Impact of RAG transposon co-option on the evolution of the jawed vertebrate immune system

This article overviews the state of the art in comparative immunology and presents updated hypotheses on how the immune system of jawed vertebrates evolved. The main focus is on the co-option of the RAG transposon and its role in the origin of the V(D)J recombination system. This co-option is proposed to have occurred in two major stages. In the first stage, the RAG transposon, together with other eukaryote-specific transposon families such as HAT, interacted with host genes in early eukaryotic ancestors, leading to the development of a new transposition mechanism. In the second stage, RAG and host genes were specifically incorporated into the V(D)J recombination system, representing a major evolutionary innovation in jawed vertebrates. The wider impact of this event on immune system evolution is then examined. First, briefly summarize earlier hypothesis proposing that the establishment of the V(D)J recombination system contributed to the development of MHC polymorphism. Second, phylogenomic evidence indicates that key immune components of jawed vertebrates, 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. The resulting proteins interact with other immune molecules to regulate immune responses. Some proteins retained their original functions, while others acquired new functions 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.