Figure 4. The Co-regulatory model including initial insertion of a primordial herpes virus recombinase (proto-RAG-1 denoted pR1) adjacent to a pre-existing RAG-2 like protein (denoted pR2) is shown.

As shown, insertion of a herpes virus episome or linear genome adjacent to a RAG-2 like gene would provide a master co-regulated RAG-2/RAG-2 locus acting subsequently through co-evolving slave RSS sites in immunoglobulin or T-cell receptor genes. Co-evolving slave RSS could arise either from additional herpes or transposon insertions and gene duplication events or from co-evolution of endogenous sequences with some similarity to transposon or herpes virus termini in other genes such as those encoding B- and T-lymphocyte receptors (Figure 1). In contrast to the “RAG transposon” model, the co-regulatory model does not require the existence of a composite RAG-1/RAG-2 transposase or transposon and can also account for the experimental structure of the current RAG-1/RAG-2-like genes in the sea urchin and other deuterostomes that do not undergo V(D)J recombination.