Genomic donor cassette sharing during VLRA and VLRC assembly in jawless vertebrates

• Type of Material: Article
• Authors: Sabyasachi Das, Emory University; Jianxu Li, Emory University; Stephen J. Holland, Max Planck Institute of Immunobiology and Epigenetics; Lakshminarayan M. Iyer, National Institutes of Health; Masayuki Hirano, Emory University; Michael Schorpp, Max Planck Institute of Immunobiology and Epigenetics; L. Aravind, National Institutes of Health; Max Dale Cooper, Emory University; Thomas Boehm, Max Planck Institute of Immunobiology and Epigenetics
• Language: English
• Date: 2014-10-14
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: Freely available online through the PNAS open access option.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1415580111
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 111
• Issue: 41
• Start Page: 14828
• End Page: 14833
• Grant/Funding Information: This work was supported by the Max Planck Society; and has received funding from the European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013); ERC Grant Agreement No. ERC-2012-AdG–323126.; Work by L.M.I. and L.A. is funded by the Intramural Research Program of the National Institutes of Health (NIH), Department of Health and Human Services.; Work by S.D., J.L., M.H., and M.D.C. was supported by NIH Grants AI072435 and GM100151; and the Georgia Research Alliance.
• Keywords: HAGFISH; ORGANIZATION; GENE; LOCUS; Multidisciplinary Sciences; EVOLUTION; Science & Technology - Other Topics; adaptive immunity; IDENTIFICATION; molecular evolution; ADAPTIVE IMMUNE-SYSTEMS; Science & Technology; SEA LAMPREY; DIVERSIFICATION; selection; agnatha; VARIABLE LYMPHOCYTE-RECEPTOR
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894 Lampreys possess two T-like lymphocyte lineages that express either variable lymphocyte receptor (VLR) A or VLRC antigen receptors. VLRA⁺ and VLRC⁺ lymphocytes share many similarities with the two principal T-cell lineages of jawed vertebrates expressing the αβ and γδ T-cell receptors (TCRs). During the assembly of VLR genes, several types of genomic cassettes are inserted, in step-wise fashion, into incomplete germ-line genes to generate themature forms of antigen receptor genes. Unexpectedly, the structurally variable components of VLRA and VLRC receptors often possess partially identical sequences; this phenomenon of module sharing between these two VLR isotypes occurs in both lampreys and hagfishes. By contrast, VLRA and VLRC molecules typically do not share their building blocks with the structurally analogous VLRB receptors that are expressed by Blike lymphocytes. Our studies reveal that VLRA and VLRC germ-line genes are situated in close proximity to each other in the lamprey genome and indicate the interspersed arrangement of isotype-specific and shared genomic donor cassettes; these features may facilitate the shared cassette use. The genomic structure of the VLRA/ VLRC locus in lampreys is reminiscent of the interspersed nature of the TCRA/TCRD locus in jawed vertebrates that also allows the sharing of some variable gene segments during the recombinatorial assembly of TCR genes.