Analysis of the homB and homA sequences revealed a complete ORF in the majority of the H. pylori strains tested, truncated genes being detected Tariquidar in only 5.7% of the cases. Interestingly, in three of the four out-of-frame homB sequences, the frameshift mutations occurred in short homopolymeric tracts, suggesting that homB displays phase variation and may be regulated by slipped-strand mispairing mechanism, which was not the case for the out-of-frame homA sequences. Phase variability has been reported to be a consistent marker for genes involved in niche adaptation and

immune evasion [23, 24]. Several H. pylori genes belonging to different functional classes have been established as phase variable genes [25, 26], among which are OMP-encoding genes involved in adherence, such as sabA [6], hopZ [27], babB [28] and oipA [29]. HomB was previously found to contribute to H. pylori adherence [9]. Thus, the on/off switch of these genes would provide the bacterial population with a dynamic adherence pattern, as was SC79 molecular weight experimentally demonstrated for bab adherence genes [20, 28]. Based on the two mechanisms proposed

for regulation of homB and homA gene expression, i.e., phase variation and intra/intergenomic recombination events, it can be CA4P nmr speculated that these genes are implicated in the adaptation of H. pylori to its human host as well. However, the fact that only 5.7% of the strains have truncated homA/B sequences at loci A and B does not mean that the gene is not expressed in vivo. Indeed, the phase variation mechanism may allow the in vivo expression. Furthermore, the existence of a third locus, as was reported for babA/B [30], cannot be excluded, although previous hybridization experiments never revealed an additional locus [8, 9]. Phylogenetic reconstruction of homB and

homA genes was influenced by the geographical origin of the 17-DMAG (Alvespimycin) HCl strains, with East Asian and Western strains showing the greatest divergence. This same clustering was observed for the paralogous genes babA and babB [31]. Overall, homB and homA displayed identical molecular mean distance at both nucleotide and amino acid levels. Nucleotide substitution rates were also similar for both genes suggesting that they are both subjected to parallel functional constraints. The segmental phylogenetic analysis showed the highest level of diversity for segment 2 of both genes, the middle allele-defining region, in comparison with the more conserved segments 1 and 3. This suggests that a higher degree of variation is allowed for segment 2, supporting the hypothesis that this gene segment is involved in the generation of antigenic diversity. Another interesting point is that segment 3 of both homB and homA genes from the same strain clustered together in the phylogenetic tree, which is indicative of concerted evolution.