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 acids at specific sites. Variation was surveyed at 4
loci (DRB1, DQA1, DQB1, and 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. Substantial variations in polymorphism
were observed among the various populations and loci studied. In the majority of the
populations, DRB1 has the highest heterozygosity and effective number of alleles. As previously
shown, the Amerindian populations have lower levels of allelic diversity when compared to other
populations. At the amino acid level, DRB1 antigen recognition sites (ARS) have the highest
heterozygosities and effective number of alleles. For the other loci (DPB1, DQA1, and DQB1) for
which there is no crystal structure and for which ARS sites were inferred from DRB1, non-ARS sites
were often 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 data. Of the four HLA
class II loci studied, only DPB1 failed to show evidence of balancing selection. DQB1 and DQA1
depart significantly from neutrality in the largest number of populations. Genetic distances between
populations were computed based on frequency of alleles and amino acids at ARS sites.