EPISODIC EVOLUTION AND TURNOVER OF HLA-B IN THE INDIGENOUS HUMAN-POPULATIONS OF THE AMERICA

Nucleotide sequences were determined for the HLA-A, B and C alleles of three populations of Amerindians: the Havasupai tribe from North Amer ica, and the Guarani and Kaingang tribes from South America. All 15 Ha vasupai alleles are found in Eastern Hemisphere populations, whereas t he Guarani and Kaingang each have six alleles that appear to be presen t only in the Western Hemisphere. Nine of the ''new'' alleles come fro m HLA-B, one comes from HLA-A and one from HLA-C: ten appear to be the result of recombination and one the result of point substitution. Of the 14 Guarani alleles and 16 Kaingang alleles, only four are held in common. Despite their differences, the three tribes possess comparable numbers of HLA class I alleles, revealing a trend for ''allele turnov er'', in which new alleles tends to supplant older alleles rather than supplement them. Although many new HLA-B alleles have been produced i n Latin America, their net effect has been to differentiate population s, not to increase allele diversity within a population. From sequence comparisons, the Amerindian subset of HLA class I allotypes appears t o cover the overall ranges of peptide binding specificity, natural kil ler-cell interactions, and CD8 interactions, that are found in all HLA class I. The recombinations that produced the new alleles of the Kain gang and Guarani class I are predicted to have modulated these functio nal properties rather than radically change them. Exchange of Bw4 and Bw6 motifs by recombination are noticeably absent in the events formin g new alleles in America, whereas they have been the most common of re combinations elsewhere.