Locus and population specific evolution in HLA class II genes

The population genetics of the HLA class II loci was studied with reference to variation in the frequency of (a) alleles at a locus and (b) amino acid s at specific sites. Variation was surveyed at 4 loci (DRB1, DQA1, DQB1, an d DPB1) in 22 populations from the Twelfth International Histocompatibility Workshop (Saint-Malo, 1996). Allele and amino acid variation was measured by computing heterozygosity and the effective number of alleles. Substantia l variations in polymorphism were observed among the various populations an d loci studied. In the majority of the populations, DRB1 has the highest he terozygosity and effective number of alleles. As previously shown, the Amer indian populations have lower levels of allelic diversity when compared to other populations. At the amino acid level, DRB1, antigen recognition sites (BRS) have the highest heterozygosities and effective number of alleles. F or the other loci (DPB1, DQA1, and DQB1) for which there is no crystal stru cture and for which ARS sites were inferred from DRB1, non-ARS sites were o ften among the sites with highest levels of variation. It is possible that these putative non-ARS sites do play a role in antigen presentation. The homozygosity test for neutrality was applied to allele and amino acid d ata. Of the four HLA class II loci studied, only DPB1 failed to show eviden ce of balancing selection. DQB1 and DQA1. depart significantly from neutral ity in the largest number of populations. Genetic distances between populat ions were computed based on frequency of alleles and amino acids at ARS sit es.