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Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination #MMPMID27293192
Huang S; Tao X; Yuan S; Zhang Y; Li P; Beilinson HA; Zhang Y; Yu W; Pontarotti P; Escriva H; Le Petillon Y; Liu X; Chen S; Schatz DG; Xu A
Cell 2016[Jun]; 166 (1): 102-14 PMID27293192show ga
Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5 bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences. Between the TIRs reside tail-to-tail oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germline and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular ?living fossil? of the long-sought RAG transposon.