title: Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination.
abstract: Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori vary, particularly in their mid region (which may be type m1 or m2) and their signal peptide coding region (type s1 or s2). We investigated nucleotide diversity among vacA alleles in strains from several locales in Asia, South America, and the USA. Phylogenetic analysis of vacA mid region sequences from 18 strains validated the division into two main groups (m1 and m2) and showed further significant divisions within these groups. Informative site analysis demonstrated one example of recombination between m1 and m2 alleles, and several examples of recombination among alleles within these groups. Recombination was not sufficiently extensive to destroy phylogenetic structure entirely. Synonymous nucleotide substitution rates were markedly different between regions of vacA, suggesting different evolutionary divergence times and implying horizontal transfer of genetic elements within vacA. Non-synonymous/synonymous rate ratios were greater between m1 and m2 sequences than among m1 sequences, consistent with m1 and m2 alleles encoding functions fitting strains for slightly different ecological niches.
authors.affiliation: School of Medical and Surgical Sciences, Division of Gastroenterology, University Hospital, University of Nottingham, Nottingham NG7 2UH.
authors.forename: J C
authors.initials: JC
authors.lastname: Atherton
authors.forename: P M
authors.initials: PM
authors.lastname: Sharp
authors.forename: T L
authors.initials: TL
authors.lastname: Cover
authors.forename: G
authors.initials: G
authors.lastname: Gonzalez-Valencia
authors.forename: R M
authors.initials: RM
authors.lastname: Peek
authors.forename: S A
authors.initials: SA
authors.lastname: Thompson
authors.forename: C J
authors.initials: CJ
authors.lastname: Hawkey
authors.forename: M J
authors.initials: MJ
authors.lastname: Blaser
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D003603:Cytotoxins / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D011995:Recombination, Genetic
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D004269:DNA, Bacterial; C074689:VacA protein, Helicobacter pylori