Biological impact of mutually exclusive exon switching

Alternative splicing can expand the diversity of proteomes. Homologous mutually exclusive exons (MXEs) originate from the same ancestral exon and result in polypeptides with similar structural properties but altered sequence. Why would some genes switch homologous exons and what are their biological impact? Here, we analyse the extent of sequence, structural and functional variability in MXEs and report the first large scale, structure-based analysis of the biological impact of MXE events from different genomes. MXE-specific residues tend to map to single domains, are highly enriched in surface exposed residues and cluster at or near protein functional sites. Thus, MXE events are likely to maintain the protein fold, but alter specificity and selectivity of protein function. This comprehensive resource of MXE events and their annotations is available at: http://gene3d.biochem.ucl.ac.uk/mxemod/. These findings highlight how small, but significant changes at critical positions on a protein surface are exploited in evolution to alter function.

Origin and evolution of a new exon of 14-3-3ξ in bees and phylogenetic analysis

Mutually exclusive splicing, one type of alternative splicing, involves selection of alternatively spliced exons arranged in tandem and creates protein products with substitution of one segment of the amino acid sequence for another. Previous studies revealed that exon 5 of 14-3-3ξ from Apis mellifera (western honeybee) had three mutually exclusive exons, while orthologous exon of Nasonia vitripennis (parasitic wasp) had only two, suggesting that cases of exon gain or loss might have happened during the evolution of hymenopteran species. In the current study, we annotated and analyzed the 14-3-3ξ genes from 20 hymenopteran species successfully, and the results of phylogenetic analysis revealed the presence of a new mutually exclusive exon in corbiculate bees. In addition, we found that duplication via staggered homologous recombination was responsible for the origin of the new exon.