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When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with  Helicobacter pylori , and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by  H. pylori  prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of  H. pylori  in Africa, where both humans and  H. pylori  originated. Three distinct  H. pylori  populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all  H. pylori  plus its closest relative  H. acinonychis  dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San.  H. acinonychis , which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that  H. pylori  is approximately as old as are anatomically modern humans. They also suggest that  H. pylori  may have been acquired  via  a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya.

Age of the Association between Helicobacter pylori and Man