Phylogenetic analyses of the HLA-DRB1 gene based on the DR haplotypes

人类白细胞抗原（human leukocyte antigen，HLA）-DRB 1基因是人类基因组中具有高度多态性的基因，具有大量的等位基因，包括DRB 1在内的DR亚区也具有与活性DRB基因及其假基因的基因组结构多态性。DRB 1等位基因的分类是研究DRB 1等位基因遗传学的一个重要参数。使用DRB 1等位基因的核苷酸序列，通过相邻连接和UPGMA方法构建的HLA-DRB 1等位基因的传统系统发育树表明，DRB 1 ^*0701可能在人类和黑猩猩物种分离之前就与其他DRB 1等位基因发生了分化，因为与其他DRB 1等位基因相比，DRB 1 ^*0701的核苷酸发生了大量变化。在本研究中，我们发现了以DRB 1 ^*0701和DRB 1 ^*04等位基因为中心的单倍型最同源的新证据。这表明，这些单倍型来自共同祖先单倍型， 关于我们 型，并且即使在DRB 1 ^*0701和DRB 1 ^*04等位基因谱系分化之后，它们也可能保留了完整的连锁不平衡。连同携带与HLA-DRB 1 ^* 0701具有高度序列同源性的黑猩猩DRB 1 ^*0701的相应单倍型，这些单倍型揭示了：i）DRB 1 ^*04等位基因谱系可能是在人类和黑猩猩物种分离后从DRB 1 ^*0701谱系产生的，ii）DRB 1 ^*04等位基因谱系与假基因和中性区相比可能具有更高的DRB 1置换率，DRB 1 ^*0701和DRB 1 ^*04等位基因谱系之间DRB 1的替换率可能存在显著差异。基于目前与以往结果的差异，我们建议，系统发育研究不仅使用的DRB 1等位基因的核苷酸序列，但也以等位基因为中心的单倍型应该进行详细的DRB 1等位基因的系统发育关系的理解。少

The human leukocyte antigen (HLA)-DRB1 is a highly polymorphic gene with a large number of alleles in the human genome, and the DR subregion including DRB1 also possesses polymorphism in terms of its genome organization with active DRB genes and their pseudogenes. Classification of DRB1 alleles based on the DR groups seems to be an important parameter for studying the phylogeny of the DRB1 alleles. Conventional phylogenetic trees for the HLA-DRB1 alleles constructed by the neighbor-joining and UPGMA methods using nucleotide sequences of the DRB1 alleles suggest that DRB1^*0701 may have diverged from other DRB1 alleles before the separation of the human and chimpanzee species because of a large number of nucleotide changes in DRB1^*0701 compared with any of the other DRB1 alleles. In this study we show the new evidence that the haplotypes centering on DRB1^*0701 and DRB1^*04 alleles are the most homologous. This suggests that these haplotypes have derived from the common-ancestral haplo … More type, and that they have likely retained the complete linkage disequilibrium even after the divergence of the DRB1^*0701 and DRB1^*04 allelic lineages. Together with the corresponding haplotype carrying chimpanzee DRB1^*0701 which has a high sequence homology to HLA-DRB1^*0701,these haplotypes reveal that : i)the DRB1^*04 allelic lineage may have been generated from the DRB1^*0701 lineage after the separation of the human and chimpanzee species, ii)the DRB1^*04 allelic lineage has possibly higher substitution rate of DRB1 compared with pseudogene and neutral region, and iii)there could be a significant difference in the substitution rate of DRB1 between the DRB1^*0701 and DRB1^*04 allelic lineages. Based on the difference between the present and previous results, we would like to propose that phylogenetic studies using not only nucleotide sequences of the DRB1 alleles but also haplotypes centering on the alleles should be conducted for understanding detailed phylogenetic relationships of the DRB1 alleles. Less