Evolution of the RAG1-RAG2 locus: both proteins came from the same transposon.

Vladimir V Kapitonov,Eugene V Koonin

doi:10.1186/s13062-015-0055-8

Vladimir V Kapitonov, Eugene V Koonin

Open Access

https://doi.org/10.1186/s13062-015-0055-8

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Abstract

The RAG1 and RAG2 proteins are essential subunits of the V(D)J recombinase that is required for the generation of the enormous variability of antibodies and T-cell receptors in jawed vertebrates. It was demonstrated previously that the 600-aa catalytic core of RAG1 evolved from the transposase of the Transib superfamily transposons. However, although homologs of RAG1 and RAG2 genes are adjacent in the purple sea urchin genome, a transposon encoding both proteins so far has not been reported. Here we describe such transposons in the genomes of green sea urchin, a starfish and an oyster. Comparison of the domain architectures of the RAG1 homologs in these transposons, denoted TransibSU, and other Transib superfamily transposases provides for reconstruction of the structure of the hypothetical TransibVDJ transposon that gave rise to the VDJ recombinases at the onset of vertebrate evolution some 500 million years ago.ReviewersThis article was reviewed by Mart Krupovic and I. King Jordan.Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-015-0055-8) contains supplementary material, which is available to authorized users.

Highlights

The Recombination activating gene 1 (RAG1) and Recombination activation gene 2 (RAG2) proteins are essential subunits of the V(D)J recombinase that is required for the generation of the enormous variability of antibodies and T-cell receptors in jawed vertebrates
We have shown previously that the 600-aa catalytic core of RAG1 and VDJ recombination signal sequences (RSS) has evolved from the transposase and terminal inverted repeats (TIRs) of a Transib superfamily transposon, respectively, and this event has been mapped to the common ancestor of jawed vertebrates that lived about 500 million years ago (MYA) [8]
The findings reported here strongly suggest that the direct ancestor of the vertebrate V(D)J recombinase was a hypothetical TransibVDJ transposon that encoded both the Transib transposase containing the RING domain (RAG1L protein) and the Kelch-PHD protein (RAG2L)

Summary

Introduction

The RAG1 and RAG2 proteins are essential subunits of the V(D)J recombinase that is required for the generation of the enormous variability of antibodies and T-cell receptors in jawed vertebrates. It was demonstrated previously that the 600-aa catalytic core of RAG1 evolved from the transposase of the Transib superfamily transposons. Homologs of RAG1 and RAG2 genes are adjacent in the purple sea urchin genome, a transposon encoding both proteins so far has not been reported. We describe such transposons in the genomes of green sea urchin, a starfish and an oyster. Comparison of the domain architectures of the RAG1 homologs in these transposons, denoted TransibSU, and other Transib superfamily transposases provides for reconstruction of the structure of the hypothetical TransibVDJ transposon that gave rise to the VDJ recombinases at the onset of vertebrate evolution some 500 million years ago

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