Homologous recombination in Helicobacter pylori has been extensively described to
occur via Outer Membrane Proteins (OMPs), regulating protein expression and
generating allelic diversity, while the importance of single nucleotide polymorphisms
(SNP) remains little studied.
We used an OMP-encoding gene, homC, as a model to evaluate the weight of
positive selection in the evolution of H. pylori, by using G200 sequences obtained
from strains collected worldwide. N-site and branch-site phylogenetic analysis by
maximum likelihood models were used to identify specific codons that may be
important in homC evolution, and to evaluate the impact of selective pressure on
the geographic segregation of strains, respectively.
The N-site overall analysis showed that 14 of the 742 (1.9%) homC codons are
likely under positive selection (likelihood-ratio test (LRT), p < 10-61). Four of
these codons are located in the most variable allelic gene middle region, probably
reflecting recombination-derived hitchhiking events. On the other hand, eight
codons are located in the more conserved 5¢and 3¢ gene regions, although the
significance of this distribution remains to be clarified.
Branch-site analysis revealed 36 codons (4.9%) under positive selection (LRT,
p < 10-41), showing a non-random distribution, and 89% of these particular
codons (p < 10-3) support the phylogenetic segregation of European strains from
both African and East Asian strains. The lack of visible recombination within this
segment suggests an important biological role of point mutations in the evolution
of H. pylori OMPs.
In conclusion, homC SNP analysis suggests that, besides recombination, positive
selection contributes as well to the evolution of H. pylori OMPs
