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Evidence for widespread subfunctionalization of splice forms in vertebrate genomes
Gene duplication and alternative splicing are important sources of proteomic diversity. Despite research indicating that gene duplication and alternative splicing are negatively correlated, the evolutionary relationship between the two remains unclear. One manner in which alternative splicing and ge...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417111/ https://www.ncbi.nlm.nih.gov/pubmed/25792610 http://dx.doi.org/10.1101/gr.184473.114 |
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author | Lambert, Matthew J. Cochran, Wayne O. Wilde, Brandon M. Olsen, Kyle G. Cooper, Cynthia D. |
author_facet | Lambert, Matthew J. Cochran, Wayne O. Wilde, Brandon M. Olsen, Kyle G. Cooper, Cynthia D. |
author_sort | Lambert, Matthew J. |
collection | PubMed |
description | Gene duplication and alternative splicing are important sources of proteomic diversity. Despite research indicating that gene duplication and alternative splicing are negatively correlated, the evolutionary relationship between the two remains unclear. One manner in which alternative splicing and gene duplication may be related is through the process of subfunctionalization, in which an alternatively spliced gene upon duplication divides distinct splice isoforms among the newly generated daughter genes, in this way reducing the number of alternatively spliced transcripts duplicate genes produce. Previously, it has been shown that splice form subfunctionalization will result in duplicate pairs with divergent exon structure when distinct isoforms become fixed in each paralog. However, the effects of exon structure divergence between paralogs have never before been studied on a genome-wide scale. Here, using genomic data from human, mouse, and zebrafish, we demonstrate that gene duplication followed by exon structure divergence between paralogs results in a significant reduction in levels of alternative splicing. In addition, by comparing the exon structure of zebrafish duplicates to the co-orthologous human gene, we have demonstrated that a considerable fraction of exon divergent duplicates maintain the structural signature of splice form subfunctionalization. Furthermore, we find that paralogs with divergent exon structure demonstrate reduced breadth of expression in a variety of tissues when compared to paralogs with identical exon structures and singletons. Taken together, our results are consistent with subfunctionalization partitioning alternatively spliced isoforms among duplicate genes and as such highlight the relationship between gene duplication and alternative splicing. |
format | Online Article Text |
id | pubmed-4417111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44171112015-11-01 Evidence for widespread subfunctionalization of splice forms in vertebrate genomes Lambert, Matthew J. Cochran, Wayne O. Wilde, Brandon M. Olsen, Kyle G. Cooper, Cynthia D. Genome Res Research Gene duplication and alternative splicing are important sources of proteomic diversity. Despite research indicating that gene duplication and alternative splicing are negatively correlated, the evolutionary relationship between the two remains unclear. One manner in which alternative splicing and gene duplication may be related is through the process of subfunctionalization, in which an alternatively spliced gene upon duplication divides distinct splice isoforms among the newly generated daughter genes, in this way reducing the number of alternatively spliced transcripts duplicate genes produce. Previously, it has been shown that splice form subfunctionalization will result in duplicate pairs with divergent exon structure when distinct isoforms become fixed in each paralog. However, the effects of exon structure divergence between paralogs have never before been studied on a genome-wide scale. Here, using genomic data from human, mouse, and zebrafish, we demonstrate that gene duplication followed by exon structure divergence between paralogs results in a significant reduction in levels of alternative splicing. In addition, by comparing the exon structure of zebrafish duplicates to the co-orthologous human gene, we have demonstrated that a considerable fraction of exon divergent duplicates maintain the structural signature of splice form subfunctionalization. Furthermore, we find that paralogs with divergent exon structure demonstrate reduced breadth of expression in a variety of tissues when compared to paralogs with identical exon structures and singletons. Taken together, our results are consistent with subfunctionalization partitioning alternatively spliced isoforms among duplicate genes and as such highlight the relationship between gene duplication and alternative splicing. Cold Spring Harbor Laboratory Press 2015-05 /pmc/articles/PMC4417111/ /pubmed/25792610 http://dx.doi.org/10.1101/gr.184473.114 Text en © 2015 Lambert et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Lambert, Matthew J. Cochran, Wayne O. Wilde, Brandon M. Olsen, Kyle G. Cooper, Cynthia D. Evidence for widespread subfunctionalization of splice forms in vertebrate genomes |
title | Evidence for widespread subfunctionalization of splice forms in vertebrate genomes |
title_full | Evidence for widespread subfunctionalization of splice forms in vertebrate genomes |
title_fullStr | Evidence for widespread subfunctionalization of splice forms in vertebrate genomes |
title_full_unstemmed | Evidence for widespread subfunctionalization of splice forms in vertebrate genomes |
title_short | Evidence for widespread subfunctionalization of splice forms in vertebrate genomes |
title_sort | evidence for widespread subfunctionalization of splice forms in vertebrate genomes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417111/ https://www.ncbi.nlm.nih.gov/pubmed/25792610 http://dx.doi.org/10.1101/gr.184473.114 |
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