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 coevolution
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 humanbacterial
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.