RGD Reference Report - Evolutionary dynamics of gene and isoform regulation in Mammalian tissues. - Rat Genome Database

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Evolutionary dynamics of gene and isoform regulation in Mammalian tissues.

Authors: Merkin, Jason  Russell, Caitlin  Chen, Ping  Burge, Christopher B 
Citation: Merkin J, etal., Science. 2012 Dec 21;338(6114):1593-9. doi: 10.1126/science.1228186.
RGD ID: 14995303
Pubmed: PMID:23258891   (View Abstract at PubMed)
PMCID: PMC3568499   (View Article at PubMed Central)
DOI: DOI:10.1126/science.1228186   (Journal Full-text)

Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR, and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling.

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