Tandem exon duplication tends to propagate rather than to create de novo alternative splicing

Tandem gene duplication is one of the most prevalent ways of generating genes with new function. Similarly, tandem exon duplication is an important source of new exons. Tandem exon duplication is often associated with alternative splicing to reduce the possible deleterious impacts on transcript/protein structure. However, how alternative splicing is established on two new exons from duplication remains controversial. By analyzing the duplication of human-mouse conserved exons, we illustrated that newly duplicated exons tend to preserve the splicing status of their parent exon. That is, the exons duplicated from an alternative exon are usually alternatively spliced, while those from constitutive parents are more likely to be constitutively spliced. Newly generated, constitutively spliced exons showed a higher percentage of frame preservation and protein domain preference, indicating some evolutionary scenarios other than alternative splicing operates for the relief of negative selection pressure. These results suggest that alternative splicing is usually established before the tandem duplication. The duplication therefore propagates, rather than creates de novo, alternative splicing.