title: Assessing the application of Ka/Ks ratio test to alternatively spliced exons.
abstract: Recently, the Ka/Ks ratio test, which assesses the protein-coding potentials of genomic regions based on their non-synonymous to synonymous divergence rates, has been proposed and successfully used in genome annotations of eukaryotes. We systematically performed the Ka/Ks ratio test on 925 transcript-confirmed alternatively spliced exons in the human genome, which we describe in this manuscript. We found that 22.3% of evolutionarily conserved alternatively spliced exons cannot pass the Ka/Ks ratio test, compared with 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 could not 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.
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, Center for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095-1570, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
authors.forename: Christopher
authors.initials: C
authors.lastname: Lee
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D005091:Exons / Q000235:genetics*; D006801:Humans; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*