Hsu Ellen, Pulham Nicolas, Rumfelt Lynn L, Flajnik Martin F
Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.
Immunol Rev. 2006 Apr;210:8-26. doi: 10.1111/j.0105-2896.2006.00366.x.
The mechanism of recombination-activating gene (RAG)-mediated rearrangement exists in all jawed vertebrates, but the organization and structure of immunoglobulin (Ig) genes, as they differ in fish and among fish species, reveal their capability for rapid evolution. In systems where there can exist 100 Ig loci, exon restructuring and sequence changes of the constant regions led to divergence of effector functions. Recombination among these loci created hybrid genes, the strangest of which encode variable (V) regions that function as part of secreted molecules and, as the result of an ancient translocation, are also grafted onto the T-cell receptor. Genomic changes in V-gene structure, created by RAG recombinase acting on germline recombination signal sequences, led variously to the generation of fixed receptor specificities, pseudogene templates for gene conversion, and ultimately to Ig sequences that evolved away from Ig function. The presence of so many Ig loci in fishes raises interesting questions not only as to how their regulation is achieved but also how successive whole-locus duplications are accommodated by a system whose function in other vertebrates is based on clonal antigen receptor expression.
重组激活基因（RAG）介导的重排机制存在于所有有颌脊椎动物中，但免疫球蛋白（Ig）基因的组织和结构在鱼类及不同鱼类物种之间存在差异，这揭示了它们快速进化的能力。在可能存在100个Ig基因座的系统中，恒定区的外显子重组和序列变化导致效应功能的分化。这些基因座之间的重组产生了杂交基因，其中最奇特的是编码可变（V）区的基因，这些可变区作为分泌分子的一部分发挥作用，并且由于一次古老的易位，也被嫁接到T细胞受体上。RAG重组酶作用于种系重组信号序列所产生的V基因结构的基因组变化，以各种方式导致了固定受体特异性的产生、用于基因转换的假基因模板的形成，最终导致Ig序列从Ig功能中分化出来。鱼类中存在如此多的Ig基因座，这不仅引发了关于它们如何实现调控的有趣问题，还引发了关于一个在其他脊椎动物中其功能基于克隆抗原受体表达的系统如何容纳连续的全基因座重复的问题。
