Concerted evolution between duplicated genetic elements in Helicobacter pylori

The Helicobacter pylori genome includes a family of outer membrane proteins (OMPs) with substantial N and C-terminal identity. To better understand their evolution, the nucleotide sequences for two members, babA and babB, were determined from a worldwide group of 23 strains. The geographic origin of each strain was found to be the major determinant of phylogenetic structure, with strains of Eastern and Western origin showing greatest divergence. For strains 96-10 (Japan) and 96-74 (USA), the 5′ regions of babB are replaced with babA sequences, demonstrating that recombination occurs between the two loci. babA and babB have nearly equivalent variation in nucleotide and amino acid identity, and frequencies of synonymous and non-synonymous substitutions. Both genes have segmental conservation but within the 3′ segment, substitution patterns are nearly identical. Although babA and babB 5′ and midregion segment phylogenies show strong interstrain similarity, the 3′ segments show strong intrastrain similarity, indicative of concerted evolution. Within these 3′ segments, the lower intrastrain than interstrain frequencies of nucleotide substitutions, which are below mean background H. pylori substitution frequencies, indicate selection against intrastrain diversification. Since babA/babB gene conversions likely underlie the concerted evolution of the 3′ segments, in an experimental system, we demonstrate that gene conversions can frequently (10−3) occur in H. pylori. That these events are recA-dependent and DNase-resistant indicates their likely cause is intragenomic recombination.