Date of Award

Spring 1-1-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Robin D. Dowell

Second Advisor

Ken Krauter

Third Advisor

Mark Johnston

Fourth Advisor

Greg Odorizzi

Fifth Advisor

Tom Blumenthal

Abstract

Polyploidy, or having more than 2 full sets of chromosomes, has occurred in the evolution of many fungi, plant, and animal species and is thought to contribute to speciation. Despite the important role of polyploidy in evolution, little is known about how polyploidy contributes to adaptation and speciation. We previously showed that tetraploid yeast adapted significantly faster to growth under carbon stress compared to the haploid and diploid yeast, yet it was not clear what mechanisms drove the increase in the rate of evolution in the tetraploid strains. To answer this, I assessed the different pathways of adaption that the haploid, diploid, and tetraploid yeast strains took to adapt to growth in raffinose medium. I examined the molecular mechanisms of adaptation utilized by the strains through whole genome sequencing and RNA expression analysis of over 100 evolved clones. The evolved clones gained adaptive mutations in a narrow set of genes involved in glucose sensing and uptake, however the higher ploidy strains gained significantly different types of mutations than haploid strains. Additionally, I demonstrate that a gene expression signature of just 5 genes can accurately predict the gene that carries an adaptive mutation in the evolved clone. While many of the adaptive mutations occur in genes that encode proteins with known roles in glucose sensing and uptake, I also discover mutations in genes with no canonical role in carbon utilization (IPT1 and MOT3) as well as identify novel dominant mutations in glucose responsive regulators thought to only accumulate recessive mutations in carbon limited environments (MTH1 and RGT1). I conclude that polyploid cells explore more genotypic and phenotypic space than lower ploidy cells. This is evidenced by a greater spectrum of beneficial mutations, including novel dominant alleles, copy number variation, and whole chromosome aneuploidy.

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