Origin and evolution of the adaptive immune system: genetic events and selective pressures

Abstract

The adaptive immune system as defined in humans — which includes antigen receptors generated by recombination-activating gene (RAG)-mediated rearrangement and diversified by members of the AID-APOBEC family; the major histocompatibility (MHC); extensive chemokine and cytokine networks; and secondary lymphoid tissues — arose early in the evolution of jawed vertebrates (in placoderms). The RAG transposon is believed to have invaded an immunoglobulin superfamily exon in early jawed vertebrates. It is thought to have provided a new mechanism for generating antigen receptor diversity and led to the emergence of adaptive immunity. Some features of adaptive immunity are evolutionarily conserved across species and other features show great plasticity, the latter driven by pathogens. Two rounds of whole-genome duplication produced many paralogues (ohnologues) that are essential for the adaptive immune system of jawed vertebrates. Jawless vertebrates have developed an adaptive immune system that employs variable lymphocyte receptors instead of T cell and B cell receptors. Two types of variable lymphocyte receptors — VLRA and VLRB — are expressed on T- and B-like lymphoid cells, respectively, which suggests that the origin of cell-mediated and humoral immunity predates the origin of jawed vertebrates.