Positive and negative selection in the DAZ gene family

Because a microdeletion containing the DAZ gene is the most frequently obse rved deletion in infertile men, the DAZ gene was considered a strong candid ate for the azoospermia factor. A recent evolutionary analysis, however sug gested that DAZ was free from functional constraints and consequently playe d little or no role in human spermatogenesis. The major evidence for this s urprising conclusion is that the nonsynonymous substitution rate is similar to the synonymous rate and to the rate in introns. In this study, we reexa mined the evolution of the DAZ gene family by using maximum-likelihood meth ods, which accommodate variable selective pressures among sites or among br anches. The results suggest that DAZ is not free from functional constraint s. Most amino acids in DAZ are under strong selective constraint, while a f ew sites are under diversifying selection with nonsynonymous/ synonymous ra te ratios (d(N)/d(S)) well above 1. As a result, the average d(N)/d(S) rati o over sites is not a sensible measure of selective pressure on the protein . Lineage-specific analysis indicated that human members of this gene famil y were evolving by positive Darwinian selection, although the evidence was not strong.