Hao Li, Nei Masatoshi
Institute of Molecular Evolutionary Genetics and Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.
Gene. 2005 Mar 14;347(2):149-59. doi: 10.1016/j.gene.2004.12.012. Epub 2005 Feb 19.
The gene family of killer cell immunoglobulin-like receptors (KIRs) in primates provides the first line of defense against virus infection and tumor transformation. Interacting with MHC class I molecules, KIRs can regulate the cytotoxic activity of natural killer (NK) cells and distinguish the tumor and virus infected cells from normal body cells. Phylogenetic analysis and comparison of domain structures identified three major groups of KIR genes (group I, II, and III genes). These groups of KIR genes, generated by a series of gene duplications, have acquired different MHC-binding specificity. Inference of ancestral KIR sequences suggested that the functional divergence of group I genes from group II genes occurred by positive selection at the MHC-binding sites after duplication. Our evolutionary study has shown that group I genes diverged from group II genes about 17 million years ago (Mya) apparently after separation of hominoids from Old World (OW) monkeys. Around the same time, gene duplication generating the class I MHC-C locus appears to have occurred. These findings suggest that KIR and MHC class I genes have coevolved as an interacting system. The KIR gene family has experienced a rapid expansion in primate species. The rate of expansion of this gene family seems to be one of the highest among all hominoid gene families. The KIR gene family is also subject to birth-and-death evolution.
灵长类动物中的杀伤细胞免疫球蛋白样受体（KIR）基因家族为抵御病毒感染和肿瘤转化提供了第一道防线。KIR与MHC I类分子相互作用，可调节自然杀伤（NK）细胞的细胞毒性活性，并区分肿瘤细胞和病毒感染细胞与正常体细胞。通过系统发育分析和结构域结构比较，确定了KIR基因的三个主要类别（I组、II组和III组基因）。这些通过一系列基因复制产生的KIR基因类别，获得了不同的MHC结合特异性。对祖先KIR序列的推断表明，I组基因与II组基因在功能上的差异是在复制后通过MHC结合位点的正选择而发生的。我们的进化研究表明，I组基因大约在1700万年前（Mya）与II组基因发生分歧，显然是在类人猿与旧世界（OW）猴分离之后。大约在同一时间，产生I类MHC-C基因座的基因复制似乎已经发生。这些发现表明，KIR和MHC I类基因作为一个相互作用的系统共同进化。KIR基因家族在灵长类物种中经历了快速扩张。这个基因家族的扩张速度似乎是所有类人猿基因家族中最高的之一。KIR基因家族也经历了生死进化。
