Impact of RAG Transposon Co-Option on the Evolution of the Jawed Vertebrate Immune System

This article reviews current knowledge in comparative immunology and presents updated hypotheses on the evolution of the immune system in jawed vertebrates. It focuses on the co-option of the RAG transposon in the origin of the V(D)J recombination system, proposed to have occurred in two stages. Initially, the RAG transposon, along with other eukaryote-specific transposon such as HAT, interacted with host genes in early eukaryotes, leading to a new transposition mechanism. Subsequently, RAG and host genes were integrated into the V(D)J recombination system, representing a major evolutionary innovation. The broader implications of this events are also considered. Earlier hypothesis suggest that the establishment of the V(D)J recombination system contributed to MHC polymorphism. Phylogenomic evidence indicates that key immune components, including MHC, T-cell receptors (α,β and γ,δ), and immunoglobulins, existed in ancestors and later expanded through gene duplication, forming multigene families with diverse functions. Their proteins products interact with other immune molecules to regulate immune responses. While some retained original functions, others evolved new roles through neo-functionalization. Overall, the co-option of the RAG transposon played a critical role in shaping the immune system of jawed vertebrates by driving innovation in both adaptive and innate immunity.