The evolution of mRNA splicing in mammals

Abstract

In this thesis, I describe investigations into the evolution of splicing in mammals. I first investigate a small class of alternative splicing events, tandem splice sites, and show how they are used to introduce and remove coding sequence in a species-specific manner. I then describe the generation and analysis of a large RNA-seq dataset from 9 matched tissues in 5 species, with the aim to investigate the evolution of splicing in mammals. I first investigate the evolution of exons that predate the most ancient divergence of species studied, finding that their splicing is frequently poorly conserved. For a subset of these exons, I identify unique regulatory properties and provide evidence linking alternative splicing to phosphorylation potential of proteins. I then consider sources of novel exons, in these species. I use these and other published data to identify one way in which splicing of novel exons impacts the biology of the cell. I also present evidence implicating genomic indels in exon creation and splicing variation.