Grant: Discovery Grants Program - Individual

The main focus of our research over the past five years was on "genome dynamics", i.e., the patterns of evolutionary change in genome structure and composition. More specifically, we surveyed the patterns of variation in the nucleotide contents of many completely sequenced genomes, and we then correlated these variations in genome composition with variations in synonymous codon usage and the amino acid composition of the corresponding proteomes. We also performed a series of bioinformatics analyses in order to infer the respective evolutionary effects of natural selection, mutational bias and genetic drift. Our goal was to answer, at least in part, the following question: are the variations in nucleotide content, both within and between genomes, mainly due to the effects of natural selection acting at the protein level, or are they instead due primarily to the effects of fluctuating mutational biases at the nucleotide level. Our published results, along with our current investigations indicate that the data can best be explained by a combination of both nucleotide-level mutational biases and proteome-level natural selection. Our proposed research will continue to dissect these evolutionary forces, while adding a new dimension - the effect of variations in genetic recombination rates. This work is important because it provides a framework for evaluating the many recent reports of selection in the human genome, and in other genomes. These reports, which are generally based on comparative sequence data, often ignore many of the factors that can influence genome evolution in the absence of positive Darwinian selection (for a recent review, see Nielsen et al., 2007).