Origin and evolution of the adaptive immune system: genetic events and selective pressures

The adaptive immune system (AIS) in mammals, which is centred on lymphocytes bearing antigen receptors that are generated by somatic recombination, arose approximately 500 million years ago in jawed fish. This intricate defence system consists of many molecules, mechanisms and tissues that are not present in jawless vertebrates. Two macroevolutionary events are believed to have contributed to the genesis of the AIS: the emergence of the recombination-activating gene (RAG) transposon, and two rounds of whole-genome duplication. It has recently been discovered that a non-RAG-based AIS with similarities to the jawed vertebrate AIS — including two lymphoid cell lineages — arose in jawless fish by convergent evolution. We offer insights into the latest advances in this field and speculate on the selective pressures that led to the emergence and maintenance of the AIS.

[1]  C. Markert,et al.  Evolution of the Gene , 1948, Nature.

[2]  R. Good,et al.  THE EVOLUTION OF THE IMMUNE RESPONSE III. IMMUNOLOGIC RESPONSES IN THE LAMPREY , 1964 .

[3]  G. Edelman,et al.  Phylogenetic origins of antibody structure. I. Multichain structure of immunoglobulins in the smooth dogfish (Mustelus canis). , 1965 .

[4]  D. Linthicum,et al.  Immunologic responses of Pacific hagfish. 3. Serum antibodies to cellular antigens. , 1970, Journal of immunology.

[5]  Dr. Susumu Ohno.  Evolution by Gene Duplication , 1970, Springer Berlin Heidelberg.

[6]  M. Cohn,et al.  Variability in the Lambda Light Chain Sequences of Mouse Antibody , 1970, Nature.

[7]  G. Litman,et al.  The evolution of the immune response. VIII. Structural studies of the lamprey immuoglobulin. , 1970, Journal of immunology.

[8]  R. Zinkernagel,et al.  Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytes choriomeningitis , 1974, Nature.

[9]  S. Tonegawa.  Reiteration frequency of immunoglobulin light chain genes: further evidence for somatic generation of antibody diversity. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Hitoshi Sakano,et al.  Sequences at the somatic recombination sites of immunoglobulin light-chain genes , 1979, Nature.

[11]  S. Tonegawa,et al.  Somatic generation of antibody diversity. , 1976, Nature.

[12]  Y. Chien,et al.  A Murine T Cell Receptor Gene Complex: Isolation, Structure and Rearrangement , 1984, Immunological reviews.

[13]  K. Johnson.  An Update. , 1984, Journal of food protection.

[14]  G. Litman,et al.  Major reorganization of immunoglobulin VH segmental elements during vertebrate evolution , 1986, Nature.

[15]  P. Smaglik,et al.  New Perspectives , 2011, Hormone Research in Paediatrics.

[16]  J. Weill,et al.  A hyperconversion mechanism generates the chicken light chain preimmune repertoire , 1987, Cell.

[17]  J. Allison,et al.  Limited diversity of T-cell receptor gamma-chain expression of murine Thy-1+ dendritic epidermal cells revealed by V gamma 3-specific monoclonal antibody. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[18]  D. Schatz,et al.  RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. , 1990, Science.

[19]  R. Becker,et al.  Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes: Implications for the generation of antibody diversity , 1990, Cell.

[20]  M. Wilson,et al.  Evolution of immunoglobulin light chain genes: analysis of Xenopus IgL isotypes and their contribution to antibody diversity. , 1991, The EMBO journal.

[21]  J. Marchalonis,et al.  Complete sequence of a cDNA clone specifying sandbar shark immunoglobulin light chain: gene organization and implications for the evolution of light chains. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Litman,et al.  Somatic variation precedes extensive diversification of germline sequences and combinatorial joining in the evolution of immunoglobulin heavy chain diversity , 1993, The Journal of experimental medicine.

[23]  J. Klein,et al.  The molecular descent of the major histocompatibility complex. , 1993, Annual review of immunology.

[24]  M. Flajnik,et al.  Isolation of a shark immunoglobulin light chain cDNA clone encoding a protein resembling mammalian kappa light chains: implications for the evolution of light chains. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Marchalonis,et al.  Genomic clone for sandbar shark lambda light chain: generation of diversity in the absence of gene rearrangement. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[26]  P. R. Sibbald,et al.  CDR3 length in antigen-specific immune receptors , 1994, The Journal of experimental medicine.

[27]  J. Kaufman,et al.  A “Minimal Essential Mhc” and an “Unrecognized Mhc”: Two Extremes in Selection for Polymorphism , 1995, Immunological reviews.

[28]  C. Thompson,et al.  New insights into V(D)J recombination and its role in the evolution of the immune system. , 1995, Immunity.

[29]  Yoshimasa Tanaka,et al.  Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γδ T cells , 1995 .

[30]  K Panico,et al.  Care in the community , 1995, Nature.

[31]  G. Warr,et al.  IgY: clues to the origins of modern antibodies. , 1995, Immunology today.

[32]  Austin Hughes,et al.  A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks , 1995, Nature.

[33]  T. Ikemura,et al.  Chromosomal localization of the proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Lode Wyns,et al.  Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme , 1996, Nature Structural Biology.

[35]  N. Katsanis.  Paralogy mapping: identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci , 1996 .

[36]  L. Du Pasquier,et al.  Is Xenopus IgX an analog of IgA? , 1996, European journal of immunology.

[37]  E. Fisher,et al.  Paralogy mapping: identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci. , 1996, Genomics.

[38]  J. Marchalonis,et al.  A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[39]  A. Hughes,et al.  A novel “chimeric” antibody class in cartilaginous fish: IgM may not be the primordial immunoglobulin , 1996, European journal of immunology.

[40]  M. Kasahara,et al.  Chromosomal duplication and the emergence of the adaptive immune system. , 1997, Trends in genetics : TIG.

[41]  G. Warr,et al.  A novel chimeric Ig heavy chain from a teleost fish shares similarities to IgD. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Musanori Kasahara.  What do the paralogous regions in the genome tell us about the origin of the adaptive immune system? , 1998, Immunological reviews.

[43]  S. Kaattari,et al.  Varied redox forms of teleost IgM: an alternative to isotypic diversity? , 1998, Immunological reviews.

[44]  M. Flajnik,et al.  Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: possible role in antigen-driven reactions in the absence of germinal centers. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Charlemagne,et al.  T‐cell receptors in ectothermic vertebrates , 1998, Immunological reviews.

[46]  Takeshi Matsunaga,et al.  What brought the adaptive immune system to vertebrates? ‐ The jaw hypothesis and the seahorse , 1998, Immunological reviews.

[47]  M. Flajnik.  Churchill and the immune system of ectothermic vertebrates , 1998, Immunological reviews.

[48]  M. Kasahara.  The chromosomal duplication model of the major histocompatibility complex , 1999, Immunological reviews.

[49]  M. Kasahara.  Genome dynamics of the major histocompatibility complex: insights from genome paralogy , 1999, Immunogenetics.

[50]  J. Kaufman,et al.  Co-evolving genes in MHC haplotypes: the "rule" for nonmammalian vertebrates? , 1999, Immunogenetics.

[51]  J. Bluestone,et al.  TCRγδ cells and viruses , 1999 .

[52]  J. Marchalonis,et al.  'Big Bang' emergence of the combinatorial immune system. , 1999, Developmental and comparative immunology.

[53]  T J Gibson,et al.  Evidence in favour of ancient octaploidy in the vertebrate genome. , 2000, Biochemical Society transactions.

[54]  T. Honjo,et al.  Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme , 2000, Cell.

[55]  J. Trowsdale,et al.  Genetic and functional relationships between MHC and NK receptor genes. , 2001, Immunity.

[56]  M. Flajnik,et al.  Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. , 2001, Immunity.

[57]  A. Hughes,et al.  Pattern and timing of gene duplication in animal genomes. , 2001, Genome research.

[58]  André Gilles,et al.  Evidence of en bloc duplication in vertebrate genomes , 2002, Nature Genetics.

[59]  P. Holland,et al.  Were vertebrates octoploid? , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[60]  K. Kärre.  NK Cells, MHC Class I Molecules and the Missing Self , 2002, Scandinavian journal of immunology.

[61]  J. Klein,et al.  Lamprey lymphocyte-like cells express homologs of genes involved in immunologically relevant activities of mammalian lymphocytes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[62]  D. Tranchina,et al.  Hypermutation in shark immunoglobulin light chain genes results in contiguous substitutions. , 2002, Immunity.

[63]  D. Littman,et al.  Regulation of the TCRα repertoire by the survival window of CD4+CD8+ thymocytes , 2002, Nature Immunology.

[64]  M. Flajnik.  Comparative analyses of immunoglobulin genes: surprises and portents , 2002, Nature Reviews Immunology.

[65]  J. Klein,et al.  Isolation and characterization of lymphocyte-like cells from a lamprey , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[66]  김희라.  Waiting for Godot에 나타난 희망의 구조 , 2003 .

[67]  C. Amemiya,et al.  Lineage-restricted retention of a primitive immunoglobulin heavy chain isotype within the Dipnoi reveals an evolutionary paradox , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[68]  B. Plougastel,et al.  Immune functions encoded by the natural killer gene complex , 2003, Nature Reviews Immunology.

[69]  E. Danchin,et al.  Evolution of the proto-MHC ancestral region: more evidence for the plesiomorphic organisation of human chromosome 9q34 region , 2003, Immunogenetics.

[70]  I. Rigoutsos,et al.  Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: “waiting for Godot” , 2003, Immunogenetics.

[71]  J. Klein,et al.  Prototypic T cell receptor and CD4-like coreceptor are expressed by lymphocytes in the agnathan sea lamprey. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[72]  L. Pilström,et al.  A cluster type organization of the loci of the immunoglobulin light chain in Atlantic cod (Gadus morhua L.) and rainbowttrout (Oncorhynchus mykiss Walbaum) indicated by nucleotide sequences of cDNAs and hybridization analysis , 2004, Immunogenetics.

[73]  M. Kasahara,et al.  Natural killer cell receptors in the horse: evidence for the existence of multiple transcribed LY49 genes , 2004, European journal of immunology.

[74]  Sue Povey,et al.  Gene map of the extended human MHC , 2004, Nature Reviews Genetics.

[75]  Alexandre Vienne,et al.  Evolution of the proto-MHC ancestral region: more evidence for the plesiomorphic organisation of human chromosome 9q34 region , 2004, Immunogenetics.

[76]  Klaas Vandepoele,et al.  Major events in the genome evolution of vertebrates: paranome age and size differ considerably between ray-finned fishes and land vertebrates. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[77]  L. Du Pasquier,et al.  Immunoglobulin superfamily receptors in protochordates: before RAG time , 2004, Immunological reviews.

[78]  Charles E. Chapple,et al.  Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype , 2004, Nature.

[79]  M. Flajnik,et al.  Evolution of innate and adaptive immunity: can we draw a line? , 2004, Trends in immunology.

[80]  Y. Kohara,et al.  Transcriptome analysis of hagfish leukocytes: a framework for understanding the immune system of jawless fishes. , 2004, Developmental and comparative immunology.

[81]  D. Larhammar,et al.  Numerous groups of chromosomal regional paralogies strongly indicate two genome doublings at the root of the vertebrates , 2004, Journal of Structural and Functional Genomics.

[82]  Chris T. Amemiya,et al.  Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey , 2004, Nature.

[83]  M. Kasahara,et al.  On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates. , 2004, Trends in immunology.

[84]  S. Hedrick,et al.  The acquired immune system: a vantage from beneath. , 2004, Immunity.

[85]  J. Rast,et al.  Immunoglobulin light chain class multiplicity and alternative organizational forms in early vertebrate phylogeny , 2004, Immunogenetics.

[86]  A. Hughes,et al.  2R or not 2R: Testing hypotheses of genome duplication in early vertebrates , 2004, Journal of Structural and Functional Genomics.

[87]  M. Flajnik,et al.  Shark immunity bites back: affinity maturation and memory response in the nurse shark, Ginglymostoma cirratum , 2005, European journal of immunology.

[88]  Y. Kohara,et al.  Hagfish Leukocytes Express a Paired Receptor Family with a Variable Domain Resembling Those of Antigen Receptors12 , 2005, The Journal of Immunology.

[89]  A. Xu,et al.  Genes “Waiting” for Recruitment by the Adaptive Immune System: The Insights from Amphioxus 1 , 2005, The Journal of Immunology.

[90]  J. Klein,et al.  The descent of the antibody-based immune system by gradual evolution. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[91]  Takashi Suzuki,et al.  Variable lymphocyte receptors in hagfish. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[92]  S. Hedges,et al.  Molecular phylogeny and divergence times of deuterostome animals. , 2005, Molecular biology and evolution.

[93]  John P. Cannon,et al.  Reconstructing immune phylogeny: new perspectives , 2005, Nature Reviews Immunology.

[94]  J. Hansen,et al.  Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[95]  K. Jekosch,et al.  The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z , 2005, Nature Immunology.

[96]  J. Jurka,et al.  RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons , 2005, PLoS biology.

[97]  Galina V. Glazko,et al.  Diversity and Function of Adaptive Immune Receptors in a Jawless Vertebrate , 2005, Science.

[98]  A. Poustka,et al.  Timing and mechanism of ancient vertebrate genome duplications -- the adventure of a hypothesis. , 2005, Trends in genetics : TIG.

[99]  Jonathan D. G. Jones,et al.  The plant immune system , 2006, Nature.

[100]  V. Stojanoff,et al.  Ancient evolutionary origin of diversified variable regions demonstrated by crystal structures of an immune-type receptor in amphioxus , 2006, Nature Immunology.

[101]  M. Kasahara,et al.  Variable domains in hagfish: NICIR is a polymorphic multigene family expressed preferentially in leukocytes and is related to lamprey TCR-like , 2006, Immunogenetics.

[102]  J. Stenvik,et al.  Antibody repertoire development in teleosts--a review with emphasis on salmonids and Gadus morhua L. , 2006, Developmental and comparative immunology.

[103]  M. Flajnik,et al.  IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[104]  Yaofeng Zhao,et al.  Identification of IgF, a hinge-region-containing Ig class, and IgD in Xenopus tropicalis , 2006, Proceedings of the National Academy of Sciences.

[105]  A. Voskoboynik,et al.  fester, A candidate allorecognition receptor from a primitive chordate. , 2006, Immunity.

[106]  Katherine M. Buckley,et al.  The immune gene repertoire encoded in the purple sea urchin genome. , 2006, Developmental biology.

[107]  F. Hallböök,et al.  Conserved synteny between the Ciona genome and human paralogons identifies large duplication events in the molecular evolution of the insulin-relaxin gene family. , 2006, Molecular biology and evolution.

[108]  J. Rast,et al.  An ancient evolutionary origin of the Rag1/2 gene locus. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[109]  M. Flajnik,et al.  An evolutionarily mobile antigen receptor variable region gene: doubly rearranging NAR-TcR genes in sharks. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[110]  Anthony T Papenfuss,et al.  Reconstructing an Ancestral Mammalian Immune Supercomplex from a Marsupial Major Histocompatibility Complex , 2006, PLoS biology.

[111]  M. Criscitiello,et al.  Diverse Immunoglobulin Light Chain Organizations in Fish Retain Potential to Revise B Cell Receptor Specificities1 , 2006, The Journal of Immunology.

[112]  M. Thorndyke,et al.  Formation and Evolution of the Chordate Neurotrophin and Trk Receptor Genes , 2006, Brain, Behavior and Evolution.

[113]  Ki Jung Lim,et al.  Structural Diversity of the Hagfish Variable Lymphocyte Receptors* , 2006, Journal of Biological Chemistry.

[114]  M. McFall-Ngai.  Adaptive Immunity: Care for the community , 2007, Nature.

[115]  M. Kasahara,et al.  Two variable lymphocyte receptor genes of the inshore hagfish are located far apart on the same chromosome , 2007, Immunogenetics.

[116]  K. Lindblad-Toh,et al.  A unique T cell receptor discovered in marsupials , 2007, Proceedings of the National Academy of Sciences.

[117]  H. Sakano,et al.  Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice , 2007, Nature Immunology.

[118]  M. Kasahara,et al.  The 2R hypothesis: an update. , 2007, Current opinion in immunology.

[119]  Osamu Takeuchi,et al.  Genetic analysis of resistance to viral infection , 2007, Nature Reviews Immunology.

[120]  G. Glazko,et al.  Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase , 2007, Nature Immunology.

[121]  M. Flajnik,et al.  Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates , 2007 .

[122]  K. Asai,et al.  Expansion of signaling genes for adaptive immune system evolution in early vertebrates , 2008, BMC Genomics.

[123]  S. Desiderio,et al.  A plant homeodomain in RAG-2 that binds Hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. , 2007, Immunity.

[124]  M. Bonneville,et al.  Self/non‐self discrimination by human γδ T cells: simple solutions for a complex issue? , 2007 .

[125]  Nicholas H. Putnam,et al.  The amphioxus genome illuminates vertebrate origins and cephalochordate biology. , 2008, Genome research.

[126]  T. Ikawa,et al.  Adult T-cell progenitors retain myeloid potential , 2008, Nature.

[127]  Brantley R. Herrin,et al.  Structure and specificity of lamprey monoclonal antibodies , 2008, Proceedings of the National Academy of Sciences.

[128]  A. Bhandoola,et al.  The earliest thymic progenitors for T cells possess myeloid lineage potential , 2008, Nature.

[129]  Nicholas H. Putnam,et al.  The amphioxus genome and the evolution of the chordate karyotype , 2008, Nature.

[130]  J. Kaufman,et al.  Avian NK activities, cells and receptors. , 2008, Seminars in immunology.

[131]  Ian A. Wilson,et al.  Antigen Recognition by Variable Lymphocyte Receptors , 2008, Science.

[132]  Gene W. Yeo,et al.  Immunoglobulin light chain (IgL) genes in zebrafish: Genomic configurations and inversional rearrangements between (VL–JL–CL) gene clusters , 2008, Developmental and comparative immunology.

[133]  Brantley R. Herrin,et al.  Antibody responses of variable lymphocyte receptors in the lamprey , 2008, Nature Immunology.

[134]  L. Zakharova.  Evolution of adaptive immunity , 2009, Biology Bulletin.

[135]  Axel Meyer,et al.  Timing of genome duplications relative to the origin of the vertebrates: did cyclostomes diverge before or after? , 2008, Molecular biology and evolution.

[136]  G. Waldbieser,et al.  Patterns of Receptor Revision in the Immunoglobulin Heavy Chains of a Teleost Fish12 , 2009, The Journal of Immunology.

[137]  L. Aravind,et al.  Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen , 2009, Nature Structural &Molecular Biology.

[138]  D. Dreyfus.  Paleo-Immunology: Evidence Consistent with Insertion of a Primordial Herpes Virus-Like Element in the Origins of Acquired Immunity , 2009, PloS one.

[139]  J. Long,et al.  Devonian arthrodire embryos and the origin of internal fertilization in vertebrates , 2009, Nature.

[140]  T. Boehm.  One problem, two solutions , 2009, Nature Immunology.

[141]  Melanie Wilson,et al.  Immunoglobulin D enhances immune surveillance by activating antimicrobial, pro-inflammatory and B cell-stimulating programs in basophils , 2009, Nature Immunology.

[142]  Brantley R. Herrin,et al.  Dual Nature of the Adaptive Immune System in Lampreys , 2009, Nature.

[143]  A. Meyer,et al.  The evolutionary significance of ancient genome duplications , 2009, Nature Reviews Genetics.

[144]  J. Travis.  Origins. On the origin of the immune system. , 2009, Science.

[145]  M. Flajnik,et al.  High-affinity lamprey VLRA and VLRB monoclonal antibodies , 2009, Proceedings of the National Academy of Sciences.

[146]  Kevin R Lau,et al.  Characterization of arrangement and expression of the T cell receptor γ locus in the sandbar shark , 2009, Proceedings of the National Academy of Sciences.