Aarts H J, den Dunnen J T, Leunissen J, Lubsen N H, Schoenmakers J G
Laboratory of Molecular Biology, University of Nijmegen, The Netherlands.
J Mol Evol. 1988;27(2):163-72. doi: 10.1007/BF02138377.
The gamma-crystallin proteins consist of two topologically equivalent domains, each built up out of two similar motifs. They are encoded by a gene family, which already contained five members before the divergence of rodents and primates. A further gene duplication took place in each lineage. To analyze the pattern of evolution within this gene family, the coding sequences of six human genes, six rat genes, and four mouse genes were compared. Between species, a uniform rate of evolution of all regions of the protein is seen. The ratio of synonymous to nonsynonymous substitution in the human/rat or human/mouse comparison is much lower than the ratio when rat and mouse are compared indicating that the gamma-crystallin proteins are better conserved in the rodent lineage. Within species, the regions encoding the two external motifs I and III of the protein show a greater extent of nonsynonymous substitution than the regions encoding the two internal protein motifs II and IV. The low extent of synonymous substitution between the second exons (encoding motifs I and II) of the rat gamma-crystallin genes suggests the frequent occurrence of gene conversion. In contrast, a high extent of synonymous substitution is found in exon 3 (encoding motifs III and IV) of the rat genes. The same phenomenon is seen within the human gene family. The frequencies of occurrence of the various dinucleotides deviate less from those predicted from the frequencies of occurrence of each individual nucleotide in the second exons than in the third exons. The sequences of the third exons are significantly depleted in CpG, ApA, and GpT and enriched in CpT and GpA.
γ-晶体蛋白由两个拓扑结构等效的结构域组成，每个结构域由两个相似的基序构成。它们由一个基因家族编码，在啮齿动物和灵长类动物分化之前，该家族就已经包含五个成员。每个谱系中又发生了一次基因复制。为了分析这个基因家族的进化模式，对六个人类基因、六个大鼠基因和四个小鼠基因的编码序列进行了比较。在不同物种之间，可以看到蛋白质所有区域的进化速率是一致的。在人与大鼠或人与小鼠的比较中，同义替换与非同义替换的比率远低于大鼠和小鼠比较时的比率，这表明γ-晶体蛋白在啮齿动物谱系中保守性更好。在同一物种内，编码蛋白质两个外部基序I和III的区域比编码两个内部蛋白质基序II和IV的区域表现出更大程度的非同义替换。大鼠γ-晶体蛋白基因第二个外显子（编码基序I和II）之间同义替换的程度较低，这表明基因转换频繁发生。相比之下，在大鼠基因的外显子3（编码基序III和IV）中发现了高度的同义替换。在人类基因家族中也观察到了同样的现象。与第三个外显子相比，第二个外显子中各种二核苷酸的出现频率与根据每个单独核苷酸出现频率预测的值的偏差较小。第三个外显子的序列中CpG、ApA和GpT显著减少，而CpT和GpA则富集。
