Evolution of functional polymorphism in the gene coding for the Helicobacter pylori cytotoxin.

There are two functionally different alleles of the Helicobacter pylori vacA gene, which code for proteins with different in target cell specificity. The alleles (m1 and m2) differ by approximately 50% in amino acid sequence in a 300 amino acid region, the m-region, which determines specificity. An analysis of partial likelihood anomalies in a set of eight Chinese and six Western vacA genes revealed highly significant phylogenetic deviation of a region of the gene including the m-region. Phylogenetic analysis of the conserved regions of these genes failed to reveal any distinction between m1 alleles and m2 alleles, however clear cut geographic variation was observed. In the m-region, the m1 alleles also show separate clustering of Chinese and Western isolates, however the m-region of the m2 alleles has a phylogenetic structure markedly different from the rest of the gene. The data indicate that the m2 m-region was acquired and spread through the population by horizontal transfer of DNA.