The ratio of replacement to silent divergence and tests of neutrality

Comparisons of replacement to silent divergence have been used in a variety of studies aimed at detecting selection. Here, such comparisons are shown to be very sensitive to the pattern of rate variation in replacement sites. Saturation may play an important role even at surprisingly low levels of divergence if the substitution rate varies across replacement sites. For example, saturation in replacement sites may be of importance in the evolution of the HIV-I envelope gene. However, the pattern of saturation in replacement and silent sites may, in itself, provide valuable insight into the causes of DNA evolution. 210 DNA sequences from 15 different loci/systematic groups are analyzed, and evidence for positive selection is demonstrated in at least one of these data sets, through an analysis of the distribution of substitution rates along the sequence.