Project summary The long-term goal of this project is to understand the genetic mechanisms and evolutionary processes responsible for generating phenotypic diversity within and between species. This includes discovering the genes responsible for phenotypic divergence, identifying which changes within these genes affect the phenotype, and determining how these changes alter molecular, cellular, and developmental processes. It also includes figuring out how mutation and selection have worked together to give rise to these changes. These goals will be accomplished by combining methods from developmental biology, evolutionary genetics, genomics, and bioinformatics to study both fruit flies (Drosophila) and yeast (Saccharomyces). Specific experiments proposed are designed to address the following three complementary questions: (1) What are the genetic and molecular mechanisms underlying phenotypic differences? (2) How do regulatory networks composed of cis- and trans-acting factors controlling gene expression evolve? and (3) What are the relative contributions of mutation and selection to variation in gene expression? Taken together, this work will advance our understanding of genotype-phenotype maps and how they vary within and between species. Genetic changes affecting the regulation of gene expression, an essential step in translating genotypes into phenotypes, will be given particular emphasis in this work. Ultimately, lessons learned from these studies will contribute to a general framework for predicting and interpreting patterns of genotypic and phenotypic variation, including variation related to human health.