Professor Patricia Wittkopp was awarded a grant of just over $1.15 million from the National Institutes of Health for her research on the evolution of gene expression in yeast. Her work will shed light on properties of mutations that lead to genetic variation for evolution and disease.

New mutations (changes in DNA sequence) arise naturally in all living things. Some have no effect, some are beneficial, and some are deleterious, including those that lead to disease states such as cancer. The fate of these mutations after they arise is determined to a large extent by natural selection. Currently, we know much more about how natural selection changes the frequency of new mutations than we do about the effects of new mutations that generate the variation upon which selection acts. This grant aims determine how mutation and selection shape patterns of diversity seen in natural populations. Specifically, Wittkopp’s research will focus on mutations that affect how a gene is turned "on" or "expressed.”

“Heritable differences in gene expression are common and contribute to phenotypic diversity between species, between individuals of the same species, and sometimes even between cells of the same individual,” Wittkopp said. “This diversity includes ‘normal’ variation among healthy individuals as well as ‘abnormal’ variation causing disease. Despite their importance, the genetic changes responsible for difference in gene expression and the evolutionary processes that affect them are not well understood.

“This project will help fill this knowledge gap by (1) collecting and characterizing new mutations affecting expression of a focal gene, (2) identifying and characterizing mutations segregating within a species, and (3) determining how properties of these mutations affect fitness in natural populations. 

“Using this information, we will determine what makes some mutations more likely to survive in the wild than others and also incorporate the effects of mutations into models of evolution. These models are important not only for understanding how species change over time, but also for understanding how new mutations and selection among cells interact during tumor formation in cancer patients."

Working on the project with Wittkopp are: graduate students Brian Metzger (EEB), postdoctoral fellows Andrea Hodgins-Davis and Fabien Duveau, and Elizabeth Walker, lab manager/technician. The project period for the grant is September 2013 – May 2017.