The exchange of pathogens between humans and other animals has been longstanding, and recent examples include HIV, SARS, flu viruses, and Yersinia pestis (which causes the plague). Today, especially in the developing world, humans and their domesticated animals continue to encroach upon wild animal habitats, with opportunities for cross-species transmission (or "spillover") expanding as exposure increases. This project will provide insight into the process by which pathogens adapt to new hosts and the impact of human migration and interaction on the spread of pathogens in the past. In particular, the project will use ancient DNA and skeletal analyses to investigate how human migration events and possible changes in virulence of M. tuberculosis strains have facilitated the spread of tuberculosis (TB) during human evolutionary history, with specific hypotheses about how tuberculosis may have been transmitted from animals to humans, and from the Old World to the Americas. A better understanding of the evolutionary history of mycobacteria such as those causing TB and leprosy can provide insights for other researchers interested in developing clinical treatments. Because human TB (and its descendants) has had a profound impact on other species, it is thus also a conservation concern. During this project, both undergraduate and graduate students will be trained in molecular techniques and data analysis. The data generated will be deposited in public databases such as GenBank, and the results of data analyses will be published in scholarly articles as well as in formats accessible to the general public.
This project will identify, document, and sample 285 remains with skeletal lesions characteristic of TB that date to before and after European contact in the Americas. Newly developed methods will then be used to extract DNA from these samples, as well as to target and sequence the ancient pathogen genomes. We have assembled a team of experts in ancient DNA, bioarchaeology, bioinformatics, and population genetics to address two specific aims. The first is to examine the geographic patterning of pathogenic mycobacteria, particularly M. tuberculosis complex (MTBC), in the Americas through time. Specifically, we will test whether prehistoric TB in Peru and South America were the result of a single jump of M. pinnipedii into humans, if prehistoric TB in North America was caused by MTBC strains that are most closely related to M. pinnipedii strains found in ancient South Americans, and whether strains found in specimens with atypical skeletal pathologies from pre-contact Mexico are M. lepromatosis (a newly discovered strain of mycobacteria that causes atypical leprosy). The second aim is to discern signatures of adaptation to humans by mycobacteria through time. For this aim, we will test the hypotheses that 1) the zoonotic M. pinnipedii strain(s) that "jumped" into humans in South America shows signs of selection that indicate adaptation to this new host and 2) local mycobacterial strains in the Americas were replaced by more virulent strains at contact over a relatively short time period (ex: following contact/increased trade in the New World). The genome data obtained from the ancient samples along with comparative data from modern strains will be used to construct phylogenies of these pathogens, to assess patterns of diversity across the Americas (and through time), and to test for signals of selection. The pattern of adaptation of the MTBC and other mycobacteria in humans over time is of interest since it helps understand the success of these organisms and their possible future trajectories.
