Origin of immunoglobulins and T cell receptors: A candidate gene for invasion by the RAG transposon
- Martin F. Flajnik
- Robyn L. Stanfield
- Ana Verissimo
- Harold R. Neely
- Antonio Muñoz-Mérida
- Michael F. Criscitiello
- Ian A. Wilson
- Yuko Ohta
2025-07-04
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.