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

Nature. 1998 Aug 20;394(6695):744-51. doi: 10.1038/29457.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / genetics
  • B-Lymphocytes / physiology
  • Binding Sites
  • Catalysis
  • Cell Line
  • DNA / metabolism
  • DNA Transposable Elements*
  • DNA, Circular / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Drug Resistance, Microbial / genetics
  • Evolution, Molecular*
  • Gene Rearrangement, B-Lymphocyte*
  • Gene Rearrangement, T-Lymphocyte*
  • High Mobility Group Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Immune System / physiology*
  • Mice
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / genetics
  • Recombination, Genetic
  • Restriction Mapping
  • Transposases / metabolism
  • Vertebrates / genetics
  • Vertebrates / immunology

Substances

  • Antibodies
  • DNA Transposable Elements
  • DNA, Circular
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • DNA
  • Transposases