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.
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15 May 2000
Article|
May 08 2000
Rearrangement of Immunoglobulin Genes in Shark Germ Cells
Susan S. Lee,
Susan S. Lee
aDepartment of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203
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David Fitch,
David Fitch
bDepartment of Biology, New York University, New York, New York 10003
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Martin F. Flajnik,
Martin F. Flajnik
cDepartment of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201
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Ellen Hsu
Ellen Hsu
aDepartment of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203
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Susan S. Lee
aDepartment of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203
David Fitch
bDepartment of Biology, New York University, New York, New York 10003
Martin F. Flajnik
cDepartment of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201
Ellen Hsu
aDepartment of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203
Abbreviations used in this paper: FR, framework region; Myr BP, million years before present; RAG, recombination activating gene; RSS, recombination signal sequence(s); RT, reverse transcription; TdT, terminal deoxynucleotidyl transferase.
Received:
December 13 1999
Revision Requested:
February 22 2000
Accepted:
February 23 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (10): 1637–1648.
Article history
Received:
December 13 1999
Revision Requested:
February 22 2000
Accepted:
February 23 2000
Citation
Susan S. Lee, David Fitch, Martin F. Flajnik, Ellen Hsu; Rearrangement of Immunoglobulin Genes in Shark Germ Cells. J Exp Med 15 May 2000; 191 (10): 1637–1648. doi: https://doi.org/10.1084/jem.191.10.1637
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