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Significance Recombination activating gene (RAG)-mediated variable, diversity, and joining [V(D)J] gene recombination is the hallmark of the adaptive immunity that only exists in jawed vertebrates. The evolutionary origin of RAG remains largely unknown although many hypotheses have been proposed. This study indicates that a RAG1-like DNA fragment (bfRAG1L ) from the invertebrate amphioxus might encode a functional central domain of vertebrate core RAG1. We show that bfRAG1L (if translated) is a virus-related protein that can degrade both DNA and RNA and is able to introduce V(D)J gene recombination in RAG1-deficient mice after the reconstitution of bfRAG1L into a core RAG1-like protein. In this paper, we propose a model for the evolutionary process of RAG1 in the combination of previous hypotheses, and it provides unique insights into the origin and evolution of RAG1.

An amphioxus RAG1-like DNA fragment encodes a functional central domain of vertebrate core RAG1