Origins and Impacts of New Mammalian Exons

Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most ne...

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Main Authors: Merkin, Jason Jay, Chen, Ping, Alexis, Maria Sarah, Hautaniemi, Sampsa, Burge, Christopher B
Other Authors: Massachusetts Institute of Technology. Computational and Systems Biology Program
Format: Article
Language:en_US
Published: Elsevier 2015
Online Access:http://hdl.handle.net/1721.1/96260
https://orcid.org/0000-0003-4801-1369
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author Merkin, Jason Jay
Chen, Ping
Alexis, Maria Sarah
Hautaniemi, Sampsa
Burge, Christopher B
author2 Massachusetts Institute of Technology. Computational and Systems Biology Program
author_facet Massachusetts Institute of Technology. Computational and Systems Biology Program
Merkin, Jason Jay
Chen, Ping
Alexis, Maria Sarah
Hautaniemi, Sampsa
Burge, Christopher B
author_sort Merkin, Jason Jay
collection MIT
description Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most new exons derived from unique rather than repetitive intronic sequence. Unlike exons conserved across mammals, species-specific internal exons were mostly located in 5′ UTRs and alternatively spliced. They were associated with upstream intronic deletions, increased nucleosome occupancy, and RNA polymerase II pausing. Genes containing new internal exons had increased gene expression, but only in tissues in which the exon was included. Increased expression correlated with the level of exon inclusion, promoter proximity, and signatures of cotranscriptional splicing. Altogether, these findings suggest that increased splicing at the 5′ ends of genes enhances expression and that changes in 5′ end splicing alter gene expression between tissues and between species.
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spelling mit-1721.1/962602022-10-01T04:36:12Z Origins and Impacts of New Mammalian Exons Merkin, Jason Jay Chen, Ping Alexis, Maria Sarah Hautaniemi, Sampsa Burge, Christopher B Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Merkin, Jason Jay Alexis, Maria Sarah Burge, Christopher B. Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most new exons derived from unique rather than repetitive intronic sequence. Unlike exons conserved across mammals, species-specific internal exons were mostly located in 5′ UTRs and alternatively spliced. They were associated with upstream intronic deletions, increased nucleosome occupancy, and RNA polymerase II pausing. Genes containing new internal exons had increased gene expression, but only in tissues in which the exon was included. Increased expression correlated with the level of exon inclusion, promoter proximity, and signatures of cotranscriptional splicing. Altogether, these findings suggest that increased splicing at the 5′ ends of genes enhances expression and that changes in 5′ end splicing alter gene expression between tissues and between species. American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship National Science Foundation (U.S.) (Grant 0821391) National Institutes of Health (U.S.) (Grant 5-R01-HG002439) 2015-03-30T19:07:42Z 2015-03-30T19:07:42Z 2015-03 2015-01 Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/96260 Merkin, Jason J. et al. “Origins and Impacts of New Mammalian Exons.” Cell Reports (2015): n. pag. https://orcid.org/0000-0003-4801-1369 en_US http://dx.doi.org/10.1016/j.celrep.2015.02.058 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License http://creativecommons.org/licenses/by-nc-nd/3.0/ application/pdf Elsevier Elsevier Open Access
spellingShingle Merkin, Jason Jay
Chen, Ping
Alexis, Maria Sarah
Hautaniemi, Sampsa
Burge, Christopher B
Origins and Impacts of New Mammalian Exons
title Origins and Impacts of New Mammalian Exons
title_full Origins and Impacts of New Mammalian Exons
title_fullStr Origins and Impacts of New Mammalian Exons
title_full_unstemmed Origins and Impacts of New Mammalian Exons
title_short Origins and Impacts of New Mammalian Exons
title_sort origins and impacts of new mammalian exons
url http://hdl.handle.net/1721.1/96260
https://orcid.org/0000-0003-4801-1369
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