Mhc-DRB diversity of the chimpanzee (Pan troglodytes).
Fifty-four chimpanzee Patr-DRB and five human HLA-DRB second exons were cloned and sequenced from thirty-five chimpanzees and four human B-cell lines and compared with known Mhc-DRB sequences of these two species. Equivalents of the HLA-DRB1*02, -DRB1*03, -DRB1*07 allelic lineages and the HLA-DRB3, -DRB4, -DRB5, -DRB6, and -DRB7 loci were all found in the chimpanzee. In addition, two chimpanzee Patr-DRB lineages (Patr-DRBX and -DRBY) were found for which no human counterparts have been described. None of the Patr-DRB sequences is identical to known HLA-DRB sequences. The Patr-DRB1*0702 and HLA-DRB1*0701 alleles are the most similar sequences in a comparison between the two species and differ by only two nucleotides out of 246 sequenced. Equivalents of the HLA-DRB1*01, -DRB1*04, and -DRB1*09 alleles were not found in our sample of chimpanzees. A per locus comparison of the number of Patr-DRB alleles with the HLA-DRB alleles shows that the Patr-DRB3, -DRB4, -DRB5, and -DRB6 locus are, thus far, more polymorphic than their human homologs. The polymorphism of the Patr-DRB1 locus seems to be less extensive than that reported for the HLA-DRB1 locus. Nevertheless, the Patr-DRB1 locus seems to be the most polymorphic of the Patr-DRB loci. Phylogenetic analyses indicate that the HLA-DRB1*09 allele may have originated from a recombination between a Mhc-DRB5 allele and the DRB1 allele of a Mhc-DR7 haplotype. Although recombination seems to increase the diversity of the Patr-DRB alleles, its contribution to the generation of Patr-DRB variation is probably low. Hence, most Patr-DRB diversity presumably accumulated via recurrent point mutations. Finally, two distinct Patr-DRB haplotypes are deduced, one of which (the chimpanzee equivalent of the HLA-DR7 haplotype) is probably older than 6-8 million years.
Kenter
M
M
ITRI-TNO, HV Rijswijk, The Netherlands.
Otting
N
N
Anholts
J
J
Jonker
M
M
Schipper
R
R
Bontrop
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D005091:Exons; D014644:Genetic Variation; D006684:HLA-DR Antigens / Q000235:genetics*; D015186:Hominidae / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000145:classification / Q000235:genetics / Q000276:immunology*; D010802:Phylogeny; D016415:Sequence Alignment; D013045:Species Specificity
D006684:HLA-DR Antigens; D004247:DNA