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The plasticity of immunoglobulin gene systems in evolution

Authors

  • Ellen Hsu,

    Corresponding author
    1. Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY, USA.
      * Ellen Hsu
      Department of Physiology and Pharmacology
      State University of New York Health Science Center at Brooklyn
      450 Clarkson Ave., Box 31
      Brooklyn, NY 11203
      USA
      Fax: 1 718 270 3103
      E-mail: hsue@hscbklyn.edu
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  • Nicolas Pulham,

    1. Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY, USA.
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  • Lynn L. Rumfelt,

    1. Department of Immunology, University of Toronto, Ontario, Canada.
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  • Martin F. Flajnik

    1. Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
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* Ellen Hsu
Department of Physiology and Pharmacology
State University of New York Health Science Center at Brooklyn
450 Clarkson Ave., Box 31
Brooklyn, NY 11203
USA
Fax: 1 718 270 3103
E-mail: hsue@hscbklyn.edu

Abstract

Summary:  The mechanism of recombination-activating gene (RAG)-mediated rearrangement exists in all jawed vertebrates, but the organization and structure of immunoglobulin (Ig) genes, as they differ in fish and among fish species, reveal their capability for rapid evolution. In systems where there can exist 100 Ig loci, exon restructuring and sequence changes of the constant regions led to divergence of effector functions. Recombination among these loci created hybrid genes, the strangest of which encode variable (V) regions that function as part of secreted molecules and, as the result of an ancient translocation, are also grafted onto the T-cell receptor. Genomic changes in V-gene structure, created by RAG recombinase acting on germline recombination signal sequences, led variously to the generation of fixed receptor specificities, pseudogene templates for gene conversion, and ultimately to Ig sequences that evolved away from Ig function. The presence of so many Ig loci in fishes raises interesting questions not only as to how their regulation is achieved but also how successive whole-locus duplications are accommodated by a system whose function in other vertebrates is based on clonal antigen receptor expression.

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