Uncovering Genes Underlying Quantitative Trait Variation Using S. cerevisiae as a Model System

Abstract

Individuals from the same species often differ quantitatively in many phenotypes. Understanding the genetic causes of such individuality may improve our understanding of the corresponding phenotypes, and our ability to make models to predict phenotypes using individual's genotype. In this thesis, I would like to present two works related to this question. In Chapter 2, I used a few highly sensitive experimental systems to ask, what are "all" the genes that can affect a given quantitative trait. By analyzing these results, I found that a large number of yeast genes can affect four studied traits, namely two galactose response traits, unfolded protein response and growth rate in rich medium. These genes consist of a few large effect-size genes that are typically directly involved in the process related to the quantitative trait, and a large number of small effect-size genes that are enriched in a number of core cellular processes. This implies that genetic variation in one process has the potential to influence behaviors in seemingly unconnected processes, and a considerable proportion of trait variation in natural populations may be caused by the cumulative effects of many small effect-size genetic variants. The core processes that are discovered in Chapter 2 can be affected by many types of genetic changes. In Chapter 3, in collaboration with Angelika Amon lab, I followed a specific type of mutation, aneuploidy, and experimentally measured the effects of aneuploidy-associated stresses on three different yeast traits, namely galactose response, DTT response and heat shock response. The results showed that, aneuploidy can generally increase cell-to-cell variability in an isogenic population. In Chapter 4, I will present a few potentially interesting directions. Overall the results presented in this thesis improved our understanding about potential source of quantitative trait variation.