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Title

The Phenotypic Effects of Non-Neutral Sequence Evolution in FZF1 and ZRT1

Date of Award

Summer 8-15-2012

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

Dissertation

Abstract

Determining the genetic basis of evolutionary changes that have led to phenotype differences within and between species is challenging. Yet, success can lead to important insights into the genetic basis of adaptation and the molecular basis of species' differences. An effective means of identifying genes underlying phenotypes of interest is genetic mapping, but mapping approaches are constrained to alleles of large effect and known phenotypes. In contrast, a population genetics approach identifies genes with adaptive sequence evolution through tests of selection, rather than by specific phenotypes. This approach can identify genes with many small effect mutations and can lead to the discovery of novel phenotype differences. Despite tests of selection suggesting the presence of numerous adaptive substitutions, genes identified through tests of selection are rarely tested for phenotype differences.

In this work I use a population genetics based approach to identify genes that contribute to phenotype divergence. First, I use a genome-wide scan for selection in noncoding regions and identify the transcription factor FZF1. I find that FZF1 has evolved differences between species in both its expression pattern and in its ability to confer sulfite resistance. The phenotype difference is a result of multiple coding and noncoding changes. Second, I use genome-wide scans for adaptation in coding regions and identify the gene ZRT1, a zinc transporter. I show that ZRT1 has excess polymorphism within species, suggesting the presence of balancing selection. ZRT1 alleles confer no phenotype differences under the conditions measured. However, I show that high amounts of nonsynonymous and synonymous polymorphism strongly support that ZRT1 has been under balancing selection. This observation raises the possibility that genome-wide estimates of adaptive evolution in yeast may be confounded by balancing selection. The results of this thesis demonstrate that population genetic tests of selection can be used to identify genes involved in novel phenotype differences between species and provide insight into the genetic basis of the differences.

Language

English (en)

Chair and Committee

Justin Fay

Committee Members

Tim Schedl, Barak Cohen, Ken Olsen, Heather True-Krob, Gautam Dantas

Comments

Permanent URL: https://doi.org/10.7936/K7XK8CGB

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