Genome evolution, global diversification and spread of H. pylori (sub-) populations. Horizontal gene transfer and genome plasticity likely contributed to the evolution of pathogenic variants from non-pathogenic colonizers. Modern H. pylori populations thus derived their gene pools from ancestral populations that arose on different continents and can be correlated with different migrations of human populations and other Neolithic events such as arrival of agriculture. The beginning of agriculture and the domestication of farm animals (which seem to have occurred hand in hand but across multiple domestication events in a continent specific manner) suggest a scenario, as depicted here, which can be linked to the acquisition of virulence by H. pylori. It can be hypothesized that early bacterial communities originating from crop plants, animals or rodent pests etc. rampant in the vicinity of early human societies may have served as donors of some of the virulence gene cassettes. Such genetic elements may have been acquired by H. pylori either bit by bit or en-bloc, at some point of time, through horizontal gene transfer events. There are indirect evidences to this effect in the form of sequence and structural similarities of some of the H. pylori's virulence genes to their homologues in plant pathogens and environmental bacteria. Also, we believe that the extraneous virulence genes may have conferred some survival advantage upon H. pylori making them fitter in different human and animal hosts and, as a result, the pathogen may have spread selectively in a geographically compartmentalized manner.