Elevated levels of adaption in Helicobacter pylori genomes from Japan; a link to higher incidences of gastric cancer?

Abstract

Helicobacter pylori is a bacterium that lives in the human stomach and is a major risk factor for gastriccancer and ulcers. H.pylori is host dependent and has been carried with human populations around theworld after their departure from Africa. We wished to investigate how H.pylori has coevolved with itshost during that time, focusing on strains from Japanese and European populations, given that gastriccancer incidence is high in Japanese populations, while low in European. A positive selection analysis ofeight H.pylori genomes was conducted, using maximum likelihood based pairwise comparisons in orderto maximize the number of strain-specific genes included in the study. Using the genic Ka/Ks ratio,comparisons of four Japanese H.pylori genomes suggests 25-34 genes under positive selection, whilefour European H.pylori genomes suggests 16-21 genes; few of the genes identified were in commonbetween lineages. Of the identified genes which were annotated, 38% possessed homologs associatedwith pathogenicity and / or host adaptation, consistent with their involvement in a coevolutionary 'armsrace' with the host. Given the efficacy of identifying host interaction factors de novo, in the absence offunctionally annotated homologs our evolutionary approach may have value in identifying novel geneswhich H.pylori employs to interact with the human gut environment. In addition, the larger number ofgenes inferred as being under positive selection in Japanese strains compared to European implies astronger overall adaptive pressure, potentially resulting from an elevated immune response which maybe linked to increased inflammation, an initial stage in the development of gastric cancer.