Local adaptation of <i>Mycobacterium tuberculosis</i> on the Tibetan Plateau.

Abstract

During its global dispersal, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) has encountered varied geographic environments and host populations. Although local adaptation seems to be a plausible model for describing long-term host-pathogen interactions, genetic evidence for this model is lacking. Here, we analyzed 576 whole-genome sequences of <i>Mtb</i> strains sampled from different regions of high-altitude Tibet. Our results show that, after sequential introduction of a few ancestral strains, the Tibetan <i>Mtb</i> population diversified locally while maintaining strict separation from the <i>Mtb</i> populations on the lower altitude plain regions of China. The current population structure and estimated past population dynamics suggest that the modern Beijing sublineage strains, which expanded over most of China and other global regions, did not show an expansion advantage in Tibet. The mutations in the Tibetan strains showed a higher proportion of A > G/T > C transitions than strains from the plain regions, and genes encoding DNA repair enzymes showed evidence of positive selection. Moreover, the long-term Tibetan exclusive selection for truncating mutations in the thiol-oxidoreductase encoding <i>sseA</i> gene suggests that <i>Mtb</i> was subjected to local selective pressures associated with oxidative stress. Collectively, the population genomics of <i>Mtb</i> strains in the relatively isolated population of Tibet provides genetic evidence that <i>Mtb</i> has adapted to local environments.