Global diversity and evidence for coevolution of KIR and HLA.
The killer immunoglobulin-like receptor (KIR) gene cluster shows extensive genetic diversity, as do the HLA class I loci, which encode ligands for KIR molecules. We genotyped 1,642 individuals from 30 geographically distinct populations to examine population-level evidence for coevolution of these two functionally related but unlinked gene clusters. We observed strong negative correlations between the presence of activating KIR genes and their corresponding HLA ligand groups across populations, especially KIR3DS1 and its putative HLA-B Bw4-80I ligands (r = -0.66, P = 0.038). In contrast, we observed weak positive relationships between the various inhibitory KIR genes and their ligands. We observed a negative correlation between distance from East Africa and frequency of activating KIR genes and their corresponding ligands, suggesting a balance between selection on HLA and KIR loci. Most KIR-HLA genetic association studies indicate a primary influence of activating KIR-HLA genotypes in disease risk; concomitantly, activating receptor-ligand pairs in this study show the strongest signature of coevolution of these two complex genetic systems as compared with inhibitory receptor-ligand pairs.
Single
Richard M
RM
The Department of Mathematics and Statistics, University of Vermont, Burlington, Vermont 05405, USA.
Martin
Maureen P
MP
Gao
Xiaojiang
X
Meyer
Diogo
D
Yeager
Meredith
M
Kidd
Judith R
JR
Kidd
Kenneth K
KK
Carrington
Mary
M
D000483:Alleles; D019143:Evolution, Molecular; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D054349:Receptors, KIR3DS1 / Q000235:genetics
D006680:HLA Antigens; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1