Definition of the cattle killer cell Ig-like receptor gene family: comparison with aurochs and human counterparts.
Definition of the cattle killer cell Ig-like receptor gene family: comparison with aurochs and human counterparts.
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DOI：
10.4049/jimmunol.1401980
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发表时间：
2014-12-15
期刊：
影响因子：
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通讯作者：
Hammond JA
中科院分区：
文献类型：
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作者：
Sanderson ND;Norman PJ;Guethlein LA;Ellis SA;Williams C;Breen M;Park SD;Magee DA;Babrzadeh F;Warry A;Watson M;Bradley DG;MacHugh DE;Parham P;Hammond JA
在病原体的选择压力下，识别多态性MHC I类的可变NK细胞受体在不同物种的胎盘哺乳动物中趋同进化。出乎意料的是，多样化的杀伤细胞免疫球蛋白样受体（KIR）是由猿类灵长类动物，包括人类和牛，但不是由其他物种共享。尽管对人类KIR遗传学和基因组学的了解很多，但对牛KIR的了解仅限于9个cDNA序列。为了便于比较牛和人类KIR基因家族，我们确定了两个牛KIR单倍型的基因组位置，结构和序列，并定义了野牛（已灭绝的野生祖先）的KIR序列。牛的KIR基因座比人类的KIR基因座大，它是通过连续复制一个含有祖先KIR3DL和KIR3DX基因的基因块进化而来的，这些基因块存在于胎盘哺乳动物之前。两种黄牛KIR单倍型与欧洲野牛KIR的比较表明，KIR具有多态性，基因组结构和基因内容具有保守性。在18个基因中，8个是功能性的，10个被点突变失活。KIR3DL和活化受体基因的选择性失活留下一个抑制性KIR3DL、一个活化性KIR3DX和六个抑制性KIR3DX的功能群组。功能性KIR多样性在牛中从KIR3DX进化而来，在猿类灵长类中从KIR3DL进化而来。虽然是独立进化的，但牛和人KIR基因家族具有重要的功能相关特性，表明牛KIR是牛MHC I类的NK细胞受体。KIR和MHC I类的结合是与人类疾病相关的主要遗传因子，值得在牛中进行研究。
Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig–like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle.