Title: Evolutionary molecular clocks
Description: This work focuses on rates of evolution, exploring sequence change, gene structure evolution and gene expression divergence. Although this is a popular topic in the evolutionary genetics literature, most studies of evolutionary rates do not employ null models and instead rely on comparisons between genes. Here I seek to provide a framework for the study of evolutionary rates. Simple models of molecular evolution predict that both sequences and quantitative traits should evolve in accordance with a "molecular evolutionary clock," wherein divergence is proportional to time. Through study of deviations from the null model of a molecular clock, insight can be gained into the forces shaping evolution of genotype and phenotype. With regard to sequence evolution, the molecular clock hypothesis further predicts that the accumulation of sequence change should follow a Poisson process in which nucleotide or amino acid substitutions occur as rare independent events. Generally, substitution patterns that show greater variance than the Poisson expectation are said to be "overdispersed." Comparing the genomes of closely related species of yeast, Drosophila and mammals, I find that sequence change is clock-like, but overdispersed. Additionally, I find that the extent of overdispersion varies significantly between yeast, Drosophila and mammals, showing a strong negative correlation with the effective population sizes of these organisms. These results are consistent with theoretical predictions of evolution over nearly neutral networks.

On the other hand, I find that gene expression divergence across seven species of Drosophila does not follow a molecular clock, instead saturating quickly across the Drosophila phylogeny. This is consistent with the action of stabilizing selection holding expression divergence in check. These results, taken together, suggest that sequences and their biological outcomes evolve in fundamentally different fashions, owing to the complex mapping between genotype and phenotype.