Understanding the Evolutionary Significance of Deleterious Genetic Variation

A Department of Computational Biology Seminar

Featuring Dr. Kirk Lohmueller, Professor, Department of Ecology and Evolutionary Biology, Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles

Many mutations that occur in genomes are deleterious, resulting in a decrease in reproductive fitness. In this talk, I will present our recent work on estimating fitness effects of deleterious mutations using genetic variation data from natural populations and explore the evolutionary consequences of deleterious mutations. First, I will present our results on inference of the distribution of fitness effects (DFE) for amino acid changes mutations in eleven animal species. We find that while the DFE differs across species, more phylogenetically similar species have more similar DFEs. Second, I will describe our recent work on finding models of dominance that are consistent with empirical genetic variation data. I will present estimates for amino acid changing mutations in Arabidopsis as well as humans. Third, I will attempt to validate population genetic models of selection by testing whether they predict observed levels of inbreeding load and match observed genetic data. Lastly, I will contrast patterns of genetic variation across the genomes of the California Chanel Island fox, the Isle Royale gray wolf, California sea otters as well as the critically endangered vaquita porpoise to better understand the mechanisms behind inbreeding depression. We use knowledge of dominance and the DFE in a forward-in-time simulation framework for genomic forecasting. Our work shows that populations that are currently small, but were historically large, are at greater risk from inbreeding depression than are populations which have been small or moderate size throughout their history. This work challenges paradigms in conservation biology that small populations are doomed to extinction.