Herlyn Holger, Zischler Hans
Institute of Anthropology, University of Mainz, Germany.
Mol Phylogenet Evol. 2005 Oct;37(1):62-72. doi: 10.1016/j.ympev.2005.04.001.
Positive selection has been shown to be pervasive in sex-related proteins of many metazoan taxa. However, we are only beginning to understand molecular evolutionary processes on the lineage to humans. To elucidate the evolution of proteins involved in human reproduction, we studied the sequence evolution of MAM domains of the sperm-ligand zonadhesin in respect to single amino acid sites, solvent accessibility, and posttranslational modification. GenBank-data were supplemented by new cDNA-sequences of a representative non-human primate panel. Solvent accessibility predictions identified a probably exposed fragment of 30 amino acids belonging to MAM domain 2 (i.e., MAM domain 3 in mouse). The fragment is characterized by significantly increased rate of positively selected amino acid sites and exhibits high variability in predicted posttranslational modification, and, thus, might represent a binding region in the mature protein. At the same time, there is a significant coincidence of positively selected amino acid sites and non-conserved posttranslational motifs. We conclude that the binding specificity of zonadhesin MAM domains, especially of the presumed epitope, is achieved by positive selection at the level of single amino acid sites and posttranslational modifications, respectively.
正向选择已被证明在许多后生动物类群的与性相关的蛋白质中普遍存在。然而，我们才刚刚开始了解人类谱系上的分子进化过程。为了阐明参与人类生殖的蛋白质的进化，我们研究了精子配体zonadhesin的MAM结构域在单个氨基酸位点、溶剂可及性和翻译后修饰方面的序列进化。GenBank数据由一个代表性的非人类灵长类动物组的新cDNA序列补充。溶剂可及性预测确定了属于MAM结构域2（即小鼠中的MAM结构域3）的一个可能暴露的30个氨基酸的片段。该片段的特征是正向选择的氨基酸位点的速率显著增加，并且在预测的翻译后修饰中表现出高变异性，因此可能代表成熟蛋白质中的一个结合区域。同时，正向选择的氨基酸位点与非保守的翻译后基序存在显著重合。我们得出结论，zonadhesin MAM结构域，尤其是假定表位的结合特异性，分别通过单个氨基酸位点水平的正向选择和翻译后修饰来实现。
