Abstract
Phylogenetic studies of immunity have revealed that about 500 million years ago, two types of recombinatorial adaptive immune systems (AIS) arose in vertebrates. Jawed vertebrates diversify the repertoire of immunoglobulin-domain-based B and T cell antigen receptors mainly through the rearrangement of gene segments and somatic hypermutation, whereas an alternative AIS of jawless vertebrates is based on variable lymphocyte receptors (VLRs) which diversify through recombinatorial usage of leucine-rich repeat (LRR) units. None of the fundamental recognition elements of jawed vertebrates AIS have been found in jawless vertebrates. Despite differences in molecular architecture, the parallel ‘two-arms’ of the AIS evolved within the context of preexisting innate immunity and maintained over a long period of time in jawed and jawless vertebrates, respectively, as a consequence of powerful and enduring evolutionary selection pressure by pathogens and other factors.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agrawal A, Eastman QM, Schatz DG (1998) Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 394:744–751
Alder MN, Rogozin IB, Iyer LM, Glazko GV, Cooper MD, Pancer Z (2005) Diversity and function of adaptive immune receptors in a jawless vertebrate. Science 310:1970–1973
Alder MN, Herrin BR, Sadlonova A, Stockard CR, Grizzle WE, Gartland LA, Gartland GL, Boydston JA, Turnbough CL Jr, Cooper MD (2008) Antibody responses of variable lymphocyte receptors in the lamprey. Nat Immunol 9:319–327
Boehm T, McCurley N, Sutoh Y, Schorpp M, Kasahara M, Cooper MD (2012) VLR-based adaptive immunity. Annu Rev Immunol 30:203–220
Buchanan SG, Gay NJ (1996) Structural and functional diversity in the leucine-rich repeat family of proteins. Prog Biophys Mol Biol 65:1–44
Cannon JP, Haire RN, Litman GW (2002) Identification of diversified genes that contain immunoglobulin-like variable regions in a protochordate. Nat Immunol 3:1200–1207
Cooper MD, Alder MN (2006) The evolution of adaptive immune systems. Cell 124:815–822
Cooper MD, Peterson RD, Good RA (1965) Delineation of the thymic and bursal lymphoid systems in the chicken. Nature 205:143–146
Das S, Hirano M, Aghaallaei N, Bajoghli B, Boehm T, Cooper MD (2013) Organization of lamprey variable lymphocyte receptor C locus and repertoire development. Proc Natl Acad Sci USA 110:6043–6048
Dudley DD, Chaudhuri J, Bassing CH, Alt FW (2005) Mechanism and control of V(D)J recombination versus class switch recombination: similarities and differences. Adv Immunol 86:43–112
Flajnik MF, Kasahara M (2010) Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat Rev Genet 11:47–59
Greaves MF, Roitt IM, Rose ME (1968) Effect of bursectomy and thymectomy on the responses of chicken peripheral blood lymphocytes to phytohaemagglutinin. Nature 220:293–295
Guo P, Hirano M, Herrin BR, Li J, Yu C, Sadlonova A, Cooper MD (2009) Dual nature of the adaptive immune system in lampreys. Nature 459:796–801
Hedrick SM, Cohen DI, Nielsen EA, Davis MM (1984) Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:149–153
Heimberg AM, Cowper-Sal-lari R, Semon M, Donoghue PC, Peterson KJ (2010) microRNAs reveal the interrelationships of hagfish, lampreys, and gnathostomes and the nature of the ancestral vertebrate. Proc Natl Acad Sci USA 107:19379–19383
Herrin BR, Alder MN, Roux KH, Sina C, Ehrhardt GR, Boydston JA, Turnbough CL Jr, Cooper MD (2008) Structure and specificity of lamprey monoclonal antibodies. Proc Natl Acad Sci USA 105:2040–2045
Hiom K, Gellert M (1997) A stable RAG1-RAG2-DNA complex that is active in V(D)J cleavage. Cell 88:65–72
Hirano M, Das S, Guo P, Cooper MD (2011) The evolution of adaptive immunity in vertebrates. Adv Immunol 109:125–157
Hoffmann JA, Kafatos FC, Janeway CA, Ezekowitz RA (1999) Phylogenetic perspectives in innate immunity. Science 284:1313–1318
Jung D, Alt FW (2004) Unraveling V(D)J recombination; insights into gene regulation. Cell 116:299–311
Kasamatsu J, Sutoh Y, Fugo K, Otsuka N, Iwabuchi K, Kasahara M (2010) Identification of a third variable lymphocyte receptor in the lamprey. Proc Natl Acad Sci USA 107:14304–14308
Klein J, Horejsi V (1997) Immunology. Blackwell Science, Oxford
Mayer WE, Uinuk-Ool T, Tichy H, Gartland LA, Klein J, Cooper MD (2002) Isolation and characterization of lymphocyte-like cells from a lamprey. Proc Natl Acad Sci USA 99:14350–14355
McCurley N, Hirano M, Das S, Cooper MD (2012) Immune related genes underpin the evolution of adaptive immunity in jawless vertebrates. Curr Genomics 13:86–94
Nagata T, Suzuki T, Ohta Y, Flajnik MF, Kasahara M (2002) The leukocyte common antigen (CD45) of the Pacific hagfish, Eptatretus stoutii: implications for the primordial function of CD45. Immunogenetics 54:286–291
Nagawa F, Kishishita N, Shimizu K, Hirose S, Miyoshi M, Nezu J, Nishimura T, Nishizumi H, Takahashi Y, Hashimoto S et al (2007) Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice. Nat Immunol 8:206–213
Najakshin AM, Mechetina LV, Alabyev BY, Taranin AV (1999) Identification of an IL-8 homolog in lamprey (Lampetra fluviatilis): early evolutionary divergence of chemokines. Eur J Immunol 29:375–382
Oettinger MA, Schatz DG, Gorka C, Baltimore D (1990) RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248:1517–1523
Pancer Z, Amemiya CT, Ehrhardt GR, Ceitlin J, Gartland GL, Cooper MD (2004) Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 430:174–180
Pancer Z, Saha NR, Kasamatsu J, Suzuki T, Amemiya CT, Kasahara M, Cooper MD (2005) Variable lymphocyte receptors in hagfish. Proc Natl Acad Sci USA 102:9224–9229
Rogozin IB, Iyer LM, Liang L, Glazko GV, Liston VG, Pavlov YI, Aravind L, Pancer Z (2007) Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase. Nat Immunol 8:647–656
Schatz DG, Oettinger MA, Baltimore D (1989) The V(D)J recombination activating gene, RAG-1. Cell 59:1035–1048
Takezaki N, Figueroa F, Zaleska-Rutczynska Z, Klein J (2003) Molecular phylogeny of early vertebrates: monophyly of the agnathans as revealed by sequences of 35 genes. Mol Biol Evol 20:287–292
Tonegawa S (1983) Somatic generation of antibody diversity. Nature 302:575–581
Uinuk-Ool T, Mayer WE, Sato A, Dongak R, Cooper MD, Klein J (2002) Lamprey lymphocyte-like cells express homologs of genes involved in immunologically relevant activities of mammalian lymphocytes. Proc Natl Acad Sci USA 99:14356–14361
Watson FL, Puttmann-Holgado R, Thomas F, Lamar DL, Hughes M, Kondo M, Rebel VI, Schmucker D (2005) Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science 309:1874–1878
Yanagi Y, Yoshikai Y, Leggett K, Clark SP, Aleksander I, Mak TW (1984) A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308:145–149
Zhang SM, Adema CM, Kepler TB, Loker ES (2004) Diversification of Ig superfamily genes in an invertebrate. Science 305:251–254
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Das, S., Hirano, M. (2013). Variable Lymphocyte Receptors in Jawless Vertebrates: Illuminating the Origin and Early Evolution of Adaptive Immunity. In: Pontarotti, P. (eds) Evolutionary Biology: Exobiology and Evolutionary Mechanisms. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38212-3_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-38212-3_17
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-38211-6
Online ISBN: 978-3-642-38212-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)