One of the most pressing challenges facing medical researchers and evolutionary biologists alike is determining which changes in DNA sequence underlie particular phenotypes and how they exert their effects. This is especially true for changes in noncoding regions, many of which affect gene expression. Research in the Wittkopp lab investigates the genetic and molecular mechanisms underlying phenotypic differences and examines the evolutionary processes by which they came to be. This includes differences among cell types, among individuals, and among species. The transcriptional regulation of gene expression is emphasized in this work because of its key role in converting genotypes into phenotypes.

We employ a variety of research techniques to address these issues. Current students and postdoctoral researchers have expertise in molecular biology, developmental genetics, population genetics, quantitative genetics, evolutionary biology, computational biology, ecology, and/or statistics, with most lab members having (or developing) expertise in many of these areas. As a group, we are committed to identifying compelling research questions, developing creative ways to address them, and learning (or inventing) whatever techniques are needed to make this happen.

Currently, we are using multiple Drosophila species as well as the baker’s yeast Saccharomyces cerevisiae to address four complementary questions:

  1. What are the genetic and molecular mechanisms underlying phenotypic differences within and between species and how did they evolve?
  2. How do cis-regulatory sequences determine gene expression and how does the architecture of cis-regulatory regions change over time?
  3. What are the relative contributions of cis- and trans-regulatory changes to expression differences genome-wide and how does natural selection shape their evolution?
  4. What are the functional properties of new mutations and how do they influence which mutations segregate within a species and become fixed between species?

The first two of these projects are single-gene, mechanistic studies whereas the latter two are broader investigations into gene regulation and phenotypic diversity on a genomic scale.