Small variable segments constitute a major type of diversity of bacterial genomes at the species level.

International audienceBACKGROUND: Analysis of large scale diversity in bacterial genomes has mainly focused on elements such as pathogenicity islands, or more generally, genomic islands. These comprise numerous genes and confer important phenotypes, which are present or absent depending on strains. We report that despite this widely accepted notion, most diversity at the species level is composed of much smaller DNA segments, 20 to 500 bp in size, which we call microdiversity. RESULTS: 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. CONCLUSIONS: 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

Organised Genome Dynamics in the Escherichia coli Species Results in Highly Diverse Adaptive Paths

The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the ∼18,000 families of orthologous genes, we found ∼2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome

European 1 : a globally important clonal complex of Mycobacterium bovis

We have identified a globally important clonal complex of Mycobacterium bovis by deletion analysis of over one thousand strains from over 30 countries. We initially show that over 99% of the strains of M. bovis, the cause of bovine tuberculosis, isolated from cattle in the Republic of Ireland and the UK are closely related and are members of a single clonal complex marked by the deletion of chromosomal region RDEu1 and we named this clonal complex European 1 (Eu1). Eu1 strains were present at less than 14% of French, Portuguese and Spanish isolates of M. bovis but are rare in other mainland European countries and Iran. However, strains of the Eu1 clonal complex were found at high frequency in former trading partners of the UK (USA, South Africa, New Zealand, Australia and Canada). The Americas, with the exception of Brazil, are dominated by the Eu1 clonal complex which was at high frequency in Argentina, Chile, Ecuador and Mexico as well as North America. Eu1 was rare or absent in the African countries surveyed except South Africa. A small sample of strains from Taiwan were non-Eu1 but, surprisingly, isolates from Korea and Kazakhstan were members of the Eu1 clonal complex. The simplest explanation for much of the current distribution of the Eu1 clonal complex is that it was spread in infected cattle, such as Herefords, from the UK to former trading partners, although there is evidence of secondary dispersion since. This is the first identification of a globally dispersed clonal complex M. bovis and indicates that much of the current global distribution of this important veterinary pathogen has resulted from relatively recent International trade in cattle.This work was funded by: TBadapt project (LSHp-CT-2007-037919); B.M. received financial support from the Swiss National Science Foundation; Swedish Research Council, Swedish Heart-Lung foundation, Swedish International Development Agency; Department of Agriculture and Rural Development Northern Ireland (project DARD0407); EU project TB-STEP (KBBE-2007-1-3-04, no. 212414); Swiss National Science Foundation (Grant No. 107559); Damien Foundation, Belgium; Commission Universitaire pour le Développement (CUD), University of Liege (Project PIC); The Wellcome Trust Livestock for Life and Animal Health in the Developing World initiatives (075833/A/04/Z); Chilean National Livestock Service -FONDOSAGC5-100-10-23 and CONICYT-FIC-R-EQU18 and by the Department of Environment, Food and Rural Affairs, UK (project SB4020).http://www.elsevier.com/locate/meegidab2012ab2013 (Author correction

Le typage moléculaire des isolats de Mycobacterium bovis

National audienceDepuis une dizaine d’années, plusieurs techniques de typage des isolats de Mycobacterium bovis ont été mises au point. Elles permettent d’affiner l’étude au-delà du niveau de l’espèce ou de la sous-espèce. 1349 isolats de M. bovis reçus ou obtenus au Laboratoire central de recherches vétérinaires de l’Afssa d’Alfort entre 1979 et août 2000 ont été analysés par spoligotypage. Dans la grande majorité des cas, les isolats typés proviennent de bovins. La combinaison de deux ou plusieurs techniques de typage pourrait être utile afin de découvrir l’origine d’un foyer ou mettre en évidence une transmission à des animaux domestiques à partir de réservoirs sauvages

Epidemiology molecular of Mycobacterium bovis in France

Haddad Nadia, Ostyn Annick, Karoui Claudine, Thorel M. F., Durand Benoît. Épidémiologie moléculaire de Mycobacterium bovis en France. In: Bulletin de l'Académie Vétérinaire de France tome 155 n°1-2, 2002. pp. 119-130

Le typage moléculaire des isolats de Mycobacterium bovis

National audienceDepuis une dizaine d’années, plusieurs techniques de typage des isolats de Mycobacterium bovis ont été mises au point. Elles permettent d’affiner l’étude au-delà du niveau de l’espèce ou de la sous-espèce. 1349 isolats de M. bovis reçus ou obtenus au Laboratoire central de recherches vétérinaires de l’Afssa d’Alfort entre 1979 et août 2000 ont été analysés par spoligotypage. Dans la grande majorité des cas, les isolats typés proviennent de bovins. La combinaison de deux ou plusieurs techniques de typage pourrait être utile afin de découvrir l’origine d’un foyer ou mettre en évidence une transmission à des animaux domestiques à partir de réservoirs sauvages

Molecular identification of <em>Mycobacterium bovis</em> strains of responsible of bovine tuberculosis outbreaks in France, in livestock and in wildlife

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Discriminatory power of spoligotyping and MLVA in French <em>M. bovis</em> strains

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