This study is focused on mechanisms of molecular evolution of different epitope regions in HIV-1 genome, particularly, assessing the extent of nucleotide and amino acid sequence conservation and delineating selective forces acting on conformational and linear epitopes. The pattern of evolutionary changes influenced by selective pressures in the HIV-1 genome of B and Recombinant forms were assessed by 1) Estimating the extent of synonymous and nonsynonymous nucleotide substitutions and by 2) Estimating the numbers of radical and conservative amino acid changes.
The patterns of nucleotide and amino acid substitutions were estimated at conformational and linear epitopes and were contrasted among different types of epitopes to determine the pattern of selective pressure acting across different types of epitope regions. The results showed a pattern of strong purifying selection acting at the majority of epitope regions in all three major genes surveyed, Gag, Pol and Env. With respect to amino acid substitutions, while the conservative changes outnumbered radical in majority of the epitope regions (thus, indicating that purifying selection is a dominant selective force removing deleterious effects of drastic amino acid changes), some HIV-1 genomic regions showed a trend toward an increased number of radical amino acid changes.
Overall, this study showed that conformational epitopes are much more conserved than linear epitopes, and that although conformational epitope regions evolve predominantly through purifying selection, some sites within these regions may also be subject of positive selection.indicates that, similar to linear epitopes, conformational epitopes are also experiencing conflicting (and potentially episodic) selective pressures between positive selection that favors mutations to facilitate escape from the host immune system and purifying selection due to functional and structural constraints acting at the protein level.