title: Small variable segments constitute a major type of diversity of bacterial genomes at the species level.
abstract: BACKGROUND
  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.
authors.affiliation: INRA, UMR1319, Micalis, Bat 222, Jouy en Josas, 78350, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Touzain
authors.forename: Erick
authors.initials: E
authors.lastname: Denamur
authors.forename: Claudine
authors.initials: C
authors.lastname: Médigue
authors.forename: Valérie
authors.initials: V
authors.lastname: Barbe
authors.forename: Meriem
authors.initials: M
authors.lastname: El Karoui
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Petit
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004269:DNA, Bacterial / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000235:genetics; D013297:Streptococcus pyogenes / Q000235:genetics
chemical_list: D004269:DNA, Bacterial