Blokhuis Jeroen H, Doxiadis Gaby G M, Bontrop Ronald E
Biomedical Primate Research Centre, Department of Comparative Genetics and Refinement, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands.
Mol Immunol. 2009 Feb;46(4):640-8. doi: 10.1016/j.molimm.2008.08.270. Epub 2008 Nov 18.
The killer cell Ig-like receptor (KIR) 3DH protein in rhesus macaques (Macaca mulatta) is thought to be an activating one because it contains a charged arginine in its transmembrane domain and has a truncated cytoplasmic domain. MmKIR3DH has thus far been characterized by an analysis of cDNA. Its presence and polymorphism has been further investigated by examining mRNA transcripts and genomic sequences in families. Multiple copies of MmKIR3DH are present per animal, suggesting that the gene has been duplicated on some haplotypes. All transcripts are truncated and lack exon 8. Investigation of the gene itself shows that exon 8 is present, intact, and homologous to MmKIR2DL4. However, there is a mutation in the donor splice site of intron 8, which is absent in MmKIR2DL4 genomic sequences. This mutation introduces a frameshift, subsequently resulting in a premature stopcodon. To further verify this mutation, a cohort of unrelated animals from different geographical locations was examined, and both exon 8 and the splice site mutation were seen to be present in their MmKIR3DH genes. The data suggest that the splice site mutation causes the truncation of the MmKIR3DH transcript and the subsequent loss of its inhibitory motifs further downstream. Loss of inhibitory potential through different mutations is observed in other primate species as well, suggesting convergent evolution; however, this is the first report to document that a mutation in an intron produces a similar effect.
恒河猴（猕猴属）中的杀伤细胞免疫球蛋白样受体（KIR）3DH蛋白被认为是一种激活型蛋白，因为它在跨膜结构域含有一个带电荷的精氨酸，并且其胞质结构域被截短。到目前为止，MmKIR3DH已通过对cDNA的分析进行了表征。通过检查家族中的mRNA转录本和基因组序列，进一步研究了它的存在和多态性。每只动物体内都存在多个MmKIR3DH拷贝，这表明该基因在某些单倍型上发生了复制。所有转录本都被截短且缺少外显子8。对该基因本身的研究表明外显子8是存在的、完整的，并且与MmKIR2DL4同源。然而，内含子8的供体剪接位点存在一个突变，该突变在MmKIR2DL4基因组序列中不存在。这种突变导致了移码，随后产生了一个提前终止密码子。为了进一步验证这种突变，对来自不同地理位置的一组无亲缘关系的动物进行了检查，发现它们的MmKIR3DH基因中都存在外显子8和剪接位点突变。数据表明，剪接位点突变导致了MmKIR3DH转录本的截短以及其下游抑制基序的后续缺失。在其他灵长类物种中也观察到通过不同突变导致的抑制潜力丧失，这表明存在趋同进化；然而，这是第一份记录内含子突变产生类似效应的报告。
