Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues
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 biolo...
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/84699 |
| _version_ | 1826212363433410560 |
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| author | Merkin, Jason Jay Russell, Caitlin Chen, Ping Burge, Christopher B |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Merkin, Jason Jay Russell, Caitlin Chen, Ping Burge, Christopher B |
| author_sort | Merkin, Jason Jay |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:20:31Z |
| format | Article |
| id | mit-1721.1/84699 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:20:31Z |
| publishDate | 2014 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/846992022-09-29T14:19:25Z Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues Merkin, Jason Jay Russell, Caitlin Chen, Ping Burge, Christopher B Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Merkin, Jason Jay Russell, Caitlin Chen, Ping Burge, Christopher B. 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. Broad Institute of MIT and Harvard (SPARC grant) National Institutes of Health (U.S.) (NIH training grant) Academy of Finland (Center of Excellence in Cancer Genetics Research) Sigrid Jusélius Foundation Global FICS (Foundation for International Cardiovascular Services) National Institutes of Health (U.S.) (grant OD011092) National Science Foundation (U.S.) (grant 0821391) 2014-02-07T19:24:35Z 2014-02-07T19:24:35Z 2012-12 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/84699 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. en_US http://dx.doi.org/10.1126/science.1228186 Science 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. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Merkin, Jason Jay Russell, Caitlin Chen, Ping Burge, Christopher B Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues |
| title | Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues |
| title_full | Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues |
| title_fullStr | Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues |
| title_full_unstemmed | Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues |
| title_short | Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues |
| title_sort | evolutionary dynamics of gene and isoform regulation in mammalian tissues |
| url | http://hdl.handle.net/1721.1/84699 |
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