Date:
Location:
Speaker:
Daniel Richard, PhD Candidate, HEB
Dissertation Abstract:
Modern-day humans enjoy an elongated lifespan relative to chimpanzees, even when accounting for environmental factors such as healthcare. This suggests that genetic changes to the biological processes underlying longevity have taken place over the course of human evolution, changes resultant from the forces of natural selection. The goal of this dissertation is to explore the potential means by which natural selection may have operated to shape the human genome, and the implications of genetic changes for the manifestation of ageing phenotypes – in particular, focusing on the incidence of late-onset diseases such as osteoarthritis. Over three data chapters, I will approach this goal in several ways: (1) considering the role for selection acting on development of a derived human trait in influencing the genetic risk for development of late-onset disease, (2) how shifts in epigenetic regulation over the course of development and aging influence the sequence properties and disease associations of genetic variants, and (3) how selection operating across long-lived species may act at the protein-coding level to alter the activity and function of aging-associated proteins.