An African origin for the intimate association between humans and Helicobacter pylori

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Abstract
More than half of all humans are infected by the gut bacterium Helicobacter pylori, which can cause peptic ulcers and is a risk factor for stomach cancer. A major study of genetic variation in H. pylori isolates shows that the key patterns in the distribution of its genetic diversity mirror those of its human host. As in humans, there is a continuous loss of genetic diversity with increasing distance from East Africa, suggesting that humans were already infected with the ulcer-causing bacterium around 58,000 years ago when they migrated out of Africa. Humans and H. pylori also seem to have spread from East Africa over the same time scale, suggesting that their association predates the 'out of Africa' event. The team also found that the genetic make-up of H. pylori is more diverse than that of humans, so analyses of the microorganism's DNA might aid future work. As is the case with humans, Helicobacter pylori shows genetic evidence of an origin in Africa and subsequent migrations to the rest of the world. Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, although H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation1,2,3,4, the age of an association between these bacteria with humans remains highly controversial5,6. Here we show, using sequences from a large data set of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from east Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from east Africa around 58,000 yr ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues7. Taken together, our results establish that anatomically modern humans were already infected by H. pylori before their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since.