Tuberculosis (TB) is a re-emerging infectious disease with a global history extending over 3 million years in the Old World and originating in Africa. Recent research in molecular genetics confirms what paleopathologists have long suspected - that Mycobacterium tuberculosis was pathogenic for ancient Americans long before late 15th century European contact. The goal of this project is to analyze DNA from ancient strains of M. tuberculosis in both the New World and Old World to understand their relationship to modern strains, thus addressing questions about the evolutionary history of TB. Specifically, the PIs propose to characterize strains from the earliest Old World skeletal cases of disseminated TB, explore the relationship of these early strains to those found in Britain by Iron Age/Roman times, consider the relationship between Old and New World TB prior to and following the 16th century era of European Exploration, and assess whether the increase in prevalence of tuberculosis during the 17th and 18th centuries in Europe was due to the spread of new strains.
The scientific merit of this study is that will expand previous ancient DNA work by focusing on DNA sequences containing informative nucleotide changes that indicate strain/lineage affiliations and relationships. The results will be used to address the hypotheses that prehistoric TB in the Americas was caused by M. tuberculosis strains that are most closely related to modern strains found in Asia and that new strains of M. tuberculosis, most closely related to those prevalent today in Europe, were introduced at European contact. In European samples, the hypothesis that the increase in prevalence of tuberculosis in Europe during the 17th and 18th centuries was due to new strains that were the same as those introduced into the Americas will be tested. In the long term, this project is designed to establish ancient global strain patterning, history of the disease, pattern of virulence, and relationships with other mycobacteria such as M. leprae and M. bovis. This work will focus first upon temporal and geographic coverage, centering upon the spread of the disease through human migration events and characterizing the evolution of M. tuberculosis in relationship to human evolutionary history.
The broader impact of this project is that it will provide a unique viewpoint into the evolution of M. tuberculosis and could provide insights valuable to researchers seeking an understanding of the biology of the organism and developing new vaccine strategies. This project will also involve graduate and undergraduate student training in laboratory methods and analyses. Finally, in addition to disseminating results in scholarly articles, we will include information about the project that is accessible to the general public in English and Spanish on the laboratory website (www.public.asu.edu/~acstone/lab/molecular_anthropology_lab.htm).
