Chagas Disease in the ancient Americas: Investigating past to present human parasitism through the molecular and archaeological record

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The Directorate of Social, Behavioral and Economic Sciences offers postdoctoral research fellowships to provide opportunities for recent doctoral graduates to obtain additional training, to gain research experience under the sponsorship of established scientists, and to broaden their scientific horizons beyond their undergraduate and graduate training. Postdoctoral fellowships are further designed to assist new scientists to direct their research efforts across traditional disciplinary lines and to avail themselves of unique research resources, sites, and facilities, including at foreign locations. This postdoctoral fellowship trains an interdisciplinary scientist exploring the evolutionary and anthropogenic processes associated with the emergence of Chagas Disease in the Americas.Chagas Disease (CD) is caused by a New World parasite that has infected humans since our earliest migrations into the Americas c. 15,000 years ago. Today the causative agent, Trypanosoma cruzi, infects millions of people, primarily in Latin America. CD presents a new global challenge as its continual spread, facilitated by climate change and human activity, threatens non-endemic countries, causing 300,000 infections in the US alone. While treatment is available for acute infections, the chronic form can result in cardiac and digestive organ failure. The clinical manifestations have been recognized in archaeological human remains from South America as early as 9,000 years ago. Despite the increase of available genetic data, the evolutionary history of T. cruzi and the timing of the emergence of Chagas Disease remain unresolved. This project applies novel paleogenomic methods to target T. cruzi in human remains found in pre-Columbian South America to test hypotheses regarding the origins, timing and dispersal of human-adapted lineages. More critical for contemporary society, the research team also explores the anthropogenic (i.e. human behavior, landscape use, social structure, subsistence) and natural (i.e. climate change) factors associated with the emergence and persistence of CD in the Americas. Interdisciplinary collaboration and training from both life and social sciences, including computational biology, is critical for success. All sequence data generated during the research will be deposited on public databases, broadly accessible to students, clinical researchers and the greater scientific community. Results will be disseminated in peer-reviewed journals, at professional meetings, and within the classroom and community, providing the fellow with additional opportunities to continue her participation in outreach and educational programs that promote young women in science. By providing direct access to the genetic signatures of past human infection, we promote a "deep-time" approach to contemporary issues of local and global health.The proposed project synthesizes bioarchaeological, molecular and ecological evidence to examine the origins and dispersal of T. cruzi and illuminate the evolutionary and anthropogenic processes associated with the emergence of Chagas Disease in the Americas. While previous paleogenetic analyses of CD offer limited genetic and phylogenetic information, analyses of complete ancient pathogen genomes capable of addressing the proposed questions are now possible following the application of DNA enrichment and high-throughput sequencing to archaeological or historic samples. This project represents the first genome-scale study of ancient CD. In the dedicated cleanroom at the UCSC Human Paleogenomics Lab, "next-gen" methods are applied to an extensive, well-contextualized collection of archaeological human remains from pre-Columbian South America, including samples identified with clinical signs of CD. For each individual, a unique DNA sequencing library is constructed immediately following DNA extraction from the bone, tooth or tissue. The process of library construction effectively transforms samples into renewable resources; "immortalized" libraries can perpetually be re-amplified and thus repurposed for new experiments and shared with other researchers. Pathogen DNA often represents less than 0.1% of endogenous molecules in a library; enrichment methods are employed to target and capture only sequences of interest, radically improving the likelihood of recovering T. cruzi DNA. The research team uses the latest computational methods capable of confronting next-generation data from highly damaged, degraded DNA fraught with sequencing errors, helping us to establish authenticity, and producing high quality output to use in evolutionary analyses. With calibration points derived from the time-stamped sequence data, they can estimate mutation rates, reconstruct phylogenies alongside publicly available modern T. cruzi DNA with methods that integrate heterochronous data, and date divergence events used to test current hypotheses regarding the evolution of human-adapted T. cruzi. With the addition of paleoecological records and the archaeological context of the past several millennia in the New World, the Fellow aims to provide a diachronic perspective on the paleoepidemiological patterns of CD in the face of changing cultural and environmental conditions.