ArticleProceedings of the National Academy of Sciences of the United States of America2014
An amphioxus RAG1-like DNA fragment encodes a functional central domain of vertebrate core RAG1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 38 citations in OpenAlex.
- Multiple evolutionary routes to immune diversification across animals.International immunology · 2026Review
- Insights into cephalochordate genome and gene evolution from the early-diverging amphioxusProceedings of the National Academy of Sciences of the United States of America · 2026Article
- On the relationship between extant innate immune receptors and the evolutionary origins of jawed vertebrate adaptive immunity.Immunogenetics · 2022Review
- 'Cannibalism' of exogenous DNA sequences: The ancestral form of adaptive immunity which entails recognition of danger.Frontiers in immunology · 2022Review
- On Origin and Evolution of the Antibody Molecule.Biology · 2021Review
- Identification and Characterization of the Amphioxus Lck and Its Associated Tyrosine Phosphorylation-Dependent Inhibitory LRR Receptor.Frontiers in immunology · 2021Article
- Co-evolution of mutagenic genome editors and vertebrate adaptive immunity.Current opinion in immunology · 2020Review
- Functional requirement of terminal inverted repeats for efficientNational science review · 2020Article
- New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.The FEBS journal · 2017Review
- Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.Trends in biochemical sciences · 2017Review
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- Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination.Genes & development · 2016Article
- Was the evolutionary road towards adaptive immunity paved with endothelium?Biology direct · 2015Article
- The cell survival pathways of the primordial RNA-DNA complex remain conserved in the extant genomes and may function as proto-oncogenes.European journal of microbiology & immunology · 2015Review
- RAG1-mediated ubiquitylation of histone H3 is required for chromosomal V(D)J recombination.Cell research · 2015Article
- Commentary on: "A common origin for immunity and digestion".Frontiers in microbiology · 2015Article
- Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes.Nature communications · 2014Article
- Evolution of Innate Immunity: Clues from Invertebrates via Fish to Mammals.Frontiers in immunology · 2014Review
- Review
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The highly diversified repertoire of antigen receptors in the vertebrate immune system is generated via proteins encoded by the recombination activating genes (RAGs) RAG1 and RAG2 by a process known as variable, diversity, and joining [V(D)J] gene recombination. Based on the study of vertebrate RAG proteins, many hypotheses have been proposed regarding the origin and evolution of RAG. This issue remains unresolved, leaving a significant gap in our understanding of the evolution of adaptive immunity. Here, we show that the amphioxus genome contains an ancient RAG1-like DNA fragment (bfRAG1L) that encodes a virus-related protein that is much shorter than vertebrate RAG1 and harbors a region homologous to the central domain of core RAG1 (cRAG1). bfRAG1L also contains an unexpected retroviral type II nuclease active site motif, DXN(D/E)XK, and is capable of degrading both DNA and RNA. Moreover, bfRAG1L shares important functional properties with the central domain of cRAG1, including interaction with RAG2 and localization to the nucleus. Remarkably, the reconstitution of bfRAG1L into a cRAG1-like protein yielded an enzyme capable of recognizing recombination signal sequences and performing V(D)J recombination in the presence of mouse RAG2. Moreover, this reconstituted cRAG1-like protein could mediate the assembly of antigen receptor genes in RAG1-deficient mice. Together, our results demonstrate that amphioxus bfRAG1L encodes a protein that is functionally equivalent to the central domain of cRAG1 and is well prepared for further evolution to mediate V(D)J recombination. Thus, our findings provide unique insights into the evolutionary origin of RAG1.
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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.