Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues
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Burge_Evolutionary dynamics.pdf
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3.53 MB
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Author(s)
Merkin, Jason Jay
Russell, Caitlin
Chen, Ping
Burge, Christopher B
Date Issued
December 2012
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Merkin, J., C. Russell, P. Chen, and C. B. Burge. “Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues.” Science 338, no. 6114 (December 20, 2012): 1593-1599.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/science.1228186
