Doctoral Dissertation Research: Ancient Genomics and the Molecular Mechanisms of Human Tolerance to Arsenic

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Arsenic causes severe toxicological effects in humans, yet some human populations have evolved to tolerate this element. Today, people in some regions may carry protective mutations in a key enzyme that metabolizes arsenic in the liver. However, several aspects remain unclear about the evolutionary history and genetic basis of arsenic tolerance. This doctoral dissertation research project therefore examines the genetic history, modes of subsistence, and gene regulatory mechanisms in ancient and modern DNA samples from populations exposed to arsenic. The findings can expand our understanding of biocultural processes through which humans are able to adapt to their environment. The project also supports student mentorship and training opportunities for undergraduate and graduate students, opportunities for international research collaborations, and science dissemination through conferences and social media.This project is centered on the understanding of the cultural and biological diversity of ancient and modern populations living in an arsenic rich region. Specifically, three main questions are addressed: (1) what are the genetic history and relationships among ancient and modern populations? (2) how did the transition to agriculture impact diet and oral health? and (3) what role/function do the mutations associated with arsenic tolerance play in the expression of the AS3MT gene? The researcher reconstructs the genetic prehistory of the region using ancient DNA and modern genomic data. In addition, oral microbiome data from ancient dental calculus are used to characterize the prehistoric diet, oral health and environmental exposures among pre-agricultural and agricultural populations. Third, genetic sequences carrying protective mutations are used to assess experimentally whether they alter/regulate the expression of the AS3MT gene in vitro.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.