Out-of-Africa migration and Neolithic co-expansion of Mycobacterium tuberculosis with modern humans

Tuberculosis caused 20% of all human deaths in the Western world between the 17th and 19th centuries, and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. Here we used 259 whole-genome sequences to reconstruct the evolutionary history of the Mycobacterium tuberculosis complex (MTBC). Coalescent analyses indicate that MTBC emerged about 70 thousand years ago, accompanied migrations of anatomically modern humans out of Africa, and expanded as a consequence of increases in human population density during the Neolithic. This long co-evolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low- and high host densities.