A simple covarion-based approach to analyse nucleotide substitution rates

Using the ratio of nonsynonymous to synonymous nucleotide substitution rates (Ka/Ks) is a common approach for detecting positive selection. However, calculation of this ratio over a whole gene combines amino acid sites that may be under positive selection with those that are highly conserved. We introduce a new covarion-based method to sample only the sites potentially under selective pressure. Using ancestral sequence reconstruction over a phylogenetic tree coupled with calculation of Ka/Ks ratios, positive selection is better detected by this simple covarion-based approach than it is using a whole gene analysis or a windowing analysis. This is demonstrated on a synthetic dataset and is tested on primate leptin, which indicates a previously undetected round of positive selection in the branch leading to Gorilla gorilla.