Deciphering The Evolutionary and Biological Impact of Human Admixture

Project Summary Admixture is a vital evolutionary process that profoundly shapes human genetic diversity and health. Current evidence suggests that admixture is ubiquitous throughout human evolution and has been accelerating during our recent evolutionary history. However, despite the paramount importance of admixture, we still lack sufficient means to infer a complete admixture history in humans. Due to the underrepresentation of non-European populations in biobanks, we also do not fully understand the genetic basis of complex traits in admixed populations. Furthermore, constrained by our long generation time, we do not have a holistic view of how admixture interacted with other evolutionary processes such as selection, and how they shaped genomes over time. Synthesizing computational methods development and empirical population genomics, my lab will decipher the evolutionary history and biological impact of human admixture via three lines of work. First, we will develop machine learning methods to investigate some of the oldest admixture events, the archaic introgression, in understudied non-European populations. Specifically, we will search for evidence of introgression with unknown, “ghost” hominins in East Asians, and leverage the evolutionary trajectory of adaptive introgression gene regions to infer a comprehensive population history for South Americans. Next, we will focus on the impact of recent admixture in shaping complex traits in modern humans. We will use simulations to model changes in the underlying genetic architecture of complex traits caused by admixture and develop novel statistical methods to improve the accuracy of complex trait phenotype predictions in populations that experienced recent and ongoing admixture. Finally, we aim to elucidate the real-time process and functional consequences of admixture using two nonhuman study systems with shorter generations. We will use interbreeding Drosophila species to experimentally track the dynamics between admixture and selection on admixed genomes over time. We will couple the work with an admixed captive colony of rhesus macaques that has longitudinal records of genomic and phenotypic data to investigate how admixture changes individual fitness and phenotypes directly relevant to humans. Overall, this research will provide invaluable empirical evidence and powerful quantitative tools to enhance our understanding of human admixture from complementary perspectives.