Rearrangement of immunoglobulin genes in shark germ cells.
The variable (V), (diversity [D]), and joining (J) region recombinases (recombination activating genes [RAGs]) can perform like transposases and are thought to have initiated development of the adaptive immune system in early vertebrates by splitting archaic V genes with transposable elements. In cartilaginous fishes, the immunoglobulin (Ig) light chain genes are organized as multiple VJ-constant (C) clusters; some loci are capable of rearrangement while others contain fused VJ. The latter may be key to understanding the evolutionary role of RAG. Are they relics of the archaic genes, or are they results of rearrangement in germ cells? Our data suggest that some fused VJ genes are not only recently rearranged, but also resulted from RAG-like activity involving hairpin intermediates. Expression studies show that these, like some other germline-joined Ig sequences, are expressed at significant levels only early in ontogeny. We suggest that a rejoined Ig gene may not merely be a sequence restricting antibody diversity, but is potentially a novel receptor no longer tied to somatic RAG expression and rearrangement. From the combined data, we arrived at the unexpected conclusion that, in some vertebrates, RAG is still an active force in changing the genome.
Lee
S S
SS
Department of Physiology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
Fitch
D
D
Flajnik
M F
MF
Hsu
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005854:Germ Cells / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012754:Sharks / Q000235:genetics* / Q000276:immunology*
D017931:DNA Primers; D004247:DNA