title: Evidence for natural selection on leukocyte immunoglobulin-like receptors for HLA class I in Northeast Asians.
abstract: 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.
authors.affiliation: Tokyo Metropolitan Red Cross Blood Center, Tokyo 135-8639, Japan.
authors.forename: Kouyuki
authors.initials: K
authors.lastname: Hirayasu
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Kashiwase
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ogawa
authors.forename: Minoko
authors.initials: M
authors.lastname: Takanashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Satake
authors.forename: Guan Jun
authors.initials: GJ
authors.lastname: Jia
authors.forename: Nyam-Osor
authors.initials: NO
authors.lastname: Chimge
authors.forename: Elena W
authors.initials: EW
authors.lastname: Sideltseva
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Toshio
authors.initials: T
authors.lastname: Yabe
mesh_terms: D044466:Asian People; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D015395:Histocompatibility Antigens Class I; C530062:LILRA3 protein, human; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic