>500 Million years ago
||Litman GW, Cannon JP, Dishaw LJ. Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol. 2005 Nov5(11):866-79 DOI: 10.1038/nri1712 p.866 left column bottom paragraphPubMed ID16261174
|| Agrawal A, Eastman QM, Schatz DG. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature. 1998 Aug 20 394(6695):744-51 DOI: 10.1038/29457  Hiom K, Melek M, Gellert M. DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations. Cell. 1998 Aug 21 94(4):463-70PubMed ID9723614, 9727489
||P.866 left column bottom paragraph: "More than 500 million years ago, a TRANSPOSITION event, probably involving a recombination-activating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity (primary sources), which has evolved to create a mechanism for deriving almost limitless variation from very few genes."