An ancient ecospecies of Helicobacter pylori found in Indigenous populations and animal adapted lineages

The colonization of our stomachs by Helicobacter pylori is believed to predate the oldest splits between extant human populations. We identify a “Hardy” ecospecies of H. pylori associated with indigenous groups, isolated from people in Siberia, Canada, USA and Chile. The ecospecies shares the ancestry of “Ubiquitous” H. pylori from the same geographical region in most of the genome but has nearly fixed SNP differences in 100 genes, many of which encode outer membrane proteins and host interaction factors. For these parts of the genome, the ecospecies has a separate, independently evolving gene pool with a distinct evolutionary history. H. acinonychis , found in big cats, and a newly identified primate-associated lineage both belong to the Hardy ecospecies and both represent human to animal host jumps. Most strains from the ecospecies encode an additional iron-dependent urease that is shared by Helicobacter from carnivorous hosts, as well as a tandem duplication of vacA , encoding the vacuolating toxin. We conclude that H. pylori split into two highly distinct ecospecies in Africa and that both dispersed around the globe with humans, but the Hardy ecospecies has gone extinct in most parts of the world. Our analysis also pushes back the likely length of the association between H. pylori and humans. ### Competing Interest Statement The authors have declared no competing interest. The list of strains used are provided in the Supplementary Tables S1 and S2. The newly sequenced strains have been deposited on Enterobase and will be made available upon publication. The public strains can be found on Enterobase, NCBI, BIGs and figshare. The scripts for most of the analysis (except for the fineSTRUCTURE and chromosome painting ones) are available on github (). In particular, these scripts contain the detail on how most of the analysis was done and the parameters chosen.