LIKELIHOOD MODELS FOR DETECTING POSITIVELY SELECTED AMINO-ACID SITES AND APPLICATIONS TO THE HIV-1 ENVELOPE GENE

Several codon-based models for the evolution of protein-coding DNA seq uences are developed that account for varying selection intensity amon g amino acid sites. The ''neutral model'' assumes two categories of si tes at which amino acid replacements are either neutral or deleterious . The ''positive-selection model'' assumes an additional category of p ositively selected sites at which nonsynonymous substitutions occur at a higher rate than synonymous ones. This model is also used to identi fy target sites for positive selection. The models are applied to a da ta set of the V3 region of the HIV-1 envelope gene, sequenced at diffe rent years after the infection of one patient. The results provide str ong-support for variable selection intensity among amino acid sites Th e neutral model is rejected in favor of the positive-selection model, indicating the operation of positive selection in the region. Positive ly selected sites are found in both the V3 region and the flanking reg ions.