The Evolution of Spliceosomal Introns

Indiana University, Bloomington IN

Investigators

Abstract

Many of the deepest unsolved mysteries in molecular genetics and genomics concern the mechanisms responsible for the differential proliferation of introns (intragenic non-coding spacers) in the protein-coding genes of various lineages of eukaryotes. Although introns impose numerous costs upon their host genomes, it has recently become clear that natural selection has exploited their presence in some genomes for various management aspects of messenger RNAs, including nuclear export and mRNA surveillance. However, the molecular source of introns and their rate of turnover remain virtually unknown. The general goals of this project are to develop an understanding of the molecular and population-genetic mechanisms that drive the dynamics of birth and loss of introns and to elucidate the phylogenetic distribution and history of the components of the spliceosome (the molecular machine involved in the cytoplasm), the exon-junction complex (the machinery involved in messenger RNA transport), and the nonsense-mediated decay pathway (a surveillance mechanism for removing defective messenger RNAs). These goals will be achieved by performing comprehensive bioinformatic surveys of the completely, or nearly completely, sequenced genomes of diverse eukaryotes. Although purely bioinformatic in scope, this project has the potential to answer many of the unresolved questions regarding the basic evolutionary biology of introns. In addition, the project will enhance the training of graduate students and a postdoctoral associate in bioinformatics and lead to the refinement of valuable whole-genome analysis tools.