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Bioinformatics Advance Access published online on August 9, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti613
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received July 5, 2005
Revised August 3, 2005
Accepted August 3, 2005

Discovery note

Assessing the application of Ka/Ks ratio test to alternatively spliced exons

Yi Xing 1 and Christopher Lee 1*

1 Molecular Biology Institute, Center for Genomics and Proteomics, Dept. of Chemistry & Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1570

* To whom correspondence should be addressed.
Christopher Lee, E-mail: leec{at}mbi.ucla.edu


  Abstract

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.


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