Isoform Identification

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Science  04 May 2012:
Vol. 336, Issue 6081, pp. 520-521
DOI: 10.1126/science.336.6081.520-d

The differential reconnection of transcribed exons, termed alternative splicing, has the potential to result in one gene encoding multiple protein isoforms. The degree to which alternatively spliced transcripts are translated into functional proteins, however, is not well understood. Ezkurdia et al. used data across multiple mass spectrometry experiments to investigate the degree to which genes with alternative transcripts gave rise to protein isoforms. Comparison of the predicted proteins from the gene and genetic variant database of ENCODE (GENCODE) to the Swiss-Prot database allowed for the identification of 150 human genes that encoded at least one protein isoform and 13 with three or more, with the caveat that identification was biased toward those most likely to be detected. Heterogeneous nuclear ribonucleoproteins, which are involved in the regulation of alternative splicing, showed enrichment in alternative isoforms. Furthermore, the majority of differences detected among all predicted isoforms differed in sequence by the insertion/deletion of a single amino acid. Investigations into the Drosophila and mouse proteomes revealed similar patterns. Together, these results suggest that alternative splicing is under selective constraint.

Mol. Biol. Evol. 29, 10.1093/molbev/mss100 (2012).

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