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Ancient American Tuberculosis: Origin(s), Spread & Replacement

Sea lion on rocks

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. Researchers will test the hypothesis that prehistoric TB in the Americas was caused by strains in the M. tuberculosis group or complex (specifically strains found in seals and sea lions) that “jumped” into humans and then spread from human to human, moving north from South America into Central and North America via trade routes.

This research will 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.

Using new methods of ancient DNA analysis, the researchers will test the hypothesis that prehistoric TB in the Americas was caused by strains in the M. tuberculosis group or complex (specifically strains found in seals and sea lions) that “jumped” into humans and then spread from human to human, moving north from South America into Central and North America via trade routes.

The ancient genome data will also be used to test whether there is clear evidence that seal strains “jumped” into humans once or multiple times and to assess whether contact period strains from Europe, which may have been more virulent, replaced the pre-contact strains quickly (within one or two hundred years) or slowly.

Moreover, these data will be used to discover whether additional TB strains were brought into North America from East Asia with the expansion of Inuit/Aleut ancestors or from Europe via contact with the Norse.

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 domesticates 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, a better understanding of the evolutionary history of mycobacteria such as those causing tuberculosis 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 tuberculosis 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 these organisms’ success and possible future trajectory.

Related LInk:
Stone Laboratory: The Evolutionary History of Tuberculosis and Leprosy

 

Funding Source:
National Science Foundation 

Anne C. Stone, Arizona State University School of Human Evolution and Social Change
Jane Buikstra, Arizona State University School of Human Evolution and Social Change
Michael Rosenberg, Arizona State University School of Life Sciences
Johannes Krause, Max Planck Institute for the Science of Human History
Kirsten Bos, Max Planck Institute for the Science of Human History