Modi W S, Yoshimura T
Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Mol Biol Evol. 1999 Feb;16(2):180-93. doi: 10.1093/oxfordjournals.molbev.a026101.
Approximately 15 different alpha, or CXC, chemokines have thus far been isolated from 11 species of mammals. Among the best studied chemokines are the 12 human proteins that are encoded by 11 paralogous genes. In order to better understand the evolution and function of this group of genes, we isolated and characterized six novel GRO and GRO-related cDNA sequences from the cow (Bos taurus), the sheep (Ovis aries), the rabbit (Oryctolagus cuniculus), and the guinea pig (Cavia porcellus). The amino acid sequence of the diverged guinea pig GRO or KC gene is only 50%-60% similar to presumed orthologs from other species, while the sheep and cow GRO proteins are 90%-99% similar to each other. The presence of multiple GRO genes in the cow, the rabbit, and the sheep is consistent with what has been observed for humans. Phylogenetic analyses of amino acid sequences from 44 proteins indicate that genes orthologous to many of the 11 known from humans exist in other species. One such gene, interleukin 8, or IL8, has been isolated from nine species, including the rodent guinea pig; however, this gene is absent in the rat and the mouse, indicating a unique gene loss event in the rat/mouse (muroid rodent) lineage. The KC (or MIP2) gene of rodents appears to be orthologous to the GRO gene found in other taxonomic orders. Combined evidence from different sources suggests that IP10 and MIG share sister taxon relationships on the evolutionary tree, while the remaining paralogous genes represent independent lineages, with limited evidence for kinship between them. This observation indicates that these genes originated nearly contemporaneously via a series of gene duplication events. Relative-rate tests for synonymous and nonsynonymous nucleotide substitutions in the KC and IL8 genes did not detect rate heterogeneity; however, there are several notable features regarding the IL8 genes. For example, the IL8 proteins from two Old World monkeys are as similar to one another as they are to the IL8 protein from humans, and all observed nucleotide differences between the IL8 genes of the two monkeys cause amino acid changes; in other words, there are no synonymous differences between them.
迄今为止，已从11种哺乳动物中分离出约15种不同的α或CXC趋化因子。在研究得较为深入的趋化因子中，有12种人类蛋白质由11个旁系同源基因编码。为了更好地理解这组基因的进化和功能，我们从牛（Bos taurus）、绵羊（Ovis aries）、兔子（Oryctolagus cuniculus）和豚鼠（Cavia porcellus）中分离并鉴定了6个新的GRO及GRO相关的cDNA序列。分化后的豚鼠GRO或KC基因的氨基酸序列与其他物种的假定直系同源物只有50%-60%的相似性，而绵羊和牛的GRO蛋白彼此之间有90%-99%的相似性。牛、兔子和绵羊中存在多个GRO基因，这与在人类中观察到的情况一致。对44种蛋白质的氨基酸序列进行系统发育分析表明，在其他物种中存在许多与人类已知的11种基因直系同源的基因。其中一个这样的基因，即白细胞介素8（IL8），已从包括啮齿动物豚鼠在内的9个物种中分离出来；然而，该基因在大鼠和小鼠中不存在，这表明在大鼠/小鼠（鼠形啮齿动物）谱系中发生了独特的基因丢失事件。啮齿动物的KC（或MIP2）基因似乎与其他分类目中发现的GRO基因直系同源。来自不同来源的综合证据表明，IP10和MIG在进化树上具有姐妹分类群关系，而其余的旁系同源基因代表独立的谱系，它们之间亲缘关系的证据有限。这一观察结果表明，这些基因通过一系列基因复制事件几乎同时起源。对KC和IL8基因中同义与非同义核苷酸替换的相对速率测试未检测到速率异质性；然而，IL8基因有几个显著特征。例如，两只旧世界猴的IL8蛋白彼此之间的相似程度与它们与人类IL8蛋白的相似程度相同，并且观察到的两只猴的IL8基因之间的所有核苷酸差异都会导致氨基酸变化；换句话说，它们之间没有同义差异。
