The evolution of mRNA splicing in mammals

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2014

Author dc:creator

• Merkin, Jason Jay

Advisor dc:contributor.advisor

• Christopher B. Burge.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/89945

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/89945