Gene duplication followed by exon structure divergence substitutes for alternative splicing in zebrafish

- Gene duplication and alternative splicing both increase proteomic diversity.
- We compare levels of alternative splicing in duplicate and non-duplicate genes.
- Paralogs not diverging in exon structure do not undergo less alternative splicing.
- Paralogs that undergo exon structure divergence display less alternative splicing.
- Splice form subfunctionalization explains this reduction in alternative splicing.

In this study we report novel findings regarding the evolutionary relationship between gene duplication and alternative splicing, two processes that increase proteomic diversity. By studying teleost fish, we find that gene duplication followed by exon structure divergence between paralogs, but not gene duplication alone, leads to a significant reduction in alternative splicing, as measured by both the proportion of genes that undergo alternative splicing as well as mean number of transcripts per gene. Additionally, we show that this effect is independent of gene family size and gene function. Furthermore, we provide evidence that the reduction in alternative splicing may be due to the partitioning of ancestral splice forms among the duplicate genes - a form of subfunctionalization. Taken together these results indicate that exon structure evolution subsequent to gene duplication may be a common substitute for alternative splicing.