RNA Bioinformatics

Xing and Lee 2005, Bioinformatics

Summary: Recently, the Ka/Ks ratio test, which assesses the protein-coding potentials of genomic regions based on their nonsynonymous to synonymous divergence rates, has been proposed and successfully used in genome annotations of eukaryotes. In this manuscript we systematically performed the Ka/Ks ratio test on 925 transcript-confirmed alternatively spliced exons in the human genome. We found that 22.3% of evolutionarily conserved alternatively spliced exons cannot pass the Ka/Ks ratio test, compared to 9.8% for constitutive exons. The false negative rate was the highest (85.7%) for exons with low frequencies of transcript inclusion. Analyses of alternatively spliced exons supported by full-length mRNA sequences yielded similar results, and nearly half of exons involved in ancestral alternative splicing events couldn’t pass this test. Our analysis suggests a future direction to incorporate comparative genomics-based alternative splicing predictions with the Ka/Ks ratio test in higher eukaryotes with extensive RNA alternative splicing.

Contact: Christopher Lee (leec@mbi.ucla.edu)

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By the way, Chris Burge group's UNCOVER paper reported a similar finding on a set of ancestral alternative exons. See their supplemental material.