Gongora R, Figueroa F, Klein J
Max-Planck-Institut für Biologie, Abteilung Immungenetik, Tübingen, Germany.
Hum Immunol. 1996 Nov;51(1):23-31. doi: 10.1016/s0198-8859(96)00189-9.
HLA-DRB9 is a gene fragment consisting of exon 2 and flanking intron sequences. It is located at the extreme end of the DRB subregion, whose other end is demarcated by the DRB1 locus. We sequenced approximately 1400 base pairs of the segment encompassing the DRB9 locus from eight human haplotypes (DR1, DR10, DR2, DR3, DR5, DR6, DR8, and DR9, the DR4 and DR7 having been sequenced by others earlier), as well as two chimpanzee, five gorillas, one orangutan and one macaque haplotype. The analysis of these sequences indicates that the DRB9 locus, which we estimate to be more than 58 million years (my) old, has been coevolving with the DRB1 locus for the last 4.2 my. As a consequence of this coevolution, the human DRB9 alleles fall into groups that correlate with the DRB1 allelic groups and with the gene organization of the human haplotypes. This observation implies that the present-day HLA-DR haplotype groups (DR1, DR51, DR52, DR8, and DR53) were founded more than 4 my ago and have remained intact (barring minor internal rearrangements that did not recombine the DRB1 and DRB9 genes) for this period of time. The haplotypes have been transmitted during speciations from ancestral to emerging species just like allelic lineages at the DRB1 locus. Thus not only allelic but also haplotype polymorphism evolves trans-specifically.
HLA - DRB9是一个由外显子2和侧翼内含子序列组成的基因片段。它位于DRB亚区域的最末端，该区域的另一端由DRB1基因座划定。我们对来自8种人类单倍型（DR1、DR10、DR2、DR3、DR5、DR6、DR8和DR9，DR4和DR7已由其他人先前测序）以及2种黑猩猩、5种大猩猩、1种猩猩和1种猕猴单倍型的包含DRB9基因座的片段进行了约1400个碱基对的测序。对这些序列的分析表明，我们估计有超过5800万年历史的DRB9基因座在过去420万年中一直与DRB1基因座共同进化。这种共同进化的结果是，人类DRB9等位基因可分为与DRB1等位基因组以及人类单倍型的基因组织相关的组。这一观察结果意味着，当今的HLA - DR单倍型组（DR1、DR51、DR52、DR8和DR53）在400多万年前就已形成，并且在此期间一直保持完整（除了未重组DRB1和DRB9基因的微小内部重排）。这些单倍型在物种形成过程中像DRB1基因座的等位基因谱系一样从祖先物种传递到新出现的物种。因此，不仅等位基因多态性，而且单倍型多态性都是跨物种进化的。
