Characterizing Human-Pathogen Interactions and Natural Selection with Ancient DNA

Human health is determined by the interaction of physiological, ecological, social, and evolutionary factors. Over the next five years, the Amorim Lab will combine population genetics theory and genomic data analysis (from modern and ancient human samples) to understand the evolutionary forces behind human disease and adaptation. We will study the Black Death plague in the 15th century throughout Europe and the contact between Native Americans and Europeans. In both episodes, there were instances of strong selective pressure imposed by pathogens on the human host happening in a relatively short period of time. These features make these events ideal case-studies for developing new methods and theory to study natural selection using ancient DNA data, which up to now have rarely been used for characterizing natural selection in Homo sapiens. In part, this is due to the fact that the study of DNA from archeological samples faces several challenges, such as low endogenous DNA yield, among others. Future research in the Amorim Lab will build upon our experience in overcoming these challenges and in developing new analytical framework to study ancient DNA. One of the approaches we will take is to generate genomic data for large sample sizes through the screening of large numbers specimens from archeological sites in the relevant periods and geographic regions. Using these data we will (1) investigate how allele frequency changes in human populations are associated with the presence of lethal pathogens, (2) develop new methods to use these allele frequency changes to infer the parameters associated with the timing and strength of natural selection, (3) screen for novel ancient pathogens and identify the emergence of virulence factors in their genomes, and (4) characterize the determinants of the selective strength of new mutations in humans. Methods would take into consideration the demographic history of humans in order to disentangle its effects from those of natural selection being studied. The datasets we will generate will be an instrumental resource for the scientific community, which lack datasets with large sample sizes. The results of this project would advance evolutionary theory in regards to our understanding of natural selection and would allow for the characterization of human host-pathogen interactions according to a novel analytical framework. In addition, the results of this research would contribute for our understanding of past epidemics, the condition in which they emerged, and what facilitated their spread. The Amorim Lab is uniquely positioned to accomplish these goals because of our experience combining population genetics theory with the analysis of large-scale genomic datasets, in particular those from archeological specimens.