Kenter M, Otting N, Anholts J, Jonker M, Schipper R, Bontrop R E
ITRI-TNO, HV Rijswijk, The Netherlands.
Immunogenetics. 1992;37(1):1-11. doi: 10.1007/BF00223539.
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-DRB102, -DRB103, -DRB107 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-DRB10702 and HLA-DRB10701 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-DRB101, -DRB104, and -DRB109 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.
从35只黑猩猩和4个人类B细胞系中克隆并测序了54个黑猩猩Patr - DRB和5个人类HLA - DRB第二外显子,并与这两个物种已知的Mhc - DRB序列进行了比较。在黑猩猩中发现了与HLA - DRB102、- DRB103、- DRB107等位基因谱系以及HLA - DRB3、- DRB4、- DRB5、- DRB6和- DRB7基因座相对应的序列。此外,还发现了两个黑猩猩Patr - DRB谱系(Patr - DRBX和- DRBY),尚未发现其对应的人类序列。没有一个Patr - DRB序列与已知的HLA - DRB序列相同。在两个物种的比较中,Patr - DRB10702和HLA - DRB10701等位基因是最相似的序列,在246个测序核苷酸中仅相差两个。在我们的黑猩猩样本中未发现与HLA - DRB101、- DRB104和- DRB109等位基因相对应的序列。对Patr - DRB等位基因数量与HLA - DRB等位基因数量进行逐个基因座比较表明,到目前为止,Patr - DRB3、- DRB4、- DRB5和- DRB6基因座比它们的人类同源基因座具有更多的多态性。Patr - DRB1基因座的多态性似乎不如报道的HLA - DRB1基因座广泛。然而,Patr - DRB1基因座似乎是Patr - DRB基因座中多态性最高的。系统发育分析表明,HLA - DRB1*09等位基因可能起源于Mhc - DRB5等位基因与Mhc - DR7单倍型的DRB1等位基因之间的重组。虽然重组似乎增加了Patr - DRB等位基因的多样性,但其对Patr - DRB变异产生的贡献可能较低。因此,大多数Patr - DRB多样性可能是通过反复的点突变积累的。最后,推断出两种不同的Patr - DRB单倍型,其中一种(相当于人类HLA - DR7单倍型的黑猩猩单倍型)可能有600 - 800万年的历史。