UCLA

A central question in genetics asks how genetic variation influences phenotypic variation. The distribution of genetic variation in a population is reflective of the evolutionary forces that shape and maintain genetic diversity such as mutation, natural selection, and genetic drift. In turn, this genetic variation affects molecular phenotypes like gene expression and eventually leads to variation in complex traits. In my dissertation, I develop statistical methods and apply computational approaches to understand these dynamics in human populations. In the first chapter, I describe a statistical model for detecting the presence of archaic haplotypes in modern human populations without having access to a reference archaic genome. I apply this method to the genomes of individuals from Europe and find that I can recover segments of DNA inherited from Neanderthals as a result of archaic admixture. In the second chapter, I apply this method to the genomes of individuals from several African populations and find that approximately 7\% of the genomes are inherited from an archaic species. Modeling of the site frequency spectrum suggests that the presence of these haplotypes is best explained by admixture with an unknown archaic hominin species. In the final chapter, I focus on the more recent history of humans and the genetic architecture of complex traits. In particular, I find that a substantial portion of the genetic architecture is population specific, which limits our ability to transfer phenotype predictions across populations.