HLA-DR and -DQ Gene Polymorphism in West Africans is Twice as Extensive as in North European Caucasians: Evolutionary Implications

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-10, Vol.88 (19), p.8480-8484
• Main Authors: Olerup, Olle, Troye-Blomberg, Marita, Schreuder, G. M. T., Riley, Eleanor M.
• Format: Article
• Language: English
• Subjects: Africa, Western; African Continental Ancestry Group - genetics; Alleles; Biological and medical sciences; Biological Evolution; Classical genetics, quantitative genetics, hybrids; Ethnic groups; Europe; European Continental Ancestry Group - genetics; Evolution; Evolutionary genetics; Fundamental and applied biological sciences. Psychology; Gene Frequency; genes; Genetic loci; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; histocompatibility antigen HLA-DQ; HLA antigens; HLA-DQ Antigens - genetics; HLA-DR Antigens - genetics; Human; Human genetics; Humans; Major Histocompatibility Complex; Medical genetics; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; restriction fragment length polymorphism; West Africa; White people
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.19.8480

The HLA genes are the most polymorphic coding loci known in humans. DRB-DQA-DQB gene polymorphism was investigated by Taq I restriction fragment length polymorphism analysis in more than 700 West Africans and found to be almost twice as extensive in West Africans as in North European Caucasians. This finding indicates that Africans comprise the oldest and genetically most diverse human population and supports the hypothesis of the occurrence of a population bottleneck in the emergence of the White race. As in Caucasians, less than one-third of possible cis-encoded DQA-DQB combinations were encountered, indicating constraints on the pairing of DQ α and β polypeptides. Heterozygote advantage (i.e., positive selection) was found for DRB, DQA, and DQB alleles as well as for DQA-DQB combinations. However, in West Africans as well as in North Europeans the observed frequencies of DRB-DQA-DQB homozygotes were close to neutrality expectations. Although the hypothesis that HLA polymorphism is maintained by parasite-driven over-dominant selection is attractive, there is little evidence to support that view. We propose instead that one of the forces maintaining a low frequency of HLA homozygotes might be a decreased likelihood of potentially autoreactive T-cell clones escaping thymic selection in HLA heterozygotes. This would be consistent with the central role of HLA molecules as self/nonself discriminators