ArticleProceedings of the National Academy of Sciences of the United States of America2006
An ancient evolutionary origin of the Rag1/2 gene locus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 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
- Integrated Symbiotic Pleiotropy: Long Non-Coding RNAs and Disordered Proteins Interweaving the Functional Layers of the Eukaryotic Cell.International journal of molecular sciences · 2026Review
- Revisiting T cells: Innate actions and emerging links to innate memory response.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Immunity: defense against infections essential for all living organisms.Frontiers in immunology · 2026Review
- Evolutionary insights and structural characterization guide the development of RAG1/RAG2-deficient swine models for immunological research.Frontiers in immunology · 2026Article
- Structures reveal how the Cas1-2/3 integrase captures, delivers, and integrates foreign DNA into CRISPR loci.Structure (London, England : 1993) · 2025Article
- Integrated system for screening tumor-specific TCRs, epitopes, and HLA subtypes using single-cell sequencing data.Journal for immunotherapy of cancer · 2025Article
- Evolutionary preservation of CpG dinucleotides in RAG1 may elucidate the relatively high rate of methylation-mediated mutagenesis of RAG1 transposase.Immunologic research · 2024Article
- Insights into RAG Evolution from the Identification of "Missing Link" Family A RAGL Transposons.Molecular biology and evolution · 2023Article
- Structural insights into the evolution of the RAG recombinase.Nature reviews. Immunology · 2022Review
- Different sea urchin RAG-like genes were domesticated to carry out different functions.Frontiers in immunology · 2022Article
- 'Cannibalism' of exogenous DNA sequences: The ancestral form of adaptive immunity which entails recognition of danger.Frontiers in immunology · 2022Review
- The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination.The Journal of experimental medicine · 2021Article
- Review
- On Origin and Evolution of the Antibody Molecule.Biology · 2021Review
- Evolution of thymopoietic microenvironments.Open biology · 2021Review
- Guardian of the Genome: An Alternative RAG/Transib Co-Evolution Hypothesis for the Origin of V(D)J Recombination.Frontiers in immunology · 2021Article
- Co-evolution of mutagenic genome editors and vertebrate adaptive immunity.Current opinion in immunology · 2020Review
- MHC Class I Regulation: The Origin Perspective.Cancers · 2020Article
- Functional requirement of terminal inverted repeats for efficientNational science review · 2020Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
The diversity of antigen receptors in the adaptive immune system of jawed vertebrates is generated by a unique process of somatic gene rearrangement known as V(D)J recombination. The Rag1 and Rag2 proteins are the key mediators of this process. They are encoded by a compact gene cluster that has exclusively been identified in animal species displaying V(D)J-mediated immunity, and no homologous gene pair has been identified in other organisms. This distinctly restricted phylogenetic distribution has led to the hypothesis that one or both of the Rag genes were coopted after horizontal gene transfer and assembled into a Rag1/2 gene cluster in a common jawed vertebrate ancestor. Here, we identify and characterize a closely linked pair of genes, SpRag1L and SpRag2L, from an invertebrate, the purple sea urchin (Strongylocentrotus purpuratus) with similarity in both sequence and genomic organization to the vertebrate Rag1 and Rag2 genes. They are coexpressed during development and in adult tissues, and recombinant versions of the proteins form a stable complex with each other as well as with Rag1 and Rag2 proteins from several vertebrate species. We thus conclude that SpRag1L and SpRag2L represent homologs of vertebrate Rag1 and Rag2. In combination with the apparent absence of V(D)J recombination in echinoderms, this finding strongly suggests that linked Rag1- and Rag2-like genes were already present and functioning in a different capacity in the common ancestor of living deuterostomes, and that their specific role in the adaptive immune system was acquired much later in an early jawed vertebrate.
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