Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lambert, Matthew J., Cochran, Wayne O., Wilde, Brandon M., Olsen, Kyle G., Cooper, Cynthia D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
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
_version_ 1782369307131379712
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
work_keys_str_mv AT lambertmatthewj evidenceforwidespreadsubfunctionalizationofspliceformsinvertebrategenomes
AT cochranwayneo evidenceforwidespreadsubfunctionalizationofspliceformsinvertebrategenomes
AT wildebrandonm evidenceforwidespreadsubfunctionalizationofspliceformsinvertebrategenomes
AT olsenkyleg evidenceforwidespreadsubfunctionalizationofspliceformsinvertebrategenomes
AT coopercynthiad evidenceforwidespreadsubfunctionalizationofspliceformsinvertebrategenomes