TRANSPOSITION MEDIATED BY RAG1 AND RAG2 AND ITS IMPLICATIONS FOR THE EVOLUTION OF THE IMMUNE-SYSTEM

Immunoglobulin and T-cell-receptor genes are assembled from component gene segments in developing lymphocytes by a site-specific recombinati on reaction, V(D)J recombination, The proteins encoded by the recombin ation-activating genes, RAG1 and RAG2, are essential in this reaction, mediating sequence-specific DNA recognition of well-defined recombina tion signals and DNA cleavage next to these signals. Here we show that RAG1 and RAG2 together form a transposase capable of excising a piece of DNA containing recombination signals from a donor site and inserti ng it into a target DNA molecule. The products formed contain a short duplication of target DNA Immediately flanking the transposed fragment , a structure like that created by retroviral integration and all know n transposition reactions. The results support the theory that RAG1 an d RAG2 were once components of a transposable element, and that the sp lit nature of Immunoglobulin and T-cell-receptor genes derives from ge rmline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates.