{"doi":"10.1126/sciadv.adw1273","title":"Origin of immunoglobulins and T cell receptors: A candidate gene for invasion by the RAG transposon","abstract":"Rearranging antigen receptors (AgRs) arose when a variable (V) domain exon was invaded by the recombination-activating gene (RAG) transposon ~500 million years ago. We show here that the elasmobranch immunoglobulin heavy (IgH) isotypes—IgM, IgW, and IgNAR—are linked near the αδ T cell receptor (TCRαδ) locus. This linkage presages the emergence of the osteichthyan IgH translocon arrangement and clarifies the relationship between IgH and TCRδs. Recently, we reported UrIg , a nonrearranging, elasmobranch major histocompatibility complex (MHC)-linked AgR gene. Here, we describe a nonrearranging UrIg paralogue, UrIg2 , linked to this IgM/IgNAR/IgW/TCRαδ gene cluster in an AgR complex (AgRC). UrIg2 amino-terminal domains make homodimers where the C2-C3 structure resembles IgGFc. A relative of the UrIg2 V domain exon was invaded by the RAG transposon, revealing the genesis of the adaptive immune system. Our data indicate that an ancestral chromosome encoded an AgR precursor, undergoing RAG-mediated rearrangement after genome-wide duplication on one chromosome and retaining nonrearranging relics in the MHC and AgRC.","journal":"Science Advances","year":2025,"id":521571,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.949,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":459198,"name":"Robyn L. Stanfield","orcid":"0000-0001-9521-9184","position":1,"is_corresponding":false},{"id":445834,"name":"Ana Veríssimo","orcid":"0000-0003-3396-9822","position":2,"is_corresponding":false},{"id":992570,"name":"Harold R. Neely","orcid":"0000-0002-9886-8419","position":3,"is_corresponding":false},{"id":445829,"name":"Antonio Muñoz‐Mérida","orcid":"0000-0001-7173-2741","position":4,"is_corresponding":false},{"id":747188,"name":"Michael F. Criscitiello","orcid":"0000-0003-4262-7832","position":5,"is_corresponding":false},{"id":105430,"name":"Ian A. Wilson","orcid":"0000-0002-6469-2419","position":6,"is_corresponding":false},{"id":446542,"name":"Yuko Ohta","orcid":null,"position":7,"is_corresponding":false},{"id":445832,"name":"Martin F. Flajnik","orcid":"0000-0002-2792-5084","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40614193","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}