ArticleNature2019
Transposon molecular domestication and the evolution of the RAG recombinase.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.Frontiers in immunology · 2021Pooled it
- Thymic APC Networks Orchestrate T-Cell Selection: Mechanisms and Therapeutic Opportunities in Immune Disorders.Immunology · 2026Review
- A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multiple evolutionary routes to immune diversification across animals.International immunology · 2026Review
- Discontinuous genomic coding and paradigm shifts in molecular biology and immunology: revolutions via "normal science".Natural sciences (Weinheim, Germany) · 2026Article
- Class switched bovine ultralong CDR H3 amplicons versus canonical in immune and non-immune tissues.Immunogenetics · 2026Article
- Imagin: An Integrase-Like Gene Conserved Across Malacostracan Crustaceans Derived From a Ginger1 DNA Transposon.Genome biology and evolution · 2026Article
- Proximity-based proteomic profiling uncovers distinct interactome of human RAG1 and RAG2.Acta biochimica et biophysica Sinica · 2026Article
- How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ThebioRxiv : the preprint server for biology · 2025Article
- The Quest for Antibodies and Other Acquired Immune Receptors: A Historical Perspective.International journal of immunogenetics · 2025Review
- RAG suppresses group 2 innate lymphoid cells.eLife · 2025Article
- The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms.Immunological reviews · 2024Review
- Evolutionary preservation of CpG dinucleotides in RAG1 may elucidate the relatively high rate of methylation-mediated mutagenesis of RAG1 transposase.Immunologic research · 2024Article
- Strain-specific evolution and host-specific regulation of transposable elements in the model plant symbiont Rhizophagus irregularis.G3 (Bethesda, Md.) · 2024Article
- Recent reactivation of a pathogenicity-associated transposable element is associated with major chromosomal rearrangements in a fungal wheat pathogen.Nucleic acids research · 2024Article
- DNA on the move: mechanisms, functions and applications of transposable elements.FEBS open bio · 2024Review
- Insights into RAG Evolution from the Identification of "Missing Link" Family A RAGL Transposons.Molecular biology and evolution · 2023Article
- A History and Atlas of the Human CD4Biomedicines · 2023Review
- Chiropterans Are a Hotspot for Horizontal Transfer of DNA Transposons in Mammalia.Molecular biology and evolution · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Domestication of a transposon (a DNA sequence that can change its position in a genome) to give rise to the RAG1-RAG2 recombinase (RAG) and V(D)J recombination, which produces the diverse repertoire of antibodies and T cell receptors, was a pivotal event in the evolution of the adaptive immune system of jawed vertebrates. The evolutionary adaptations that transformed the ancestral RAG transposase into a RAG recombinase with appropriately regulated DNA cleavage and transposition activities are not understood. Here, beginning with cryo-electron microscopy structures of the amphioxus ProtoRAG transposase (an evolutionary relative of RAG), we identify amino acid residues and domains the acquisition or loss of which underpins the propensity of RAG for coupled cleavage, its preference for asymmetric DNA substrates and its inability to perform transposition in cells. In particular, we identify two adaptations specific to jawed-vertebrates-arginine 848 in RAG1 and an acidic region in RAG2-that together suppress RAG-mediated transposition more than 1,000-fold. Our findings reveal a two-tiered mechanism for the suppression of RAG-mediated transposition, illuminate the evolution of V(D)J recombination and provide insight into the principles that govern the molecular domestication of transposons.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.