Alternative splicing (AS) is a common post-transcriptional process in eukaryotic
organisms, by which multiple distinct functional transcripts are produced from a single gene. Because of its potential role in expanding transcript diversity, interest in alternative splicing has been increasing over the last decade, ever since the release of the human genome draft showed it contained little more than the number of genes of a worm.
Although recent studies have shown that 94% human multi-exon genes undergo AS while aberrant AS may cause disease or cancer, evolution of AS in eukaryotic genomes remains largely unexplored mainly due to the lack of comparable AS estimates. In this thesis I built a Eukaryote Comprehensive & Comparable Alternative Splicing Events Database (ECCASED) based on the analyses of over 30 million Expressed Sequence Tag (ESTs) for 114 eukaryotic genomes, including protists (22), plants (20), fungi (23), metazoan (non-vertebrates, 29) and vertebrates (20). Using this database, I addressed two main questions: 1) How does alternative splicing relate to gene duplication (GD) as an
alternative mechanism to increase transcript diversity? and 2) What is the contribution of alternative splicing to eukaryote transcript diversity? I found that the previous “interchangeable model” of AS and gene duplication is a by-product of an existing relation between gene expression breadth, AS and gene family size. I also show that alternative splicing has played a key role in the expansion of transcript diversity and that this expansion is the best predictor reported to date of organisms complexity assayed as number of cell types. In addition, by comparing alternative splicing patterns in cancer and normal transcript libraries I found that cancer derived transcript libraries have increased levels of “noisy splicing”.
|Date of Award||23 Mar 2012|
|Supervisor||Araxi Urrutia (Supervisor) & Laurence Hurst (Supervisor)|
- alternative splicing
- comparative genomics