The KA/KS ratio test for assessing the protein-coding potential of genomic regions:: An empirical and simulation study

Comparative genomics is a simple, powerful way to increase the accuracy of gene prediction. In this study, we show the utility of a simple test for the identification of protein-coding exons using human/mouse sequence comparisons. The test takes advantage of the fact that in the vast majority of coding regions, synonymous substitutions (K-S) Occur much more frequently than nonsynonymous ones (K-A) and uses the K-A/K-S ratio as the criterion. We show the following: (1) most of the human and mouse exons are sufficiently long and have a suitable degree of sequence divergence for the test to perform reliably; (2) the test is suited for the identification of long exons and single exon genes, which are difficult to predict by Current methods; (3) the test has a false-negative rate, lower than most Of Current gene prediction methods and a false-positive rate lower than all Current methods; (4) the test has been automated and call be used in combination with other existing gene-prediction methods.