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.

V (D) J recombination  /  RAG  /  amphioxus  /  ProtoRAG transposon