Macroevolution of gastric Helicobacter species unveils interspecies admixture and time of divergence

Since the discovery of the human pathogen Helicobacter pylori, various other Helicobacter species have been identified in the stomach of domesticated and wild mammals. To better understand the evolutionary history of these ecologically similar but genetically distinct species, we analyzed 108 gastric Helicobacter genomes and included 54 enterohepatic Helicobacter genomes for comparison purposes. An admixture analysis supported the presence of an ecological barrier, preventing the genetic exchange between the gastric and enterohepatic Helicobacter species, and unraveled many gene flow events within and across species residing in the stomach. As pets can be colonized by multiple gastric Helicobacter species, the genetic exchange between the canine and feline strains was evident, with H. heilmannii and H. bizzozeronii showing the highest interspecies recombination. An admixture between H. pylori (in particular, the ancestral African strains), H. acinonychis from wild felines and H. cetorum from marine mammals was also identified. Because these latter species do not share the same host, this phenomenon is most likely a remaining signal of shared ancestry. A reconstruction of the time of divergence of the gastric Helicobacter spp. revealed that the domestic animal-related Helicobacter species evolved in parallel with H. pylori and its two closest relatives (H. acinonychis and H. cetorum), rather than together.