Phylogenetic diversification of immunoglobulin genes and the antibody repertoire.
Phylogenetic diversification of immunoglobulin genes and the antibody repertoire.
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DOI：
10.1093/oxfordjournals.molbev.a040000
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发表时间：
1993
影响因子：
10.7
通讯作者：
G. Litman;J. Rast;M. Shamblott;R. Haire;M. Hulst;W. Roess;R. Litman;K. R. Hinds-Frey;Anna Zilch;Chris T. Amemiya
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文献类型：
--
作者：
G. Litman;J. Rast;M. Shamblott;R. Haire;M. Hulst;W. Roess;R. Litman;K. R. Hinds-Frey;Anna Zilch;Chris T. Amemiya
免疫球蛋白是由一个大的多基因系统编码的，该系统在产生免疫球蛋白的细胞发育期间经历体细胞重排和额外的遗传变化。诱导性抗体和抗体样反应存在于所有脊椎动物中。然而，具有二硫键键重链和轻链以及结构域型组织的免疫球蛋白仅在有颌脊椎动物的代表中描述过。高度的核苷酸和预测的氨基酸序列的同一性是显而易见的，当构成免疫球蛋白基因座的节段元件在遗传学上不同的脊椎动物进行比较。然而，基因位点的组织和独立元件重组（和多样化）的方式在不同的分类群中有显着差异。基因组织的一个引人注目的模式是“簇型”，似乎仅限于软骨鱼类（软骨鱼类），并限制了片段重排紧密相连的元素。这种类型的基因组织与重链和轻链基因位点都相关。在某些情况下，这些簇在种系中是“连接的”或“部分连接的”，实际上分别预先确定或部分预先确定各个基因座的编码特异性（假设这些特异性被表达）。通过将转录的基因产物的序列与它们各自的种系基因相关联，很明显，在某些情况下，联合型基因被表达。这就提出了一个问题，在这些物种的等位基因排斥的存在和/或性质。在整个脊椎动物物种中发现的基因组织的广泛变化可能直接与个体抗体产生细胞对特定遗传特异性的承诺中的节段间（VDJ）距离的作用有关。因此，这个基因座的进化可能比其他基因座的进化更能反映遗传组织和功能之间的相互关系。
Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (VDJ) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function.