Gasper Joe, Swanson Willie J
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Am J Hum Genet. 2006 Nov;79(5):820-30. doi: 10.1086/508473. Epub 2006 Sep 15.
A hallmark of positive selection (adaptive evolution) in protein-coding regions is a d(N)/d(S) ratio >1, where d(N) is the number of nonsynonymous substitutions/nonsynonymous sites and d(S) is the number of synonymous substitutions/synonymous sites. Zonadhesin is a male reproductive protein localized on the sperm head, comprising many domains known to be involved in cell-cell interaction or cell adhesion. Previous studies have shown that VWD domains (homologous to the D domains of the von Willebrand factor) are involved directly in binding to the female zona pellucida (ZP) in a species-specific manner. In this study, we sequenced 47 coding exons in 12 primate species and, by using maximum-likelihood methods to determine sites under positive selection, we show that VWD2, membrane/A5 antigen mu receptor, and mucin-like domains in zonadhesin are rapidly evolving and, thus, may be involved in binding to the ZP in a species-specific manner in primates. In addition, polymorphism data from 48 human individuals revealed significant polymorphism-to-divergence heterogeneity and a significant departure from equilibrium-neutral expectations in the frequency spectrum, suggesting balancing selection and positive selection occurring in zonadhesin (ZAN) within human populations. Finally, we observe adaptive evolution in haplotypes segregating for a frameshift mutation that was previously thought to indicate that ZAN was a potential pseudogene.
蛋白质编码区域正向选择（适应性进化）的一个标志是d(N)/d(S)比率大于1，其中d(N)是非同义替换数/非同义位点，d(S)是同义替换数/同义位点。透明带粘附素是一种位于精子头部的雄性生殖蛋白，由许多已知参与细胞间相互作用或细胞粘附的结构域组成。先前的研究表明，VWD结构域（与血管性血友病因子的D结构域同源）以物种特异性方式直接参与与雌性透明带（ZP）的结合。在本研究中，我们对12种灵长类动物的47个编码外显子进行了测序，并使用最大似然法确定正向选择位点，结果表明透明带粘附素中的VWD2、膜/A5抗原μ受体和粘蛋白样结构域正在快速进化，因此可能以物种特异性方式参与灵长类动物与透明带的结合。此外，来自48个人类个体的多态性数据显示出显著的多态性与分化异质性，并且在频率谱上显著偏离平衡中性预期，这表明在人类群体中透明带粘附素（ZAN）存在平衡选择和正向选择。最后，我们观察到在一个移码突变的单倍型中存在适应性进化，该移码突变先前被认为表明ZAN是一个潜在的假基因。
