Simultaneous Positive and Purifying Selection on Overlapping Reading Frames of thetatandvprGenes of Simian Immunodeficiency Virus

Abstract
Tat-specific cytotoxic T cells have previously been shown to exert positive Darwinian selection favoring amino acid replacements of an epitope of simian immunodeficiency virus (SIV). The region of thetatgene encoding this epitope falls within a region of overlap between thetatandvprreading frames, and nonsynonymous nucleotide substitutions in thetatreading frame were found to occur disproportionately in such a way as to cause synonymous changes in thevprreading frame. Comparison of published complete SIV genomes showed Tat to be the least conserved at the amino acid level of nine proteins encoded by the virus, while Vpr was one of the most conserved. Numerous parallel amino acid changes occurred within the Tat epitope independently in different monkeys, and purifying selection on thevprreading frame, by limiting acceptable nonsynonymous substitutions in thetatreading frame, evidently has enhanced the probability of parallel evolution.