ANALYSIS OF HLA CLASS-II HAPLOTYPES IN THE CAYAPA INDIANS OF ECUADOR - A NOVEL DRB-I ALLELE REVEALS EVIDENCE FOR CONVERGENT EVOLUTION AND BALANCING SELECTION AT POSITION-86

PCR amplification, oligonucleotide probe typing, and sequencing were u sed to analyze the HLA class II loci (DRB1, DQA1, DQB1, and DPB1) of a n isolated South Amerindian tribe. Here we report HLA class II variati on, including the identification of a new DRB1 allele, several novel D R/DQ haplotypes, and an unusual distribution of DPB1 alleles, among th e Cayapa Indians (N=100) of Ecuador. A general reduction of HLA class II allelic variation in the Cayapa is consistent with a population bot tleneck during the colonization of the Americas. The new Cayapa DRB1 a llele, DRB108042, which arose by a G-->T point mutation in the parent al DRB10802, contains a novel Val codon (GTT) at position 86. The gen eration of DRB108042 (Val-86) from DRB1*0802 (Gly-86) in the Cayapa, by a different mechanism than the (GT-->TG) change in the creation of DRB108041 (Val-86) from DRB1*0802 in Africa, implicates selection in the convergent evolution of position 86 DR beta variants. The DRB1080 42 allele has not been found in >1,800 Amerindian haplotypes and thus presumably arose after the Cayapa separated from other South American Amerindians. Selection pressure for increased haplotype diversity can be inferred in the generation and maintenance of three new DRB108042 haplotypes and several novel DR/DQ haplotypes in this population. The DPB1 allelic distribution in the Cayapa is also extraordinary, with tw o alleles, DPB11401, a very rare allele in North American Amerindian populations, and DPB10402, the most common Amerindian DPB1 allele, co nstituting 83% of the Cayapa DPB1. These data are consistent with the postulated rapid rate of evolution as noted for the class I HLA-B locu s of other South American Indians.