An ancient evolutionary origin of the Rag1 / 2 gene locus
Open accessAbstract
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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A Rag1/2-like gene cluster was identified in the sea urchin immune gene analysis.
“One of the more unexpected findings from our analysis of sea urchin immune genes was the identification of a Rag1/2-like gene cluster (36).”
From The Genome of the Sea Urchin <i>Strongylocentrotus purpuratus</i> (2006) · cites this paper as [36]
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The Genome of the Sea Urchin <i>Strongylocentrotus purpuratus</i>
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- Authors
- Fugmann, S. D., Messier, C., Novack, L. A., Cameron, R. A., & Rast, J. P.
- Affiliations
- National Institute on Aging (US)
- University of Toronto (CA)
- California Institute of Technology (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-02-27
- Volume
- 103
- Issue
- 10
- Pages
- 3728-3733
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2007984480
- Cited by
- 177
- References
- 35
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 9 · 2020: 14 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 15 · 2015: 10 · 2014: 10 · 2013: 11 · 2012: 7
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Keywords
- RAG1, RAG2, V(D)J recombination, adaptive immunity evolution, Strongylocentrotus purpuratus, sea urchins, horizontal gene transfer, jawed vertebrates, gene co-option, antigen receptor diversity
- MeSH terms
- Amino Acid Sequence, Animals, DNA-Binding Proteins, Multigene Family, Genetic Linkage, Molecular Sequence Data, Recombinant Fusion Proteins, Gene Expression, Genes, RAG-1, Sequence Homology, Amino Acid, Homeodomain Proteins, Evolution, Molecular, Strongylocentrotus purpuratus, Mice
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