人类抗体重排机制的起源

 重组激活基因（RAG）蛋白介导的抗体重排是脊椎动物适应性免疫系统的核心,抗体重排机制的起源一直是免疫学研究的热点。本研究以有活化石之称的文昌鱼为对象,对多个文昌鱼基因组草图进行深度信息学分析,发现了一个全新DNA转座子ProtoRAG。进一步功能研究表明,ProtoRAG编码的蛋白能够介导自身的转座和宿主DNA的重排,其作用机制与人类抗体蛋白介导的抗体重排机制基本一致。因此,ProtoRAG就是研究人员长期搜寻的祖先RAG转座子的“分子活化石”,该发现为诺贝尔生理学或医学奖获得者利根川进提出的“抗体重排机制转座子起源”假说提供了最有力和最直接的证据。

The origin of human V(D)J recombination mechanism

Vertebrate V(D)J recombination is mediated by RAG proteins and plays a core role in the vertebrate adaptive immune system. Thus, the origin of V(D)J recombination mechanism has always been a hot spot of immunology research. In this study, amphioxus is chosen as the model species, which is called "living fossil" of vertebrate ancestor. Based on in-depth bioinformatics analyses of three amphioxus genomes and systematic functional research, the ProtoRAG transposon encoding RAG homologous proteins is found. Functional experiments show that ProtoRAG is an active transposon encoding original RAG1/2-like protein, which not only mediates the transfer of itself but also catalyzes the V(D)J rearrangement in a way similar to RAGs in vertebrates. Thus, ProtoRAG represents a molecular "living fossil" of the long-sought ancestral RAG transposon. These findings provide direct and compelling evidence that V(D)J recombination evolved subsequent to an ancestral transposon, as proposed by Tonegawa in 1979. The results of this study are published in Cell in June 2016 and were considered to be evidence of G.O.D.'s (Generation Of Diversity) miracle.