Bielawski J P, Yang Z
Department of Biology, Galton Laboratory, University College London, England.
Mol Biol Evol. 2001 Apr;18(4):523-9. doi: 10.1093/oxfordjournals.molbev.a003831.
Because a microdeletion containing the DAZ gene is the most frequently observed deletion in infertile men, the DAZ gene was considered a strong candidate for the azoospermia factor. A recent evolutionary analysis, however, suggested that DAZ was free from functional constraints and consequently played little or no role in human spermatogenesis. The major evidence for this surprising conclusion is that the nonsynonymous substitution rate is similar to the synonymous rate and to the rate in introns. In this study, we reexamined the evolution of the DAZ gene family by using maximum-likelihood methods, which accommodate variable selective pressures among sites or among branches. The results suggest that DAZ is not free from functional constraints. Most amino acids in DAZ are under strong selective constraint, while a few sites are under diversifying selection with nonsynonymous/ synonymous rate ratios (d(N)/d(S)) well above 1. As a result, the average d(N)/d(S) ratio over sites is not a sensible measure of selective pressure on the protein. Lineage-specific analysis indicated that human members of this gene family were evolving by positive Darwinian selection, although the evidence was not strong.
由于包含DAZ基因的微缺失是在不育男性中最常观察到的缺失，因此DAZ基因被认为是无精子症因子的有力候选者。然而，最近的一项进化分析表明，DAZ不受功能限制，因此在人类精子发生中几乎没有或根本没有作用。这一惊人结论的主要证据是，非同义替换率与同义替换率以及内含子中的替换率相似。在本研究中，我们使用最大似然法重新审视了DAZ基因家族的进化，该方法考虑了位点间或分支间的可变选择压力。结果表明，DAZ并非不受功能限制。DAZ中的大多数氨基酸受到强烈的选择限制，而少数位点则受到多样化选择，非同义/同义率比（d(N)/d(S)）远高于1。因此，位点上的平均d(N)/d(S)比不是对蛋白质选择压力的合理衡量。谱系特异性分析表明，该基因家族的人类成员是通过正达尔文选择进化而来的，尽管证据并不充分。
