Dysfunctional Gene Regulation of the Meiotic Program in an Interspecific Yeast Hybrid

Speciation, the evolutionary process by which species arise, is a fundamental biological concept. One of the major goals of evolutionary genetics is to understand the genetic basis of reproductive isolation (RI), a collection of barriers that prevents two species from forming viable or fertile hybrids. Given the lack of viable or fertile hybrid progeny, identifying genes that impact RI as well as their functions has been difficult. Thus we lack a view of the total genetic contribution to RI. Recently the budding yeast Saccharomyces has served as an evolutionary model, as abundant sequence, expression, and phenotypic data exist for the model organism S. cerevisiae and its closest relatives. Additionally we can manipulate the yeast genome and control its environment arguably more than any other organism. Hence I developed assays to catalog all genes contributing to RI between S. cerevisiae and its closest known relative S. paradoxus, which can form sterile hybrids under laboratory conditions. Chapter 2 details my utilization of accessible genetic tools for yeast to understand the total contribution of genes to RI. Though I unveiled multiple problems with studying speciation genetics using standard methods in yeast, I acquired valuable information about the biology of hybrids. For instance, I determine that yeast hybrids are highly sensitive to background mutations, commonly generated in yeast transgenesis, resulting in experimental artifacts. Using this knowledge, I took advantage of the emergence of next-generation sequencing in Chapter 3 to analyze wild type hybrid and parental genome expression to understand the relationship between gene expression and RI. My main objectives in my dissertation are to understand dysfunctional hybrid gene regulation in the context of RI in yeast and to ascertain subsets of genes whose expression is disrupted. Thus I measured genome-wide changes in gene expression over the course of meiosis for S. cerevisiae, S. paradoxus and their sterile hybrid. I show that misexpressed genes in a yeast hybrid result from earlier activation of the meiotic program relative to its parents. This heterochrony is expected under the anti-recombination model of RI in yeast. I also find an increase in dysfunctional regulation in genes that are involved with sporulation, mitochondrial function, rRNA processing and translation. Genes in these pathways could contribute to RI. My dissertation adds to the field of speciation genetics, as it lends an example of a time-dependent relationship between dysfunctional hybrid regulation and RI for yeast species, as well as identifies candidate genes that could contribute to RI