Ellen Hsu,1 Nicolas Pulham,1 Lynn L. Rumfelt,2 and Martin F. Flajnik3, Immunol Rev. 2006 April; 210: 8–26.
1 Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY, USA
2 Department of Immunology, University of Toronto, Ontario, Canada
3 Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA
Correspondence to: 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: email@example.com
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.