Date of Award

2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Biology

First Advisor

Junhyong Kim

Abstract

Natural biological systems are resilient from the simplest form of unicellular organisms to the most complex form of multi-organ organisms. This resilience of a system manifests itself in two ways: "returns to its current attractor or moves to a new attractor that maintains the system's functions" (Hiroaki Kitano, 2004). That is, a system can work to maintain its current state or change to a new state that allows it to properly function under perturbations. One such complex system is the regulation of gene expression in biological organisms in which recruitment of transcriptional machinery to gene regulatory regions activates and controls transcription of target genes. Systemic responses of gene expression to perturbations result in alteration or stability of gene expression in individual genes as well as the state of cellular functions.

The objective of this work is to investigate the consequences of temperature perturbation on genome-wide gene expression with respect to cellular growth in two contrasting attributes: variation and robustness. We first characterize variation of genome-wide gene expression across five temperature conditions in three Saccharomyces cerevisiae strains--two natural strains and one laboratory strain--and investigate potential regulatory mechanisms of this expression variation. We show that as many as half of the number of genes in the genome exhibit expression variation but this gene expression variation is mostly specific to each strain. However, the global transcriptome displays a simple linear response to the temperature gradient manifested as a one-dimensional subspace, suggesting a global coordination of transcription against temperature perturbation.

Next, we characterize the robustness of genome-wide gene expression against temperature perturbation and compare it against the genetic differences in gene expression among these three strains. We provide evidence to support a hypothesis that selective forces potentially drive congruent evolution of genetic and temperature robustness of genome-wide gene expression. We present results to support the hypothesis that greater selection for gene expression robustness against temperature perturbation occurs in the natural strains compared to the laboratory strain, and that the evolution of gene expression robustness likely involves trans-factors.

In summary, we propose that a global regulatory coordination of transcription via trans-factors likely modulates genome-wide gene expression in relation to growth-permissive perturbations and drives congruent evolution of genetic robustness in the unicellular eukaryote, Saccharomyces cerevisiae.

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