Date of Award

Winter 12-15-2018

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type



The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is relatively heat tolerant, whereas S. uvarum is heat sensitive but outperforms S. cerevisiae at 4 degree C. Gene expression analysis with an S. cerevisiae and S. uvarum hybrid revealed a small set of 136 genes with temperature-dependent cis-acting differences, suggesting that the temperature divergence has not caused widespread cis-regulatory divergence. Using a genome-wide non-complementation screen, I found a single nuclear-encoded gene with a modest contribution to heat tolerance, and a large effect of the species' mitochondrial DNA (mitotype). Recombinant mitotypes and allele replacements indicate multiple mitochondria-encoded genes contribute to thermal divergence, with the coding sequence of COX1 showing a moderate effect on both heat and cold tolerance. The non-complementation approach also identified allele differences of CUP2, a copper-binding transcription factor, in copper resistance of S. cerevisiae and S. uvarum. Chimeric alleles showed that multiple changes underlie the resistance of S. cerevisiae CUP2, with cis-regulatory changes having a larger effect than coding changes. Taken together, my findings suggest that evolution of interspecific phenotypic differences often involves accumulation of small-to-medium effect changes, such as those in mitochondrial DNA and CUP2, and can occur through both coding and cis-regulatory changes.


English (en)

Chair and Committee

Justin C. Fay

Committee Members

Yehuda Ben-Shahar, Barak A. Cohen, Kenneth M. Olsen, Heather L. True-Krob,


Permanent URL: https://doi.org/10.7936/ap0p-a573