Functional Evolutionary Genomics: Yeast as a Model System.

Abstract

A long-standing and central question in evolutionary biology is the molecular genetic mechanisms of phenotypic evolution. However, this question is notoriously difficult because the relationships between genotypes and phenotypes are complex and often subtle. My study aims to use functional genomics approaches to understand how variations at the DNA level influence the functions and expressions of genes as well as the phenotype. Integrating functional genomics into evolutionary genetics is of significant importance, because this integration bridges the analyses of genotypes and phenotypes by the information of gene function and extends the understanding of the genotype-phenotype relationship to the genomic scale. In my studies, I used the budding yeast Saccharomyces cerevisiae as a model organism because of the availability of extensive functional genomic data and various genetic manipulation tools. Following the introductory chapter, I describe a study of the evolutionary rate of protein-protein interaction in Chapter 2. My results show that protein interaction is extremely conserved evolutionarily in the absence of gene duplication, and suggest a complex relationship between protein sequence evolution and protein function evolution. In Chapter 3, I studied genetic interactions in metabolic networks. We found that positive epistasis usually involves essential reactions, is highly abundant, and surprisingly, often occurs between reactions without overlapping functions. These results show that statistical epistasis does not necessarily indicate functional relations. In Chapter 4, I studied the relationship between tRNA concentrations and synonymous codon usage, and found that a balance between the synonymous codon fractions in the transcriptome and the cognate tRNA fractions optimizes the cellular translational efficiency. In Chapter 5, I aimed to identify genes that are beneficial in some environments but deleterious in other environments (i.e. antagonistic pleiotropy). We discovered pervasive antagonistic pleiotropy in yeast, studied the cause of its presence, and identified genetic mechanisms of its resolution in evolution. In sum, I capitalize on the recent progress in molecular genetics and functional genomics to study the molecular genetic basis of phenotypic variation in yeast. I expect the insights gained from this series of studies will shed light on the evolutionary process in other species, including multicellular eukaryotes such as humans.