Evidence for heterogeneous selective pressures in the evolution of the env gene in different human immunodeficiency virus type 1 subtypes.

Recent studies have demonstrated the emergence of human immunodeficiency virus type 1 (HIV-1) subtypes with various levels of fitness. Using heterogeneous maximum-likelihood models of adaptive evolution implemented in the PAML software package, with env sequences representing each HIV-1 group M subtype, we examined the various intersubtype selective pressures operating across the env gene. We found heterogeneity of evolutionary mechanisms between the different subtypes with a category of amino acid sites observed that had undergone positive selection for subtypes C, F1, and G, while these sites had undergone purifying selection in all other subtypes. Also, amino acid sites within subtypes A and K that had undergone purifying selection were observed, while these sites had undergone positive selection in all other subtypes. The presence of such sites indicates heterogeneity of selective pressures within HIV-1 group M subtype evolution that may account for the various levels of fitness of the subtypes.