Origins of the RAG Transposome and the MHC. Issue 7 (July 2020)

• Record Type: Journal Article
• Authors: Tsakou-Ngouafo, Louis; Paganini, Julien; Kaufman, Jim; Pontarotti, Pierre
• Is Part Of: Trends in immunology. Volume 41:Issue 7(2020)
• Page Start: 561
• Page End: 571
• Publication Date: 2020-07
• Subjects: hairpin -- flanking -- DDE transposon excision -- Artemis -- palindromic diversity -- convergent evolution; Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2020.05.002
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular pattern(s) (PAMPs) being presented by molecule(s) on one cell to specific receptor(s) on other cells, much like MHC molecules and T cell receptors (TCRs). In this model, mutations in MHC-like molecule(s) that bound new PAMP(s) would not be recognized by original TCR-like molecule(s), and new MHC-like gene(s) would be lost by neutral drift. Integrating recombination activating gene (RAG) transposon(s) in a TCR-like gene would result in greater recognition diversity, with new MHC-like variants recognized and selected, along with a new RAG/TCR-like system. MHC genes would be selected to present many peptides, through multigene families, allelic polymorphism, and peptide-binding promiscuity. Highlights: RAG evolved from a DDE transposon present in the ancestor of bilaterian animals; it evolved in a vertical manner and was domesticated as RAG in a jawed vertebrate ancestor. This RAG-like transposon belonged to a transposon family with an ability to create palindromic (P) diversity. A proposed model is that the jawed vertebrate ancestor possessed a complex and powerful innate immune system, where the pre-MHC molecule was able to bind and present certain PAMP molecules to a monomorphic, non-rearranging TCR-like molecule. The integration of the RAG transposon in the recognition module of the TCR-like gene may have led to a significant increase in recognition possibilities, presumably allowing new MHC-like variants to be selected. Hypothetically, the increase in recognition possibilities may have also led to the appearance of MHC polymorphisms and an increase in peptide-binding repertoires (promiscuity).