organisms through a process decoupled from vertical inheritance. In the presenceof HGT events, different fragments of the genome are the result of different evolutionaryhistories. This can therefore complicate the investigations of evolutionary relatedness of lineagesand species. Also, as HGT can bring into genomes radically different genotypes fromdistant lineages, or even new genes bearing new functions, it is a major source of phenotypicinnovation and a mechanism of niche adaptation. For example, of particular relevance tohuman health is the lateral transfer of antibiotic resistance and pathogenicity determinants,leading to the emergence of pathogenic lineages [1]. Computational identification of HGTevents relies upon the investigation of sequence composition or evolutionary history ofgenes. Sequence composition-based ("parametric") methods search for deviations from thegenomic average, whereas evolutionary history-based ("phylogenetic") approaches identifygenes whose evolutionary history significantly differs from that of the host species. The evaluationand benchmarking of HGT inference methods typically rely upon simulated genomes,for which the true history is known. On real data, different methods tend to infer different HGTevents, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events

Journal article

Vieira FG, Lassalle F, Korneliussen TS, Fumagalli Met al., 2015, Improving the estimation of genetic distances from Next-Generation Sequencing data, Biological Journal of the Linnean Society, Vol: 117, Pages: 139-149, ISSN: 0024-4066

Next-Generation Sequencing (NGS) technologies have revolutionized research in evolutionary biology, by increasing the sequencing speed and reducing the experimental costs. However, sequencing errors are higher than in traditional technologies and, furthermore, many studies rely on low-depth sequencing. Under these circumstances, the use of standard methods for inferring genotypes leads to biased estimates of nucleotide variation, which can bias all downstream analyses. Through simulations, we assessed the bias in estimating genetic distances under several different scenarios. The results indicate that naive methods for assigning individual genotypes greatly overestimate genetic distances. We propose a novel method to estimate genetic distances that is suitable for low-depth NGS data and takes genotype call statistical uncertainty into account. We applied this method to investigate the genetic structure of domesticated and wild strains of rice. We implemented this approach in an open-source software and discuss further directions of phylogenetic analyses within this novel probabilistic framework.

Journal article

Lassalle F, Perian S, Bataillon T, Nesme X, Duret L, Daubin Vet al., 2015, GC-Content Evolution in Bacterial Genomes: The Biased Gene Conversion Hypothesis Expands, PLOS GENETICS, Vol: 11, ISSN: 1553-7404

Journal article

Ramirez-Bahena MH, Vial L, Lassalle F, Diel B, Chapulliot D, Daubin V, Nesme X, Muller Det al., 2014, Single acquisition of protelomerase gave rise to speciation of a large and diverse clade within the Agrobacterium/Rhizobium supercluster characterized by the presence of a linear chromid, MOLECULAR PHYLOGENETICS AND EVOLUTION, Vol: 73, Pages: 202-207, ISSN: 1055-7903

Journal article

Bigot T, Daubin V, Lassalle F, Perriere Get al., 2013, TPMS: a set of utilities for querying collections of gene trees, BMC Bioinformatics, Vol: 14, ISSN: 1471-2105

Background: The information in large collections of phylogenetic trees is useful for many comparative genomicstudies. Therefore, there is a need for flexible tools that allow exploration of such collections in order to retrieverelevant data as quickly as possible.Results: In this paper, we present TPMS (Tree Pattern-Matching Suite), a set of programs for handling and retrievinggene trees according to different criteria. The programs from the suite include utilities for tree collection building,specific tree-pattern search strategies and tree rooting. Use of TPMS is illustrated through three examples: systematicsearch for incongruencies in a large tree collection, a short study on the Coelomata/Ecdysozoa controversy and anevaluation of the level of support for a recently published Mammal phylogeny.Conclusion: TPMS is a powerful suite allowing to quickly retrieve sets of trees matching complex patterns in largecollection or to root trees using more rigorous approaches than the classical midpoint method. As it is made of a setof command-line programs, it can be easily integrated in any sequence analysis pipeline for an automated use.

Journal article

Andres J, Arsene-Ploetze F, Barbe V, Brochier-Armanet C, Cleiss-Arnold J, Coppee J-Y, Dillies M-A, Geist L, Joublin A, Koechler S, Lassalle F, Marchal M, Medigue C, Muller D, Nesme X, Plewniak F, Proux C, Ramirez-Bahena MH, Schenowitz C, Sismeiro O, Vallenet D, Santini JM, Bertin PNet al., 2013, Life in an Arsenic-Containing Gold Mine: Genome and Physiology of the Autotrophic Arsenite-Oxidizing Bacterium Rhizobium sp NT-26, GENOME BIOLOGY AND EVOLUTION, Vol: 5, Pages: 934-953, ISSN: 1759-6653

Journal article

Lassalle F, Campillo T, Vial L, Baude J, Costechareyre D, Chapulliot D, Shams M, Abrouk D, Lavire C, Oger-Desfeux C, Hommais F, Gueguen L, Daubin V, Muller D, Nesme Xet al., 2011, Genomic Species Are Ecological Species as Revealed by Comparative Genomics in Agrobacterium tumefaciens, Genome Biology and Evolution, Vol: 3, Pages: 762-781, ISSN: 1759-6653

The definition of bacterial species is based on genomic similarities, giving rise to the operational concept of genomic species, but the reasons of the occurrence of differentiated genomic species remain largely unknown. We used the Agrobacterium tumefaciens species complex and particularly the genomic species presently called genomovar G8, which includes the sequenced strain C58, to test the hypothesis of genomic species having specific ecological adaptations possibly involved in the speciation process. We analyzed the gene repertoire specific to G8 to identify potential adaptive genes. By hybridizing 25 strains of A. tumefaciens on DNA microarrays spanning the C58 genome, we highlighted the presence and absence of genes homologous to C58 in the taxon. We found 196 genes specific to genomovar G8 that were mostly clustered into seven genomic islands on the C58 genome—one on the circular chromosome and six on the linear chromosome—suggesting higher plasticity and a major adaptive role of the latter. Clusters encoded putative functional units, four of which had been verified experimentally. The combination of G8-specific functions defines a hypothetical species primary niche for G8 related to commensal interaction with a host plant. This supports that the G8 ancestor was able to exploit a new ecological niche, maybe initiating ecological isolation and thus speciation. Searching genomic data for synapomorphic traits is a powerful way to describe bacterial species. This procedure allowed us to find such phenotypic traits specific to genomovar G8 and thus propose a Latin binomial, Agrobacterium fabrum, for this bona fide genomic species.

Journal article

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