title: Revisit on the evolutionary relationship between alternative splicing and gene duplication.
abstract: Gene duplications and alternative splicing (AS) isoforms are two widespread types of genetic variations that can facilitate diversification of protein function. A number of studies claimed that after gene duplication, two AS isoforms with differential functions can be 'fixed', respectively, in each of the duplicate copies. This simple 'functional-sharing' hypothesis was recently challenged by Roux and Robinson-Rechavi (2011). Instead, they proposed a more sophisticated hypothesis, invoking that less alternative splicing genes tend to be duplicated more frequently, and single-copy genes are younger than duplicate genes, or the 'duplicability-age' hypothesis for short. In this letter, we show that all these genome-wide analyses of AS isoforms actually did not provide clear-cut evidence to nullify the basic idea of functional-sharing hypothesis. After updating our understanding of genome-wide alternative splicing, duplicability and CNV (copy number variation), we argue that the foundation of the duplicability-age hypothesis remains to be justified carefully. Finally, we suggest that a better approach to resolving this controversy is the correspondence analysis of indels (insertions and deletions) between duplicate genes to the genomic exon-intron structure, which can be used to experimentally test the effect of functional-sharing hypothesis.
authors.affiliation: MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Zhixi
authors.initials: Z
authors.lastname: Su
authors.forename: Xun
authors.initials: X
authors.lastname: Gu
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D020440:Gene Duplication; D020131:Genes, Duplicate; D055106:Genome-Wide Association Study; D006801:Humans; D007438:Introns / Q000235:genetics; D008957:Models, Genetic; D010802:Phylogeny; D011506:Proteins / Q000235:genetics*; D057386:Search Engine
chemical_list: D011506:Proteins