Matsuda F, Ishii K, Bourvagnet P, Kuma K i, Hayashida H, Miyata T, Honjo T
Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Kyoto 60601, Japan.
J Exp Med. 1998 Dec 7;188(11):2151-62. doi: 10.1084/jem.188.11.2151.
The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (VH) region locus was determined and 43 novel VH segments were identified. The region contains 123 VH segments classifiable into seven different families, of which 79 are pseudogenes. Of the 44 VH segments with an open reading frame, 39 are expressed as heavy chain proteins and 1 as mRNA, while the remaining 4 are not found in immunoglobulin cDNAs. Combinatorial diversity of VH region was calculated to be approximately 6,000. Conservation of the promoter and recombination signal sequences was observed to be higher in functional VH segments than in pseudogenes. Phylogenetic analysis of 114 VH segments clearly showed clustering of the VH segments of each family. However, an independent branch in the tree contained a single VH, V4-44.1P, sharing similar levels of homology to human VH families and to those of other vertebrates. Comparison between different copies of homologous units that appear repeatedly across the locus clearly demonstrates that dynamic DNA reorganization of the locus took place at least eight times between 133 and 10 million years ago. One nonimmunoglobulin gene of unknown function was identified in the intergenic region.
测定了人类免疫球蛋白重链可变（VH）区基因座957 kb DNA的完整核苷酸序列，并鉴定出43个新的VH片段。该区域包含123个VH片段，可分为七个不同的家族，其中79个是假基因。在44个具有开放阅读框的VH片段中，39个表达为重链蛋白，1个表达为mRNA，而其余4个在免疫球蛋白cDNA中未发现。VH区的组合多样性经计算约为6000。观察到功能性VH片段中启动子和重组信号序列的保守性高于假基因。对114个VH片段的系统发育分析清楚地显示了每个家族的VH片段聚类。然而，树中的一个独立分支包含一个单一的VH，V4 - 44.1P，它与人类VH家族以及其他脊椎动物的VH家族具有相似的同源水平。对在整个基因座中反复出现的同源单位的不同拷贝进行比较，清楚地表明该基因座的动态DNA重组在1.33亿至1000万年前至少发生了八次。在基因间区域鉴定出一个功能未知的非免疫球蛋白基因。
