Years of trait mapping studies have uncovered the genetic determinants underlying phenotypic evolution over both short and long timescales in a variety of organisms.

A more general understanding of the mechanisms through which evolution produces phenotypic novelty, however, still remains out of reach. Many outstanding questions remain, among them how coding sequence divergence and gene expression divergence respectively contribute to trait evolution, as well as what role rare and large effect genetic variants play in the genetic networks underlying evolving phenotypes. Using Saccharomyces yeast as a genetically tractable model system in which to probe these questions, we identify and dissect several examples of trait divergence within and between yeast species. We first investigate an instance of intraspecific variation among yeasts isolated from a single population, finding that large effect rare variants at hypermutable loci are drivers of many common morphological and growth phenotypes. Next, in a comparison of both recently-diverged and long-diverged species, we investigate the role that gene expression variation plays in phenotypic evolution. We find evidence in multiple gene networks for complex and coherent regulatory evolution, and in one instance we succeed in identifying the loci that effect this change, as well as several phenotypic novelties they produce. Collectively, these investigations will contribute to the growing body of literature that describe the genetic mechanisms that underlie phenotypic change and seek, eventually, to achieve a greater understanding of basic evolutionary principles.