Biological impact of mutually exclusive exon switching.

Su Datt Lam, M Madan Babu, Jonathan Lees, Christine A Orengo

PLoS computational biology 2021 Mar

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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.

Citation

Su Datt Lam, M Madan Babu, Jonathan Lees, Christine A Orengo. Biological impact of mutually exclusive exon switching. PLoS computational biology. 2021 Mar;17(3):e1008708