P. marinus are candidates for enzymes that may initiate this gene rearrangement. Expression of the rearranged gene results in a complete receptor that can be attached to the cell membrane by glycosylphosphatidylinositol (GPI) linkage of its stalk. Bottom panel: an individual lymphocyte undergoes somatic gene rearrangement to produce a unique VLR receptor. These receptors can be tethered to the surface of the lymphocyte via the GPI linkage or can be secreted into the blood. Unique somatic rearrangement events in each developing lymphocyte generate a repertoire of VLR receptors of differing specificities. Adapted from Pancer, Z., and Cooper, M.D.: Annu. Rev. Immunol. 2006, 24:497–518.
In vertebrates, evolution of the locus results in a multipart antigen-receptor locus that can be rearranged by RAG-mediated somatic recombination Recombination separates the RAG genes from the TR-tagged gene segments Insertion of the transposon into a V-type Ig receptor gene splits the gene into two TR TRRAG1 gene excision site RAG2 gene RAG1 gene RSS RSS RAG2 gene Transposon-derived RAG1/2-like gene cluster in a deuterostome ancestor Transposase activity can excise the transposon at terminal repeat sequences and reinsert it at a new location in the genome J JVV V-type Ig-like domain
Fig. 5.26 Integration of a transposon into a V-type immunoglobulin receptor gene is thought to have given rise to the T-cell receptor and immunoglobulin genes.
respectively, and VLRC cells appear more closely related to the VLRA lineage. For example, VLRA-expressing lymphocytes also express genes similar to some mammalian T-cell cytokine genes, suggesting an even closer similarity to our own RAG-dependent adaptive immune system than was previously appreciated.
repertoire of immunoglobulin-like genes appeared abruptly in the cartilaginous fishes.
Within the vertebrates, we can trace the development of immune functions from the agnathans through the cartilaginous fishes (sharks, skates, and rays) to the bony fishes, then to the amphibians, to reptiles and birds, and finally to mammals. RAG-dependent V(D)J recombination has not been found in agnathans, other chordates, or any invertebrate. The origins of RAG-dependent adaptive immunity are now becoming clearer as the genome sequences of many more animals become available. The first clue was that RAG-dependent recombination shares many features with the transposition mechanism of DNA transposons—mobile genetic elements that encode their own transposase, an enzymatic activity that allows them to excise from one site in the genome and reinsert themselves elsewhere. The mammalian RAG complex can act as a transposase in vitro, and even the structure of the RAG genes, which lie close together in the chromosome and lack the usual introns of mammalian genes, is reminiscent of a transposon.