Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys

Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys
Title:
Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys
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Proceedings of the National Academy of Sciences of the United States of America
Keywords:
Publication Date:
19 March 2018
Citation:
Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys Stephen J. Holland, Lesley M. Berghuis, Justin J. King, Lakshminarayan M. Iyer, Katarzyna Sikora, Heather Fifield, Sarah Peter, Emma M. Quinlan, Fumiaki Sugahara, Prashant Shingate, Inês Trancoso, Norimasa Iwanami, Elena Temereva, Christine Strohmeier, Shigeru Kuratani, Byrappa Venkatesh, Guillaume Evanno, L. Aravind, Michael Schorpp, Mani Larijani, Thomas Boehm Proceedings of the National Academy of Sciences Apr 2018, 115 (14) E3211-E3220; DOI: 10.1073/pnas.1720871115
Abstract:
Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members of the APOBEC3 branch are involved in antiviral defense, whereas AID contributes to diversification of antibody repertoires in jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In the extant jawless vertebrate, the lamprey, two members of the AID/APOBEC family are implicated in the generation of somatic diversity of the variable lymphocyte receptors (VLRs). Expression studies linked CDA1 and CDA2 genes to the assembly of VLRA/C genes in T-like cells and the VLRB genes in B-like cells, respectively. Here, we identify and characterize several CDA1-like genes in the larvae of different lamprey species and demonstrate that these encode active cytidine deaminases. Structural comparisons of the CDA1 variants highlighted substantial differences in surface charge; this observation is supported by our finding that the enzymes require different conditions and substrates for optimal activity in vitro. Strikingly, we also found that the number of CDA-like genes present in individuals of the same species is variable. Nevertheless, irrespective of the number of different CDA1-like genes present, all lamprey larvae have at least one functional CDA1-related gene encoding an enzyme with predicted structural and chemical features generally comparable to jawed vertebrate AID. Our findings suggest that, similar to APOBEC3 branch expansion in jawed vertebrates, the AID/APOBEC family has undergone substantial diversification in lamprey, possibly indicative of multiple distinct biological roles.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
S.J.H. and T.B. are supported by the Max Planck Society, the Deutsche Forschungsgemeinschaft through SFB 746, and the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013), ERC Grant agreement 323126. M.L. is supported by a Canadian Cancer Society Research Institute innovation grant and Natural Sciences and Engineering Research Council (NSERC) Discovery Grant 2015-047960. E.M.Q. is supported by an NSERC postgraduate doctoral scholarship, and J.J.K. is supported by a Canadian Institutes of Health Research doctoral fellowship. L.M.I. and L.A. are supported by the NIH and the intramural funds of the National Library of Medicine at the NIH.
Description:
ISSN:
0027-8424
1091-6490
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