The Origin of V(D)J Diversification

The vertebrate immune system can respond to an ever-changing spectrum of pathogens, and V(D)J recombination plays a central role in achieving this stunning versatility. V(D)J recombination first appeared in vertebrates about 450. million years ago and seemingly emerged without antecedent in evolution, an observation suggesting that the essentials of the recombination machinery were acquired through horizontal transfer and subsequent exaptation. This chapter examines the idea that the very apparatus is derived from part of a DNA transposon by comparing the biochemistry of transposases and the RAG recombinase. We hypothesize that the recombinase not only functions in lymphocytes but has since its acquisition also acted on germ cell genomic sequence, thereby influencing the structure and organization of immunoglobulin and T cell receptor loci. Lastly, we consider the nature of the immune system in the ancestral vertebrate, prior to the development of V(D)J recombination, and review current thinking on how V(D)J recombination fits into the evolution of adaptive immunity as a whole.