title: Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase.
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.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Rogozin
authors.forename: Lakshminarayan M
authors.initials: LM
authors.lastname: Iyer
authors.forename: Lizhi
authors.initials: L
authors.lastname: Liang
authors.forename: Galina V
authors.initials: GV
authors.lastname: Glazko
authors.forename: Victoria G
authors.initials: VG
authors.lastname: Liston
authors.forename: Youri I
authors.initials: YI
authors.lastname: Pavlov
authors.forename: L
authors.initials: L
authors.lastname: Aravind
authors.forename: Zeev
authors.initials: Z
authors.lastname: Pancer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D043525:Cytosine Deaminase / Q000145:classification* / Q000378:metabolism*; D019143:Evolution, Molecular; D016678:Genome / Q000235:genetics; D006801:Humans; D007798:Lampreys / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011946:Receptors, Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment
chemical_list: D011946:Receptors, Antigen; D043525:Cytosine Deaminase