HLA CLASS-II ALLELES IN AMERINDIAN POPULATIONS - IMPLICATIONS FOR THEEVOLUTION OF HLA POLYMORPHISM AND THE COLONIZATION OF THE AMERICA

The analysis of HLA allele frequencies in various Amerindian populatio ns may shed light on the history of human migrations in the Americas; the overall reduction in the number of alleles relative to non-Amerind ian populations and the observation that the same alleles and allelic lineages are ''missing'' in all Amerindian groups suggests an ''Into A merica'' population bottleneck. The identification of previously unrep orted (and presumably newly arisen) HLA-DRB1 alleles among isolated Am erindian groups, (DRB0417 in Argentina, *08042 in Ecuador, DRB1*0807 in Brazil, and 0811 in Canada) suggests that these alleles may have b een generated since the colonization of the Americas (about 20-30,000 years ago). These observations are difficult to reconcile with the not ion, based on the analysis of exon-2 sequences, that most of the human DRB1 alleles are ''ancient'', that is, predate the divergence of the hominoids (4-7 myr). Recent analyses of DRB1 intron sequences, however , indicate that, although most of the allelic lineages are ancient, th e alleles within a lineage (>90% of the DRB1 alleles) have arisen rela tively recently. For DRB10807, presumably generated by an Asp to Val change (GAT to GTT) at codon 57, strong selective pressures appear to be in operation, based on the high frequency (23%), and linkage disequ ilibrium patterns of this allele. The analysis of a complex microsatel lite in the second intron in the Ticuna is consistent with the notion that the new Amerindian DR8 alleles arose from DRB10802, the only DR8 allele observed in most Amerindian populations.