Dr. Kirk E. LohmuellerDepartment of Ecology and Evolutionary BiologyUCLAWhy do deleterious mutations persist in populations?Many mutations that arise in protein coding regions of genes are deleterious, resulting in a decrease in reproductive fitness. While such mutations are often eliminated from the population by natural selection, sometimes they can remain. In this talk I will examine the population genetic factors leading to the accumulation of deleterious mutations. First I will use Wright-Fisher population genetic simulations to show how recent demographic history has affected patterns of deleterious variation across different human populations. Second, I will present an analysis of deleterious genetic variation across dog and wolf populations using more than 80 genomes. I will describe a maximum likelihood approach to estimate heterozygosity from next-generation sequencing data that we used on these low-coverage genomes. These data show that the ratio of amino-acid changing to silent genetic variants is significantly higher in dogs than wolves, suggesting that, compared to the reduction of neutral levels of variation, less deleterious variation has been removed than expected. Finally, I will show how the artificial selection for specific traits during domestication and breed formation has affected patterns of deleterious variation in dogs. In sum, this work demonstrates how population history and strong positive selection can shape deleterious variation across genomes.