4 Field Colloquium: "Tuberculosis and leprosy: origins, migration, and exchange in humans and other primates"

Mycobacterial diseases, including tuberculosis (TB) and leprosy (or Hansen’s disease), have profoundly altered the course of human history. Yet our knowledge of the temporal evolutionary dynamics for these pathogens is remarkably limited, despite their importance for identifying links between the pathogens and signatures of adaptation in the human genome as well as for predicting future trends in the pathogen-host interaction. Here I examine the evolutionary history of tuberculosis and leprosy, focusing on the distribution of strain diversity in humans (past and present) and non-human primates in order to elucidate phylogenetic relationships, examine signals of adaptation to humans, identify the impact of human demography on their spread, and assess patterns of pathogen exchange through time. Specifically, we use new methods of DNA extraction, library construction, and targeted enrichment to obtain genetic data from prehistoric samples with characteristic lesions of mycobacterial disease. To date, we have assessed mycobacterial preservation in over 140 samples, and after using array capture, we sequenced the complete M. tuberculosis genome from three ancient Peruvians dating to ~1000 years ago. Our analyses indicate that in the Americas, M. tuberculosis likely “jumped” from pinnipeds (seals and sea lions) that brought the pathogen from Africa within the last 2000 years. In addition, using these ancient genomes to calibrate the molecular clock, we find that TB likely became a human pathogen within the last 6,000 years. Finally, we are also applying similar methods to surveys of modern primate populations and show the presence of these mycobacteria, suggesting that the exchange of these pathogens among species has important public health and primate conservation implications.