Evolution of Pacific/Asian populations inferred from HLA class II allele frequency distributions

The allele frequency distributions for the HLA class II loci, DRB1, DQB1 an d DPB1, in eight Pacific/Asian populations: Hawaiian, Samoan, Malay, Papua New Guinea (PNG) Highlands, and two Indonesian and PNG Lowland groups, were determined using high-resolution polymerase chain reaction/sequence-specif ic oligonucleotide probe (PCR/SSOP) typing methods. The allele frequency di stributions for the HLA-DRB1 locus were determined for a third Indonesian p opulation as well as for an additional Filipino population. DRB1 alleles in the DR2 serogroup (or allelic lineage) are very common in this region; in some populations, more than 50% of the alleles belong to this serogroup. Th e DRB1*1502 allele is frequent in nine of the ten populations studied, reac hing a frequency of 0.48 in one Indonesian population and among Filipinos. Extensive DR-DQ haplotype diversity was detected in these populations. Seve n different DR2-DQB1 haplotypes were observed in the Indonesian and PNG Low land populations, eight in the PNG Highlands and ten in Malays and Filipino s. The DRB1*0410 allele, commonly observed in Australia, is observed in the PNG Highlands at a low frequency (f=0.03) and is absent in the other popul ations. Two additional DRB1 alleles commonly observed in Australia, DRB1"04 05 and *1407, are also observed in the PNG Highlands at high frequencies (f =0.132 and 0.126), while they are rare in the PNG Lowlands (f=0.039 and 0.0 13). These alleles are generally rare or absent in the other populations. T he DPB1*0501 allele, common in Chinese and Japanese populations, is most fr equent in the Samoan, Hawaiian, Indonesian, and Malay populations, and the "0401 allele is the most frequent DPB1 allele in the PNG Lowlands. Both of these alleles have the same very high frequency (f =0.34) in the PNG Highla nds. Analyses of homozygosity (the Ewens-Watterson F statistic) in these an d other populations indicate that, while most allele frequency distribution s are consistent with balancing selection, values of F for the Indonesian a nd Javan populations may reflect positive directional selection. Phylogenet ic trees constructed using the allele frequencies at the DRB1 locus of the populations reported here, as well as those for additional Pacific, Asian, and Australian populations, indicate that the PNG Highland population is mo re closely related to Australian populations than to PNG Lowland population s, while the PNG Lowlands are more closely related to other Melanesian popu lations.