Genealogical evidence for positive selection in the nef gene of HIV-1

The pattern and process of evolution in the nef gene of HIV-1 was analyzed within and among patients. Using a maximum likelihood method that allows fo r variable intensity of selection pressure among codons, strong positive se lection was detected in a hemophiliac patient over 30 mo of infection. By r econstructing the process of allele substitution in this patient using pars imony, the synapomorphic amino acid changes separating each time point were found to have high probabilities of being under positive selection, with s elective coefficients of at least 3.6%. Positive selection was also detecte d among 39 nef sequences from HIV-1 subtype B. Tn contrast, multiple pairwi se comparisons of nonsynonymous and synonymous substitution rates provided no good evidence for positive selection and sliding window analyses failed to detect most positively selected sites. These findings demonstrate that p ositive selection is an important determinant of nef gene evolution and tha t genealogy-based methods outperform pairwise methods in the detection of a daptive evolution. Mapping the locations of positively selected sites may a lso be of use in identifying targets of the immune response and hence aid v accine design.