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Thus, a heightened immune response in the Japanese population may lead to both increased adaptation in H.pylori strains and increased oncogenesis. The strains examined in this analysis were isolated from individuals with a variety of different pathologies, but the signatures of positive selection that we detected are likely to have been accumulated over a longer time period than the lifespan of a single individual. More genome sequences will be required in order to fully test the [http://www.selleckchem.com/products/ldn193189.html LDN193189] hypothesis that elevated adaptation is related to increased inflammation, and the genes that are responsible for increased inflammation need to be established. A number of potential candidates have been identified in this analysis and experimental verification could be conducted on these. Relationship between transmission mode of Helicobacter pylori and pathogenicity Helicobacter pylori is often regarded as vertically inherited, but increasing evidence shows that horizontal transmission may be more common than previously recognized, especially in developing countries [83�C85]. The argument can be made that if H.pylori is entirely vertically transmitted, the observation of signatures of positive selection we detected in known and potential pathogenic [http://www.selleckchem.com/products/a-1210477.html see more] factors of H.pylori is contradictory. This is because if the bacteria are vertically transmitted they are expected to evolve to minimize harmful effects [86], while if they are horizontally transmitted then they are expected to have a degree of pathogenicity [87]. Thus, our results are inconsistent with a strictly vertical mode of transmission. The age of transmission may be important; vertical transmission has been observed from mother to child, i.e. during reproductive age. This might help to explain the late onset of [http://en.wikipedia.org/wiki/Diglyceride diglyceride] gastric cancer; it occurs after transmission has occurred and is consistent with the increasing evidence that H.pylori is beneficial, with pathogenic effects exerting themselves later in life [19]. Conclusion While there are similarities in the levels of purifying selection, Japanese H.pylori genomes have a greater number of genes inferred as being under positive selection than European strains and present new potential protein factors that interact with the host. These results help to further our understanding of the host interaction and pathogenesis of H.pylori. In particular, we propose that elevated levels of adaptation in these genomes may indicate an elevated immune response, and hypothesise that this provides a connection with elevated levels of gastric cancer in Japanese populations. In addition, in the absence of functionally annotated homologs, our procedure may have value in identifying potential novel pathogenic factors from pathogen genomes which could be crucial for adaptation to the host. SUPPLEMENTARY DATA Supplementary data is available at EMPH online.