Svensson A C, Setterblad N, Sigurdardóttir S, Rask L, Andersson G
Uppsala Genetic Center, Department of Cell Research, Swedish University of Agricultural Sciences.
Immunogenetics. 1995;41(2-3):74-82. doi: 10.1007/BF00182316.
The HLA-DRB genes of the human major histocompatibility complex constitute a multigene family with a varying number of DRB genes in different haplotypes. To gain further knowledge concerning the evolutionary relationship, the complete nucleotide sequence was determined for a region spanning introns 4 and 5 of the three DRB genes (DRB10301, DRB2, and DRB30101) from a DR52 haplotype and the single DRB gene (DRB108021) in the DR8 haplotype. These analyses identified as endogenous retroviral long terminal repeat element (ERV9 LTR3), inserted at identical positions in intron 5 of the functional DRB genes in these two haplotypes. Comparison of the nucleotide sequence from introns 4 and 5 including the ERV9 LTR elements revealed a strong similarity between the three expressed DRB genes. The DRB30101 and DRB1*08021 genes were most similar in this comparison. These findings provide further evidence for a separate duplication in a primordial DR52 haplotype followed by a gene contraction event in the DR8 haplotype. A homologous element was found in a chimpanzee DRB gene from a DR52 haplotype. This represents the first characterized ERV9 LTR element in a nonhuman species. The corresponding introns of the DRB genes in the DR4 haplotype contain no ERV9 LTRs. In contrast, these genes have insertions of distinct Alu repeats, implying distinct evolutionary histories of DR52 and DR53 haplotypes, respectively. Phylogenetic analyses of DRB introns from DR52, DR53, and DR8 haplotypes showed a close relationship between the DRB2 and DRB4 genes. Thus, the ancestral DR haplotype that evolved to generate the DR52 and DR53 haplotypes most likely shared a primordial common DRB gene.
人类主要组织相容性复合体的HLA - DRB基因构成了一个多基因家族，不同单倍型中DRB基因的数量各不相同。为了进一步了解其进化关系，测定了来自DR52单倍型的三个DRB基因（DRB10301、DRB2和DRB30101）以及DR8单倍型中的单个DRB基因（DRB108021）跨越内含子4和5区域的完整核苷酸序列。这些分析确定了一个内源性逆转录病毒长末端重复元件（ERV9 LTR3），它插入在这两个单倍型中功能性DRB基因的内含子5的相同位置。对包括ERV9 LTR元件在内的内含子4和5的核苷酸序列进行比较，发现三个表达的DRB基因之间有很强的相似性。在这次比较中，DRB30101和DRB1*08021基因最为相似。这些发现为原始DR52单倍型中的一次单独复制提供了进一步证据，随后DR8单倍型中发生了基因收缩事件。在来自DR52单倍型的黑猩猩DRB基因中发现了一个同源元件。这代表了非人类物种中第一个被表征的ERV9 LTR元件。DR4单倍型中DRB基因的相应内含子不包含ERV9 LTR。相反，这些基因有不同的Alu重复序列插入，这分别意味着DR52和DR53单倍型有不同的进化历史。对DR52、DR53和DR8单倍型的DRB内含子进行系统发育分析，结果显示DRB2和DRB4基因关系密切。因此，进化产生DR52和DR53单倍型的祖先DR单倍型很可能共享一个原始的共同DRB基因。
