Investigating the Molecular Mechanisms of Evolutionary Novelty

Abstract

Evolution is the descent with modification from common ancestors. Forms and functions diversify as a result of changes in genomic sequence that result in changing molecular functions performed by biological molecules such as proteins, RNA, or DNA. Not all genetic changes, however, result in a change in molecular function; highly distinct gene sequences may nonetheless produce similar functions. At the same time, there are some genetic changes that have a significant effect on molecular function and sometimes highly similar gene sequences may nonetheless produce distinct functional molecules. In order to identify and understand the subsets of genetic changes that were responsible for novel functions, we must apply the tools of molecular biology within an evolutionary framework in order to specifically characterize the functional differentiation of diversified genotypes and further to understand the molecular mechanisms that mediated their functional effects. This dissertation has sought to contribute to this work in three related ways: first, by analyzing the dominant approach used in molecular evolutionary research and outlining a program of research that would best yield insight into the mechanisms of evolutionary change; second, by examining the genetic, biochemical, and biophysical mechanisms that gave rise to a novel DNA-binding function in the steroid receptor transcription factors; and third, by functionally characterizing the sequence space that separates the ancestral and derived DNA-binding function across that evolutionary transition. This body of work has sought to contribute to our general understanding of the principles that underlie the evolutionary process by characterizing the molecular mechanisms that were responsible for some of the interesting, diverse functions that evolution has produced. In doing so, it points towards some important potential general principles that guide evolutionary processes.

This dissertation includes published and unpublished co-authored material.