Genetic exchange in the evolution of the human MHC class II loci

A total of 61 DNA sequences from human major histocompatibility class II loci were searched for statistical evidence of past genetic exchange (gene conversion or recombination). Among the 12 A-locus sequences (derived from DPA1 and DQA1), 4 clusters indicating potential exchange events were found. Among the 49 B-locus sequences (derived from DOB, DPB1, DPB2, DQB1, DRB1, DRB3, DRB4 and DRB5), 15 clusters were found. The clusters suggested short exchanges (less than 100 bp) within and between loci, and were concentrated in exon 2 (coding for the antigen binding site). The most striking feature of the results was the presence of an approximately 200-bp region in the middle of B-locus exon 2 which contained almost no locus-specific substitutions, which were abundant elsewhere. This suggests either strong selection for locus specificity in the other regions of the gene or a history of frequent between-locus exchange in this part of exon 2, which is involved in forming the antigen binding site.