Article abstract
Nature Immunology 8, 647 - 656 (2007)
Published online: 29 April 2007 | doi:10.1038/ni1463
Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase
Igor B Rogozin1,2,6, Lakshminarayan M Iyer1,6, Lizhi Liang3, Galina V Glazko4, Victoria G Liston5, Youri I Pavlov5, L Aravind1 & Zeev Pancer3
Abstract
The variable lymphocyte receptors (VLRs) of jawless vertebrates such as lamprey and hagfish are composed of highly diverse modular leucine-rich repeats. Each lymphocyte assembles a unique VLR by rearrangement of the germline gene. In the lamprey genome, we identify here about 850 distinct cassettes encoding leucine-rich repeat modules that serve as sequence templates for the hypervariable VLR repertoires. The data indicate a gene conversion–like process in VLR diversification. Genomic analysis suggested a link between the VLR and platelet glycoprotein receptors. Lamprey lymphocytes express two putative deaminases of the AID-APOBEC family that may be involved in VLR diversification, as indicated by in vitro mutagenesis and recombination assays. Vertebrate acquired immunity could have therefore originated from lymphocyte receptor diversification by an ancestral AID-like DNA cytosine deaminase.
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
- Institute of Cytology and Genetics, Novosibirsk 630090, Russia.
- Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21202, USA.
- Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
- Eppley Institute for Research in Cancer and Allied Diseases, Nebraska Medical Center, Omaha, Nebraska 68198, USA.
- These authors contributed equally to this work.
Correspondence to: Zeev Pancer3 e-mail: pancer@comb.umbi.umd.edu
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