HLA CLASS-II LINKAGE DISEQUILIBRIUM AND HAPLOTYPE EVOLUTION IN THE CAYAPA INDIANS OF ECUADOR

DNA-based typing of the HLA class II loci in a sample of the Cayapa In dians of Ecuador reveals several lines of evidence that selection has operated to maintain and to diversify the existing level of polymorphi sm in the class II region. As has been noticed for other Native Americ an groups, the overall level of polymorphism at the DRB1, DQA1, DQB1, and DPB1 loci is reduced relative to that found in other human populat ions. Nonetheless, the relative evenness in the distribution of allele frequencies at each of the four loci points to the role of balancing selection in the maintenance of the polymorphism. The DQA1 and DQB1 lo ci, in particular, have near-maximum departures from the neutrality mo del, which suggests that balancing selection has been especially stron g in these cases. Several novel DQA1-DQB1 haplotypes and the discovery of a new DRB1 allele demonstrate an evolutionary tendency favoring th e diversification of class LI alleles and haplotypes. The recombinatio n interval between the centromeric DPB1 locus and the other class II l oci will, in the absence of other forces such as selection, reduce dis equilibrium across this region. However, nearly all common alleles wer e found to be part of DR-DP haplotypes in strong disequilibrium, consi stent with the recent action of selection acting on these haplotypes i n the Cayapa.