Population genetic studies of HLA-E: evidence for selection.

HLA-E is a nonclassical, class I gene (Ib) of unknown function. The study was initiated to determine the amount and nature of the variation in the class Ib gene HLA-E in diverse ethnic groups. A single base-pair substitution (A-->G at 382, exon 3) resulting in a change from an arginine (R) to a glycine (G) at codon 107 was found. A glycine was present at position 107 in individuals from four ape species, suggesting that EG107 is the older of the two alleles. The two human alleles were present in all samples studied. The alleles were in linkage disequilibrium with HLA-A (W = 0.58), HLA-B (W = 0.59) and HLA-C (W = 0.55) in the Hutterites. The frequencies of the two HLA-E alleles were more equal than expectations based on neutrality in inbred and outbred Caucasian samples (Watterson's F = 0.506, p = 0.02 and F = 0.512, p = 0.047, respectively) and nearly significant in African-American and Hispanic samples (F = 0.513, p = 0.063 and F = 0.508, p = 0.053). These data suggest that this polymorphism arose before the expansion of Homo sapiens and has been maintained in diverse populations by stabilizing selection.