Nature 394, 744-751 (20 August 1998) | doi:10.1038/29457; Received 6 July 1998; Accepted 30 July 1998

Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system

Alka Agrawal1, Quinn M. Eastman2 & David G. Schatz3

  1. Department of Pharmacology, New Haven, Connecticut 06510, USA
  2. Department of Molecular Biophysics and Biochemistry, New Haven, Connecticut 06510 , USA
  3. Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA

Correspondence to: David G. Schatz3 Correspondence and requests for materials should be addressed to D.G.S. (e-mail: Email:


Immunoglobulin and T-cell-receptor genes are assembled from component gene segments in developing lymphocytes by a site-specific recombination reaction, V (D)J recombination. The proteins encoded by the recombination-activating genes, RAG1 and RAG2, are essential in this reaction, mediating sequence-specific DNA recognition of well-defined recombination signals and DNA cleavage next to these signals. Here we show that RAG1 and RAG2 together form a transposase capable of excising a piece of DNA containing recombination signals from a donor site and inserting it into a target DNA molecule. The products formed contain a short duplication of target DNA immediately flanking the transposed fragment, a structure like that created by retroviral integration and all known transposition reactions. The results support the theory that RAG1 and RAG2 were once components of a transposable element, and that the split nature of immunoglobulin and T-cell-receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates.