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Unparalleled Rapid Evolution of KIR Genes in Rhesus and Cynomolgus Macaque Populations
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-02-28 , DOI: 10.4049/jimmunol.1901140
Jesse Bruijnesteijn , Nanine de Groot , Marit K. H. van der Wiel , Nel Otting , Annemiek J. M. de Vos-Rouweler , Natasja G. de Groot , Ronald E. Bontrop

Key Points KIR genes evolved rapidly in closely related macaque species and their populations. Hybrid KIR genes in macaques are generated frequently by recombination. The killer cell Ig-like receptors (KIR) modulate immune responses through interactions with MHC class I molecules. The KIR region in large cohorts of rhesus and cynomolgus macaque populations were characterized, and the experimental design enabled the definition of a considerable number of alleles (n = 576) and haplotypes, which are highly variable with regard to architecture. Although high levels of polymorphism were recorded, only a few alleles are shared between species and populations. The rapid evolution of allelic polymorphism, accumulated by point mutations, was further confirmed by the emergence of a novel KIR allele in a rhesus macaque family. In addition to allelic variation, abundant orthologous and species-specific KIR genes were identified, the latter of which are frequently generated by fusion events. The concerted action of both genetic mechanisms, in combination with differential selective pressures at the population level, resulted in the unparalleled rapid evolution of the KIR gene region in two closely related macaque species. The variation of the KIR gene repertoire at the species and population level might have an impact on the outcome of preclinical studies with macaque models.

中文翻译:

恒河猴和食蟹猴种群中 KIR 基因无与伦比的快速进化

关键点 KIR 基因在密切相关的猕猴物种及其种群中进化迅速。猕猴中的杂交 KIR 基因经常通过重组产生。杀伤细胞 Ig 样受体 (KIR) 通过与 MHC I 类分子的相互作用调节免疫反应。对大型恒河猴和食蟹猴种群中的 KIR 区域进行了表征,并且实验设计能够定义相当数量的等位基因 (n = 576) 和单倍型,这些基因在结构方面具有高度可变性。尽管记录了高水平的多态性,但物种和种群之间只有少数等位基因共享。由点突变积累的等位基因多态性的快速进化,在恒河猴家族中出现了一个新的 KIR 等位基因,进一步证实了这一点。除了等位基因变异外,还鉴定了丰富的直系同源和物种特异性 KIR 基因,后者经常由融合事件产生。两种遗传机制的协同作用,再加上种群水平上的不同选择压力,导致了两个密切相关的猕猴物种中 KIR 基因区域的无与伦比的快速进化。KIR 基因库在物种和种群水平上的变化可能会对猕猴模型的临床前研究结果产生影响。导致 KIR 基因区域在两个密切相关的猕猴物种中无与伦比的快速进化。KIR 基因库在物种和种群水平上的变化可能会对猕猴模型的临床前研究结果产生影响。导致 KIR 基因区域在两个密切相关的猕猴物种中无与伦比的快速进化。KIR 基因库在物种和种群水平上的变化可能会对猕猴模型的临床前研究结果产生影响。
更新日期:2020-02-28
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