Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
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.
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RAG1/2-mediated transpositions also show significant target specificity, presumably reflecting the original specificity of the Transib TPase.
“RAG1/2-mediated transpositions also show significant target specificity, presumably reflecting the original specificity of the Transib TPase [12].”
From RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons (2005) · cites this paper as [12]
RAG1-mediated transposition in vitro, both intermolecular and intramolecular, is most frequently accompanied by 5-bp TSDs.
“It has been known that RAG1-mediated transposition in vitro, both intermolecular and intramolecular, is most frequently accompanied by 5-bp TSDs [12,13].”
From RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons (2005) · cites this paper as [12]
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- Authors
- Agrawal, A., Eastman, Q. M., & Schatz, D. G.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Schatz, David G.
- ORCID
- Schatz, David G.
- Venue
- Nature
- Published
- 1998-08
- Volume
- 394
- Issue
- 6695
- Pages
- 744-751
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1513093379
- Cited by
- 811
- References
- 44
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 19 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 27 · 2019: 18 · 2018: 12 · 2017: 11 · 2016: 17 · 2015: 24 · 2014: 18 · 2013: 16 · 2012: 37
- FWCI
- 20.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- RAG1, RAG2, V(D)J recombination, transposition, transposase, immunoglobulin genes, T cell receptor genes, transposable elements, immune system evolution, jawless fishes
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, B-Lymphocytes, Binding Sites, Catalysis, Cell Line, DNA, DNA Transposable Elements, DNA-Binding Proteins, DNA, Circular, Drug Resistance, Microbial, High Mobility Group Proteins, Immune System, Molecular Sequence Data, Receptors, Antigen, T-Cell, Recombination, Genetic, Vertebrates, Restriction Mapping, Gene Rearrangement, B-Lymphocyte, Gene Rearrangement, T-Lymphocyte, Homeodomain Proteins, Evolution, Molecular, Transposases, Mice
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