Abstract
Helicobacter pylori is a bacterium that lives in the human stomach and is a major risk factor for gastric cancer and ulcers. H.pylori is host dependent and has been carried with human populations around the world after their departure from Africa. We wished to investigate how H.pylori has coevolved with its host during that time, focusing on strains from Japanese and European populations, given that gastric cancer incidence is high in Japanese populations, while low in European. A positive selection analysis of eight H.pylori genomes was conducted, using maximum likelihood based pairwise comparisons in order to 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, while four European H.pylori genomes suggests 16–21 genes; few of the genes identified were in common between lineages. Of the identified genes which were annotated, 38% possessed homologs associated with pathogenicity and / or host adaptation, consistent with their involvement in a coevolutionary ‘arms race’ with the host. Given the efficacy of identifying host interaction factors de novo, in the absence of functionally annotated homologs our evolutionary approach may have value in identifying novel genes which H.pylori employs to interact with the human gut environment. In addition, the larger number of genes inferred as being under positive selection in Japanese strains compared to European implies a stronger overall adaptive pressure, potentially resulting from an elevated immune response which may be linked to increased inflammation, an initial stage in the development of gastric cancer.
Highlights
Helicobacter pylori is a Gram negative bacterium that colonizes the human stomach and is adapted to its harsh acidic conditions to such an extent that it is completely dependent on its host
While H.pylori infection is a major risk factor for gastric cancer [5], not all epidemiological studies have shown a direct relationship between H.pylori infection and gastric cancer [6]
It is notable that the incidence of gastric cancer has fallen over the past few decades in Europe [9] from a 19th century high in some countries [10, 11], and this reduction has been attributed to a variety of factors such as a drop in smoking, changes in diet and possibly a reduction in H.pylori infection [12]
Summary
Helicobacter pylori is a Gram negative bacterium that colonizes the human stomach and is adapted to its harsh acidic conditions to such an extent that it is completely dependent on its host. While H.pylori infection is a major risk factor for gastric cancer [5], not all epidemiological studies have shown a direct relationship between H.pylori infection and gastric cancer [6]. These inconsistencies may be due in part to additional factors such as smoking, alcohol consumption and diet, variations in the immune response, as well as the H.pylori genotype [7, 8]. The effects of H.pylori infection on the host appear more complex than a host–pathogen interaction
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