Antigen receptor gene assembly in jawless vertebrates resembles LINE-1 retrotransposition. Eptatretus burgeri

Jawless vertebrates, the most phylogenetically distant vertebrates from mammals, possess an alternative form of adaptive immunity, which is mediated by antigen receptors called variable lymphocyte receptors (VLRs)1-5. Diverse VLR genes, which consist almost entirely of several leucine-rich repeats (LRRs), are generated by gene rearrangement using a mechanism that is different than that of V(D)J recombination in jawed vertebrates. To generate mature VLR genes, several LRR gene segments are chosen from the many scattered around the germline VLR gene and copied into the germline gene1,3,6,7. Whereas the origin of V(D)J recombination is thought to be from a DNA transposon8-10, the origin of VLR gene assembly is unknown. Here, we demonstrate that the initial event in the VLR gene assembly, LRR segment insertion, is similar to LINE-1 retrotransposition11-13. We cloned partially assembled VLR genes in hagfish and found that some have structures similar to those of LINE-1 retrotransposon insertions. They contain target site duplications (TSD) or deletions of various sizes at the site of LRR segment insertion. The generation of direct repeats also suggests that VLR gene assembly can be initiated by a DNA nick. These data suggest that the VLR alternative adaptive immune system also has its origins in a transposable element, but one which is different from the one involved in the origin of V(D)J recombination in jawed vertebrates.