Date of Award
Doctor of Philosophy (PhD)
Genomics & Computational Biology
Genome-wide regulation of gene expression involves a dynamic epigenetic structure which generates an organism's life-cycle. Although changes in gene expression during development have broad effects on many basic phenomena including cell growth, differentiation, morphogenesis, and disease progression, the evolutionary forces influencing gene expression dynamics and gene regulation remain largely unknown, due to the nature of gene expression as a polygenic, quantitative trait. Moreover, gene expression is regulated differentially over time, so evolutionary forces may be influenced by developmental context. To advance the understanding of evolution in the context of the life-cycle, the architecture of gene expression timing control and its influence on expression dynamics must be revealed. This dissertation presents two experimental investigations of the evolution of genes and related structural regions and time-dependent gene expression, using the budding yeasts Saccharomyces cerevisiae and Saccharomyces paradoxus and their mitotic cell-division cycle as model organism and life-cycle. Comparative methodologies were employed to analyze genome-wide patterns of genetic and phenotypic diversity within and between species. Analysis of several dozen yeast genomes reveals a dominant evolutionary mode of purifying selection. Despite limited genetic variability, differences in transcriptional regulation appear to contribute predominantly to interspecies divergence, and altered post-transcriptional regulation of ribosomal genes may have altered the timing of each species' transition from vegetative growth to reproduction, a classic life-history trait. In addition, natural variation in genome-wide gene expression was measured as a time-series through the mitotic cell-division cycle of 10 yeast lines, including one outgroup species. Despite levels of variation consistent with strong stabilizing selection, transcriptome coexpression dynamics have diverged significantly within and between species. A model involving timing pattern changes explains 61% of the between-genome variation in expression dynamics, suggesting that the major mode of transcriptome evolution involves changes in timing (heterochrony) rather than changes in levels (heterometry) of expression. Analysis of heterochrony patterns suggests that timing control is organized into distinct and dynamically-autonomous modules. Divergence in expression dynamics may be explained by pleiotropic changes in modular timing control. Genome-wide gene regulation may utilize a general architecture comprised of multiple discrete event timelines, whose superposition could produce combinatorial complexity in timing patterns.
Simola, Daniel F., "Evolution of Genome-wide Gene Regulation in the Budding Yeast Cell-Division Cycle" (2009). Publicly Accessible Penn Dissertations. 67.