Evidence of G.O.D.'s Miracle: Unearthing a RAG Transposon

Abstract

Diversity of antibodies and T cell receptors is generated by gene rearrangement dependent on RAG1 and RAG2, enzymes predicted to have been derived from a transposable element (TE) that invaded an immunoglobulin superfamily gene early in the evolution of jawed vertebrates. Now, Huang et al. report the discovery of ProtoRAG in the lower chordate Amphioxus, the long-anticipated TE related to the RAG transposon.

Figure 1. Historical Events Culminating in the Discovery of ProtoRag in Amphioxus

The discoveries of RSS (by Tonegawa and colleagues), the RAG proteins (by Baltimore and colleagues), and the mechanism of RSS cleavage (by Oettinger/Gellert and colleagues) resulted in the theory that a TE invaded an IgSF gene, eventually leading to Ig/TCR gene rearrangement (by Thompson). Experiments showing that the RAGs are capable of DNA transposition (by Schatz/Gellert and colleagues), the presence of RAG in all gnathostomes (by Marchalonis and colleagues), and the presence of a RAG1 core and TIR in the invertebrates (by Kaptinov and Jurka) were consistent with the model. Discovery of linked RAG1L and RAG2L in lower deuterostomes (by Fugmann/Rast and colleagues), including a complete and active RAG transposon in Amphioxus (Huang et al., 2016), are consistent with the hypothesis.