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

Abstract

The allele frequency distributions for the HLA class II loci, DRB1, DQB1 and 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-specific oligonucleotide probe (PCR/SSOP) typing methods. The allele frequency distributions for the HLA-DRB1 locus were determined for a third Indonesian population 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. The DRB1*1502 allele is frequent in nine of the ten populations studied, reaching a frequency of 0.48 in one Indonesian population and among Filipinos. Extensive DR-DQ haplotype diversity was detected in these populations. Seven different DR2-DQB1 haplotypes were observed in the Indonesian and PNG Lowland populations, eight in the PNG Highlands and ten in Malays and Filipinos. 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 populations. Two additional DRB1 alleles commonly observed in Australia, DRB1*0405 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 0.013). These alleles are generally rare or absent in the other populations. The DPB1*0501 allele, common in Chinese and Japanese populations, is most frequent 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 Highlands. Analyses of homozygosity (the Ewens-Watterson F statistic) in these and other populations indicate that, while most allele frequency distributions are consistent with balancing selection, values of F for the Indonesian and Javan populations may reflect positive directional selection. Phylogenetic 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 more closely related to Australian populations than to PNG Lowland populations, while the PNG Lowlands are more closely related to other Melanesian populations.

Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

“…These studies found similar allele distribution patterns for most populations and loci. As with Native American populations (described above), the degree of differentiation was higher among populations from southeast Asia, Polynesia, Melanesia and Australia [35][36][37][38][39][40] than the rest of the world, and populations from these areas display reduced diversity in allelic lineages. The distribution of HLA alleles in 'island type' populations also resembled the ones described above for Native Americans; in the populations from Oceania, the DRB1 locus has more allelic lineages and appears to present higher degrees of differentiation.…”

Balancing selection and heterogeneity across the classical human leukocyte antigen loci: A meta-analytic review of 497 population studies

“…Again, the differences can be explained by the small number of populations being averaged and the correspondingly large influence of outliers (such as the Javanese and Indonesian populations) in the Salamon et al study. Mack et al [4] concluded that the high F nd values observed in these OCE outlier populations were the result of selection in response to a local pathogen. Valdes et al [226] examined variation of class II loci, considered at the locus and amino acid level, in 22 populations from the 12th IHW, with similar results to those of the Salamon et al study.…”

“…Population-level studies of HLA allelic diversity have provided insight into the selective forces that have acted to generate and maintain polymorphism in the human species [2,3]. Historical and evolutionary relationships among modern human populations have been inferred from comparisons of HLA allele and haplotype frequency distributions [4][5][6][7]. Further, variation in the allelic diversity between populations, as well as comparisons of linkage disequilibrium (LD) patterns across the HLA region, have been used to infer demographic events such as bottlenecks and founder events [3,8].…”

The evolutionary ecology of the major histocompatibility complex

“…Watterson (1978) proposed that deviation from such an equilibrium is an indicator of departures from neutrality and hence selection. The so-called Ewens-Watterson test of neutrality has been used to confirm the effects of balancing selection acting on the MHC in both non-model species (Paterson, 1998;Miller et al, 2001;Hambuch and Lacey, 2002) and humans (Mack et al, 2000;Begovich et al, 2001).…”