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Genome Res. 2015 May;25(5):624-32. doi: 10.1101/gr.184473.114. Epub 2015 Mar 19.

Evidence for widespread subfunctionalization of splice forms in vertebrate genomes.

Author information

  • 1School of Biological Sciences, Washington State University, Pullman, Washington 99164, USA;
  • 2School of Engineering and Computer Science, Washington State University Vancouver, Vancouver, Washington 98686, USA;
  • 3College of Arts and Sciences, Washington State University Vancouver, Vancouver, Washington 98686, USA;
  • 4School of Biological Sciences, Washington State University, Pullman, Washington 99164, USA; School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USA.

Abstract

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.

PMID:
25792610
PMCID:
PMC4417111
DOI:
10.1101/gr.184473.114
[PubMed - indexed for MEDLINE]
Free PMC Article
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