High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography

TLDR

Mycobacterium tuberculosis infects a third of the global population and causes a death every 15 seconds, yet human‑adapted strains have long been assumed to be essentially identical despite clear distinctions from animal‑adapted members. We surveyed sequence diversity within a global collection of MTBC strains using seven megabase pairs of DNA sequence data. The analysis reveals that human‑adapted MTBC strains are far more genetically diverse than previously thought, with diversity tied to human migration, reduced purifying selection, and heightened genetic drift, potentially driving the emergence and spread of drug‑resistant tuberculosis.

Abstract

Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.