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

Key Points 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. How did the intricate adaptive immune system of mammals arise? New clues have recently emerged from studies of the immune systems of non-mammalian vertebrates. Here, these findings are integrated with current knowledge of macroevolutionary events and selective pressures. The adaptive immune system (AIS) in mammals, which is centred on lymphocytes bearing antigen receptors that are generated by somatic recombination, arose approximately 500 million years ago in jawed fish. This intricate defence system consists of many molecules, mechanisms and tissues that are not present in jawless vertebrates. Two macroevolutionary events are believed to have contributed to the genesis of the AIS: the emergence of the recombination-activating gene (RAG) transposon, and two rounds of whole-genome duplication. It has recently been discovered that a non-RAG-based AIS with similarities to the jawed vertebrate AIS — including two lymphoid cell lineages — arose in jawless fish by convergent evolution. We offer insights into the latest advances in this field and speculate on the selective pressures that led to the emergence and maintenance of the AIS.