Origin and Evolution of Novel Sequences by Gene Duplication.

Abstract

Gene duplication is a key source of genetic innovation. The recent availability of whole-genome sequences from a number of closely-related species makes it possible to directly investigate how gene duplication influences genomic evolution over time. This thesis utilizes techniques from comparative genomics to elucidate the origin and evolution of novel sequences by gene duplication. First, I explored the evolutionary dynamics of nested genes, which are genes embedded in the introns of other genes. I found that nested genes were primarily gained during metazoan evolution, often via the duplication and insertion of un-nested genes found in other genomic regions. Strikingly, the accumulation of nested genes is driven by a neutral process that is likely due to the presence of many long unsaturated introns in animal genomes. Next, I investigated the origin of long transcripts, or “clusters”, containing Piwi-interacting RNAs (piRNAs), which are small RNAs believed to play a role in transposon silencing. By comparing orthologous regions of rat, mouse, and human genomes, I discovered that 41% of clusters are unique to a particular rodent genome, having arisen via the duplication and insertion of other clusters located on the same chromosomes. Upon further examination, I elucidated the insertion mechanisms of most recently-acquired clusters as ectopic recombination of their flanking repetitive elements. Because the rate of cluster expansion is higher than that of any known gene family, it is likely that this process is driven by positive selection, perhaps caused by the need to silence the ever-expanding repertoire of mammalian transposons. Finally, I studied insertions and deletions produced by nonallelic gene conversion, which is the unidirectional transfer of genetic information between duplicate genes. I uncovered a strong deletion bias in nonallelic gene conversion in textit{Drosophila} and primates. Moreover in both lineages, the rate of nonallelic gene conversion is much faster than that of ordinary mutation, leading to the cooperative shrinkage and eventual disappearance of selectively neutral duplicate genes. Together, this dissertation research encompasses the evolutionary processes both leading to and following gene duplication, shedding light on one of the most important forces in genomic evolution.