The evolutionary timing and spread of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains largely unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we show that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from humans and the other composed of both animal and human isolates.
The latter also likely derived from a human pathogenic lineage, supporting the hypothesis of an original human host. Using Bayesian statistics and experimental data on the variability of the mycobacterial markers in infected patients, we estimated the age of the MTBC at 40,000 years, coinciding with the expansion of “modern” human populations out of Africa. Moreover, the diversification of the oldest EAI and LAM populations took place during plant and animal domestication.
In the Fertile Crescent, 13,000 years ago, small nomadic hunter-gatherer groups were replaced by farming societies based on domesticated livestock and crops. This paramount event in human history was probably not without consequence for an epidemic, infectious disease such as tuberculosis, where crowded farming populations may have promoted high infection rates, bacterial spread and transition to new niches and animal hosts.
Furthermore, coalescence analysis revealed a strong and recent demographic expansion in almost all M. tuberculosis lineages, which coincides with the human population explosion over the last two centuries. These findings thus unveil the dynamic dimension of the association between human host and pathogen populations.
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