Polymorphism of the HLA-B*15 group of alleles is generated following 5 lineages of evolution.

Generation of the HLA-B15 group of alleles has been analyzed using exon 1, intron 1, exon 2, intron 2, and exon 3 sequences from human and nonhuman primates. Results indicated that the 230 alleles analyzed could be grouped into 5 different lineages of evolution coming from nonhuman primate MHC-B alleles sharing characteristic nucleotide sequences. The major evolutionary mechanism of evolution in this group of alleles is the gene conversion event with the exchange of genomic sequences present in other HLA-Balleles. This evolutionary event reflects the importance of the exchanges between different genomic regions of distinct HLA-A, -B*, or -C* alleles and only 1 group of HLA-B* alleles (B*15 in the present paper). These data also correlated with the geographic distribution of the lineages postulated and with the corresponding serologic specificities (B62, -63, -71, -72, -75, -76, and -77). In conclusion, the high degree of polymorphism of 1 group of alleles has a specific and simple pathway of evolution, which could result in new insight into the study of immune system functionality, disease association studies, and anthropological studies.