DISSIMILAR EVOLUTION OF B-LOCUS VERSUS A-LOCUS AND CLASS-II LOCI OF THE HLA REGION IN SOUTH-AMERICAN INDIAN TRIBES

Native American populations have a limited HLA polymorphism compared w ith other ethnic groups. In spite of this, many novel HLA-B locus alle les, not observed in other populations, have been identified in South American tribes, and rapid evolution of this locus has been suggested. We have studied unrelated subjects of the Toba (TOE n=116), Wichi (WI G n=46) and Pilaga (PIL n=14) tribes from northeastern Argentina to in vestigate the extent of the HLA polymorphism and obtain clues of selec tive forces that may have acted in these populations. In these tribes the number of HLA alleles is small at all loci except HLA-B, which pre sents 22 alleles. Seven novel alleles were characterized including 5 o f HLA-B (B35092, B*3518, B*3519, B*4009, B*4803) 1 at HLA-A (A*0219) and 1 at DRB1 (DRB10417). All these variants may have arisen by gene conversion events. Some of the novel variants represent the most frequ ent alleles of these populations (B4803 in TOB and PIL; B*3519 in WIC ) or are the most frequent subtypes in their lineages. HLA-A, B, DRB1, DQA1 and DQB1, but not DPB1, display relatively similar gene frequenci es. This results in high heterozygosity in all the tribes for all the loci studied except HLA-DPB1. The larger polymorphism and the generati on and maintenance of novel alleles at the HLA-B locus suggests a more specialized response of this locus to evolutionary forces. These effe cts may be related to the nature of the polymorphism, to the number of founder alleles and to the functional characteristics of the individu al alleles.