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

Author

Listed:
  • Alka Agrawal

    (Department of Pharmacology)

  • Quinn M. Eastman

    (Department of Molecular Biophysics and Biochemistry)

  • David G. Schatz

    (Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine)

Abstract

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.

Suggested Citation

  • Alka Agrawal & Quinn M. Eastman & David G. Schatz, 1998. "Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system," Nature, Nature, vol. 394(6695), pages 744-751, August.
    • Handle: RePEc:nat:nature:v:394:y:1998:i:6695:d:10.1038_29457
    DOI: 10.1038/29457
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    Cited by:

    1. Yingyi Huang & Xiang Liu & Shuo Li & Chen Li & Hong-Yan Wang & Qun Liu & Jian-Yang Chen & Yingying Zhang & Yanan Li & Xianghui Zhang & Qian Wang & Kaiqiang Liu & Yu-Yan Liu & Yue Pang & Shanshan Liu &, 2024. "Discovery of an unconventional lamprey lymphocyte lineage highlights divergent features in vertebrate adaptive immune system evolution," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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