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Abstract:Despite the fundamental roles of mutation as the driver of molecular evolution and the root of heritable diseases, much remains unknown about the germline mutational process, especially in humans. Whole-genome sequencing of pedigrees has enabled direct survey of newly arising mutations (i.e., de novo mutations) and updated our understanding of germline mutagenesis based on indirect approaches. My re-analysis of published human de novo mutations challenges the conventional view that DNA replication errors are the primary source of germline mutations in mammals and uncovers findings that support under-appreciated roles of DNA damage and maternal age in generating germline mutations. By relating the effects of parental ages on de novo mutations to the patterns of polymorphic variants in the population, I further investigate the role of the generation time in temporal variation in the human mutation spectrum and find evidence for increases in reproductive ages towards the present in human populations. Together, this work sheds new light on the germline mutational process and the evolution in mutation rate and spectrum in humans.
Ziyue is a postdoctoral scholar in Dr. Jonathan Pritchard’s lab in the Department of Genetics at Stanford, where she studies the roles of different evolutionary forces, such as demographic history and natural selection, in shaping human genetic variation. Before arriving at Stanford, she did her Ph.D. study in population genetics at University of Chicago, working with Dr. Molly Przeworski. In general, her research focuses on using computational approaches to address questions in human genetics in an evolutionary context, such as the impacts of natural selection on the human genome, the mechanisms and consequences of mutation rate variation, and the genetic basis and evolution of human disease.