Abstract: Genetic variation affecting gene expression is wide-spread within and among species. This variation reflects the combined actions of mutation introducing new genetic variants and selection eliminating deleterious ones. Comparative studies of gene expression in fruit flies, yeast, plants, and mice have shown that the relative contributions of cis- and trans-acting variants to expression differences change over evolutionary time, indicating that selection has different effects on cis- and trans-regulatory variants. To better understand the reasons for this now widely observed pattern, we have been systematically studying the effects of mutation and selection on expression of the TDH3 gene of the baker’s yeast Saccharomyces cerevisiae. This work has revealed differences between cis- and trans-regulatory mutations in their frequency, effects, and dominance. Differences in pleiotropy are also generally assumed to exist between cis- and trans-regulatory that affect their evolutionary fate, but have been difficult to measure. In this talk, I will discuss how newly arising cis- and trans-regulatory mutations affecting expression of this focal gene are structured within the regulatory network, their pleiotropic effects on expression of all other genes in the genome, and how these pleiotropic effects influence fitness. A computational model of regulatory evolution integrating empirically observed differences in properties of cis- and trans-regulatory mutations will also be presented and discussed.
Short Bio: Patricia Wittkopp received a BS from the University of Michigan, a PhD from the University of Wisconsin, and did postdoctoral work at Cornell University. In 2005, she began a faculty position at the University of Michigan, where she is now the Sally L. Allen Collegiate Professor and Arthur F Thurnau Professor in the Department of Ecology and Evolutionary Biology and the Department of Molecular, Cellular, and Developmental Biology, and is a member of the Center for Computational Medicine and Bioinformatics. Her research investigates the genetic basis of phenotypic evolution, with an emphasis on the evolution of gene expression. She was a Damon Runyon Cancer Research Fellow, an Alfred P Sloan Research Fellow, Guggenheim Fellow, and a recipient of a March of Dimes Starter Scholar Award, the Margaret Dayhoff Mid-Career Award from the Society of Molecular Biology and Evolution, and the Friedrich Wilhelm Bessel Research Award from the Alexander von Humboldt Foundation.