Detecting selection in the HIV-1 genome using the dn/ds ratio.

Rasmus Nielsen, Ziheng Yang, Nick Goldman and Anne-Mette Krabbe Pedersen.

Methods based on estimating the nonsynonymous/synonymous rate ratio provide a powerful and direct method for testing hypotheses regarding selection at the molecular level. Newly developed codon based likelihood methods can be applied to test hypotheses regarding molecular evolution. By allowing the rate of nonsynonymous substitution to vary along a sequence, it is possible to detect positive selection, even when the ratio of nonsynonymous to synonymous substitutions on average is much less than one. The new likelihood methods are applied to the HIV-1 env, vif and pol genes. Previous analyses of the vif and the pol gene using heuristic methods did not reveal evidence for positive selection. However, the new likelihood ratio test reveal strongly significant evidence for positive diversifying selection in the vif and pol genes in addition to the env gene. Subsequent to the detection of positive selection, an empirical Bayes method is used to identify which nucleotide sites are being targeted by selection.

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