Mycobacterium tuberculosis is an obligate human pathogen. However, our understanding of the MTB biology in humans is limited by the difficulty of accessing the sites of infection. Bacterial population genetics provides mechanistic insights into the biology of MTB in people. We have leveraged MTB population genetics to identify genes that are evolving to increase the bacterium’s ability to survive drug pressure. This analysis has revealed a novel regulatory circuit governing the integration of chromosomal replication and cell division. Genetic variation in the circuit components alters cell cycle and the ability to restart growth after antibiotic stress.