Molecular evolution meets the genomics revolution: Genome-scale studies of gene duplication, X-chromosome evolution, and developmental constraint.

摘要

Recent technological advances have generated an effusion of genome level data including complete genome DNA sequences, transcriptional information, and functional protein annotations. For the first time, it is becoming possible to address fundamental questions in molecular evolution from a genome-wide perspective. This type of approach involves developing tenable questions, which can be answered using available resources, and employing data mining skills, computational and statistical expertise, and knowledge about molecular evolutionary and population genetic theory to address them. This dissertation includes six such genome scale studies in the field of molecular evolution, divided into three chapters with two manuscripts each. The first chapter addresses how gene duplication contributes to genic diversity over evolutionary time. This work primarily addresses whether some types of genes are more likely to generate persistent duplicate genes than others. The included studies reveal that duplicate genes are a biased set and thus have important implications for how future genome scale studies of duplication are carried out. The second chapter explores the molecular evolution of the X chromosome. In the first section we compare patterns of codon bias on the X chromosome and the autosomes in three taxa to study how population genetic parameters affect molecular evolution. The second section discusses comparative genomic and maximum likelihood approaches, to understand inter-chromosomal gene movement between the X chromosome and the autosomes. In the third chapter we study the tempo of molecular divergence for genes expressed during different developmental stages. The first section explores how purifying selection and positive selection work to modulate non-synonymous rates of divergence for stage specific proteins. The second manuscript discusses patterns of upstream regulatory region divergence between three pairs of metazoan organisms; we discover that developmental genes possess among the most highly conserved upstream regulatory regions in the genome.