Evidence for natural selection on leukocyte immunoglobulin-like receptors for HLA class I in Northeast Asians
Evidence for natural selection on leukocyte immunoglobulin-like receptors for HLA class I in Northeast Asians
复制标题
DOI：
10.1016/j.ajhg.2008.03.012
复制
发表时间：
2008-05-01
影响因子：
9.8
通讯作者：
Yabe, Toshio
中科院分区：
文献类型：
--
作者：
Hirayasu, Kouyuki;Ohashi, Jun;Yabe, Toshio
人类白细胞抗原（HLA）在先天性和适应性免疫中起着关键作用，是自然选择下基因的一个众所周知的例子。然而，识别HLA分子的受体的遗传方面尚未完全阐明。白细胞免疫球蛋白（IG）样受体（LILR）是HLA I类识别受体的家族，包括激活和抑制形式。我们以前报道，等位基因频率的6.7 kb LILRA 3缺失是非常高的（71%）在日本人口中，我们确定了提前终止密码子（PTC）的等位基因。在这项研究中，我们观察到广泛分布的高缺失频率在东北亚洲人（84%在朝鲜族中国人，79%在满族中国人，56%在蒙古族，76%在布里亚特人）。4个HapMap群体的基因分型结果显示，LILRA 3等位基因与LILRB 2等位基因在东北亚人群中处于强连锁不平衡。此外，在东北亚人中检测到含PTC的LILRA 3等位基因，但在非东北亚人中未检测到。此外，流式细胞术分析显示，LILRB 2等位基因频繁在东北亚人显着相关的低水平的表达。F-ST和扩展单倍型纯合性分析的HapMap人群提供了积极的选择作用于LILRA 3和LILRB 2位点的证据。总之，我们的研究结果表明，在我们的研究中发现的非功能性LILRA 3等位基因和低表达LILRB 2等位基因在东北亚人中由于自然选择而增加。因此，我们的发现使我们推测，不仅HLA I类配体，而且它们的受体可能对局部环境敏感。
Human leukocyte antigen (HLA) plays a critical role in innate and adaptive immunity and is a well-known example of genes under natural selection. However, the genetic aspect of receptors recognizing HLA molecules has not yet been fully elucidated. Leukocyte immunoglobulin (Ig)-like receptors (LILRs) are a family of HLA class I-recognizing receptors comprising activating and inhibitory forms. We previously reported that the allele frequency of the 6.7 kb LILRA3 deletion is extremely high (71%) in the Japanese population, and we identified premature termination codon (PTC)-containing alleles. In this study, we observed a wide distribution of the high deletion frequency in Northeast Asians (84% in Korean Chinese, 79% in Man Chinese, 56% in Mongolian, and 76% in Buryat populations). Genotyping of the four HapMap populations revealed that LILRA3 alleles were in strong linkage disequilibrium with LILRB2 alleles in Northeast Asians. In addition, PTC-containing LILRA3 alleles were detected in Northeast Asians but not in non-Northeast Asians. Furthermore, flow-cytometric analysis revealed that the LILRB2 allele frequent in Northeast Asians was significantly associated with low levels of expression. F-ST and extended-haplotype-homozygosity analysis for the HapMap populations provided evidence of positive selection acting on the LILRA3 and LILRB2 loci. Taken together, our results suggest that both the nonfunctional LILRA3 alleles and the low-expressing LILRB2 alleles identified in our study have increased in Northeast Asians because of natural selection. Our findings, therefore, lead us to speculate that not only HLA class I ligands but also their receptors might be sensitive to the local environment.