Inter-species genetics using the Saccharomyces yeast
Saccharomyces cerevisiae is the dominant model organism of eukaryotic microbiology. Research in the lab expands the power of these tools by extending them to distantly related Saccharomyces species. In addition, while Saccharomyces species are reproductively isolated, they can readily form viable hybrids and can be manipulated to produce viable meiotic progeny. As a result, genetic mapping, reciprocal hemizygosity tests, and the mechanisms of regulatory divergence can readily be identified across species as different as human and chickens. This creates a uniquely powerful system for dissecting the genetic basis of trait differences between distantly related species.
Evolution of Gene Regulation
Having the correct molecular tools is useless to an organism unless those tools are employed in the appropriate amounts and at the appropriate times. As a model for the evolution of novel molecular function, our research focuses on dissecting changes in gene expression and regulation. We use high-throughput flow cytometry and next generation RNA sequencing to identify both the molecular basis for specific changes in regulation and genome wide patterns of regulatory divergence.
Replaying the Tape of Life
The evolution of most molecular functions occurs but a single time in history. As such, we often know very little about the mechanisms necessary for the emergence of new functions. We use ancestral state reconstruction, single-locus experimental evolution, and statistical genetics, to explore alternative paths by which historically novel functions may have evolved if given a second chance. By replicating ancient changes in regulation within the laboratory, this approach allows the general genetic and molecular mechanisms underlying the emergence and evolution of novel traits to be determined by comparative methods.
The Role of New Mutations
New mutations are the ultimate source of novel phenotypes and the raw material of evolution, determining the magnitude and frequency at which new phenotypic diversity is available to evolution. By comparing the effects of new mutations to the effects of variants found in natural populations, a powerful test for the action of natural selection can be formed. We are one of the pioneers of this approach for the study of regulatory evolution, and use it to identifying both the relative contributions of mutation, selection, and drift to patterns of variation across regulatory elements and the targets of natural selection.