Nature 374, 168 - 173 (09 March 2002); doi:10.1038/374168a0

A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks

Andrew S.  Greenberg^*, David  Avila^†, Marianne  Hughes^‡, Austin Hughes^‡, E. Churchill McKinney^* & Martin F.  Flajnik^*

^*Department of Microbiology and Immunology, University of Miami School of Medicine, PO Box 016960 (R-138), Miami, Florida 33101, USA
^†Basel Institute for Immunology, Grenzacherstrasse 487, CH-4058 Basel, Switzerland
^‡ Department of Biology, 208 Erwin W. Mueller Laboratory, Pennsylvania State University, University Park, Pennsylvania 16802, USA

IMMUNOGLOBULIN and T-cell receptor (TCR) molecules are central to the adaptive immune system. Sequence conservation, similarities in domain structure, and usage of similar recombination signal sequences and recombination machinery indicate that there was probably a time during evolution when an ancestral receptor diverged to the modern-day immunoglobulin and TCR^1–3. Other molecules that undergo rearrangement have not been described in vertebrates, nor have intermediates been identified that have features of both these gene families. We report here the isolation of a new member of the immunoglobulin superfamily from the nurse shark, Ginglymostoma cirratum, which contains one variable and five constant domains and is found as a dimer in serum. Analyses of complementary DNA clones show extensive sequence diversity within variable domains, which is generated by both rearrangement and somatic diversification mechanisms. Our results suggest that rearranging loci distinct from immunoglobulin and TCR have arisen during evolution.

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