Chapter 3 : The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates

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This chapter focuses on how the essential components of the adaptive immune system-Ab, TcR, and MHC molecules-arose and began to interact. The major histocompatibility complex (MHC) molecules are loaded with their antigens by sophisticated pathways composed of various kinds of molecules, some of which are encoded by genes located in the MHC. In all jawed vertebrates examined thus far, the essential elements of the adaptive immune system are present. Despite years of functional experiments with invertebrates pointing to recognition of allo- and xenoantigens, none of the essential genetic components of the adaptive immune system in the jawed vertebrates were found in the first complete genomic sequences of invertebrates: an insect (the fruit fly ) and a nematode worm (). Therefore, the notion that invertebrates lack an adaptive immune system was strengthened, and the question became how invertebrates managed to survive without a system that is essential to jawed vertebrates. A key concept that has relevance no matter what the defense system might be is that pathogens that overcome all of their hosts may face a bleak evolutionary future, and so, in general, the virulence of pathogens is constrained and guided by the particular defenses that their host(s) evolve. Although there is little scope to observe the evolution of the immune system through fossils, it seems likely that the adaptive immune system of the jawed vertebrates also evolved in steps, none of which are separated between those organisms still living.

Citation: Kaufman J. 2011. The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates, p 41-55. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch3
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Image of FIGURE 1

An idealized tree, showing the relationships of the animals (and their defense systems). Phyla are indicated above the tree with thick lines; common names of species are indicated above the tree with thin lines; defense systems are indicated.

Citation: Kaufman J. 2011. The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates, p 41-55. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch3
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Image of FIGURE 2

A model for the evolution of the adaptive immune system of jawed vertebrates, from the primordial MHC (left) through two rounds of genome-wide duplication (middle) and subsequent silencing, deletion, and break up to give MHC paralogous regions (right). Black boxes indicate genes based on data from chickens; open boxes indicate genes based on data from other species. Gga and Hsa, chromosomes from chickens and humans, respectively.

Citation: Kaufman J. 2011. The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates, p 41-55. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch3
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Image of FIGURE 3

A model for the evolution of split variable region-containing antigen specific receptors by insertion of transposons (top), with cartoons indicating the location of the CDRs in a V domain (lower right) and the footprint of the CDRs on an MHC molecule (lower left). In the upper left, open circles indicate domains (Ig V type and C type), lines indicate transmembrane and cytoplasmic regions, filled circles indicate D and J segments of the protein, grey bars indicate membranes; one chain is gray to indicate that the molecule may or may not have been a dimer. In the upper right, boxes indicate genes or gene segments, and dotted lines indicate regions introduced by transposon insertion with the heavy black lines indicating RSS. In the cartoons, cylinders indicate α-helices, arrows indicate β-strands, thin lines indicate other conformations of the protein, the thick line indicates peptide bound to the MHC molecule, and the dotted ovals indicate the footprint of the CDRs from the α-chain and the β-chain of a TcR on a class I molecule.

Citation: Kaufman J. 2011. The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates, p 41-55. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch3
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Image of FIGURE 4

A model for the evolution of MHC molecules, from a class II β-chain-like homodimer to a class II heterodimer by duplication and divergence, and then to a class I chain with β2m by inversion. On the left, circles indicate domains (open for class II α-chain, gray-filled for class II β-chain, with SS for intrachain disulphide bond), lines indicate transmembrane and cytoplasmic regions, gray bars indicate membranes. On the right, boxes indicate exons (open for coding regions of class II α-chain, gray-filled for coding regions of class II β-chain, black-filled for 3′ untranslated region), P indicates promoter region with arrow showing direction of transcription, curved arrow around axis, and lightning bolts indicating an inversion around a central point with asymmetric breakpoints. Adapted from .

Citation: Kaufman J. 2011. The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates, p 41-55. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch3
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Image of FIGURE 5

A cartoon showing the relationship between coevolution of interacting genes and (recombinational) distance in the genome, as illustrated for the class I and TAP genes of the MHC. (Left) The TAP heterodimer and class I molecule(s) are embedded in a membrane. The number of well-expressed class I molecules ranges from three in humans to one in chickens. Similarly, the specificity of interaction with peptide (as indicated by the number and depth of indentations) increases for TAPs and may decrease for class I molecules from humans to chickens. (Right) Different regions of the MHC labelled in bold are separated by thin vertical lines, genes labeled in normal script are indicated by thick vertical lines, and distance between the TAP genes and the most distant class I gene is indicated by the horizontal arrow. Adapted from ; B. Walker et al., submitted.

Citation: Kaufman J. 2011. The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates, p 41-55. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch3
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Image of FIGURE 6

A cartoon showing that coevolution between the peptide-translocation specificity of TAP and the peptide-binding specificity of class I molecules leads to a single dominantly expressed class I molecule, as illustrated with the chicken MHC haplotype B4. Thin lines indicate peptides, a minus sign within a circle indicates negatively charged residue, a plus sign within a circle indicates positively charged residue, a circle indicates a hydrophobic residue. Adapted from .

Citation: Kaufman J. 2011. The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates, p 41-55. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch3
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1. Abi-Rached, L.,, A. Gilles,, T. Shiina,, P. Pontarotti, and, H. Inoko. 2002. Evidence of en bloc duplication in vertebrate genomes. Nat. Genet. 31: 100105.
2. Adema, C. M.,, L. A. Hertel,, R. D. Miller, and, E. S. Loker. 1997. A family of fibrinogen-related proteins that precipitates parasite-derived molecules is produced by an invertebrate after infection. Proc. Natl. Acad. Sci. USA 94: 86918696.
3. Amadou, C. 1999. Evolution of the Mhc class I region: the framework hypothesis. Immunogenetics 49: 362367.
4. Azumi, K.,, R. De Santis,, A. De Tomaso, I. Rigoutsos,, F. Yoshizaki,, M. R. Pinto,, R. Marino,, K. Shida,, M. Ikeda,, M. Arai,, Y. Inoue,, T. Shimizu,, N. Satoh,, D. S. Rokhsar,, L. Du Pasquier,, M. Kasahara,, M. Satake, and, M. Nonaka. 2003. Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: “waiting for Godot”. Immunogenetics 55: 570581.
5. Bajoghli, B.,, N. Aghaallaei,, I. Hess,, I. Rode,, N. Netuschil,, B. H. Tay,, B. Venkatesh,, J. K. Yu,, S. L. Kaltenbach,, N. D. Holland,, D. Diekhoff,, C. Happe,, M. Schorpp, and, T. Boehm. 2009. Evolution of genetic networks underlying the emergence of thymopoiesis in vertebrates. Cell 138: 186197.
6. Barribeau, S. M.,, J. Villinger, and, B. Waldman. 2008. Major histocompatibility complex based resistance to a common bacterial pathogen of amphibians. PLoS One 3: e2692.
7. Belov, K.,, J. E. Deakin,, A. T. Papenfuss,, M. L. Baker,, S. D. Melman,, H. V. Siddle,, N. Gouin,, D. L. Goode,, T. J. Sargeant,, M. D. Robinson,, M. J. Wakefield,, S. Mahony,, J. G. Cross,, P. V. Benos,, P. B. Samollow,, T. P. Speed,, J. A. Graves, and, R. D. Miller. 2006. Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex. PLoS Biol. 4: e46.
8. Benacerraf, B., and, R. N. Germain. 1978. The immune response genes of the major histocompatibility complex. Immunol. Rev. 38: 70119.
9. Bernstein, R. M.,, S. F. Schluter,, D. F. Lake, and, J. J. Marchalonis. 1994. Evolutionary conservation and molecular cloning of the recombinase activating gene 1. Biochem. Biophys. Res. Commun. 205: 687692.
10. Bingulac-Popovic, J.,, F. Figueroa,, A. Sato,, W. S. Talbot,, S. L. Johnson,, M. Gates,, J. H. Postlethwait, and, J. Klein. 1997. Mapping of mhc class I and class II regions to different linkage groups in the zebrafish, Danio rerio. Immunogenetics 46: 129134.
11. Boehm, T., and, C. C. Bleul. 2007. The evolutionary history of lymphoid organs. Nat. Immunol. 8: 131135.
12. Boehm, T., and, F. Zufall. 2006. MHC peptides and the sensory evaluation of genotype. Trends Neurosci. 29: 100107.
13. Bonneaud, C.,, J. Perez-Tris,, P. Federici,, O. Chastel, and, G. Sorci. 2006. Major histocompatibility alleles associated with local resistance to malaria in a passerine. Evolution 60: 383389.
14. Brites, D.,, S. McTaggart,, K. Morris,, J. Anderson,, K. Thomas,, I. Colson,, T. Fabbro,, T. J. Little,, D. Ebert, and, L. Du Pasquier. 2008. The Dscam homologue of the crustacean Daphnia is diversified by alternative splicing like in insects. Mol. Biol. Evol. 25: 14291439.
15. Cannon, J. P.,, R. N. Haire,, A. T. Magis,, D. D. Eason,, K. N. Winfrey,, J. A. Hernandez Prada,, K. M. Bailey,, J. Jakoncic,, G. W. Litman, and, D. A. Ostrov. 2008. A bony fish immunological receptor of the NITR multigene family mediates allogeneic recognition. Immunity 29: 228237.
16. C. elegans Sequencing Consortium. 1998. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282: 20122008.
17. Castro, L. F.,, R. F. Furlong, and, P. W. Holland. 2004. An antecedent of the MHC-linked genomic region in amphioxus. Immunogenetics 55: 782784.
18. Cooper, M. D., and, M. N. Alder. 2006. The evolution of adaptive immune systems. Cell 124: 815822.
19. Danchin, E. G.,, L. Abi-Rached,, A. Gilles, and, P. Pontarotti. 2003. Conservation of the MHC-like region throughout evolution. Immunogenetics 55: 141148.
20. Danchin, E. G., and, P. Pontarotti. 2004. Towards the reconstruction of the bilaterian ancestral pre-MHC region. Trends Genet. 20: 587591.
21. Danilova, N. and C. Amemiya. 2009. Going adaptive: the saga of antibodies. Ann. NY Acad. Sci. 1168: 130155.
22. Davis, M. M., and, P. J. Bjorkman. 1988. T-cell antigen receptor genes and T-cell recognition. Nature 334: 395402.
23. De Tomaso, A. W.,, S. V. Nyholm,, K. J. Palmeri,, K. J. Ishizuka,, W. B. Ludington,, K. Mitchel, and, I. L. Weissman. 2005. Isolation and characterization of a protochordate histocompatibility locus. Nature 438: 454459.
24. Deakin, J. E.,, H. V. Siddle,, J. G. Cross,, K. Belov, and, J. A. Graves. 2007. Class I genes have split from the MHC in the tammar wallaby. Cytogenet. Genome Res. 116: 205211.
25. Dishaw, L.,, M. Mueller,, N. Gwatney,, J. Cannon,, R. Haire,, R. Litman,, C. Amemiya,, T. Ota,, L. Rowen,, G. Glusman, and, G. Litman. 2008. Genomic complexity of the variable region-containing chitin-binding proteins in amphioxus. BMC Genet. 9: e78
26. Dong, Y.,, H. E. Taylor, and, G. Dimopoulos. 2006. AgDscam, a hypervariable immunoglobulin domain-containing receptor of the Anopheles gambiae innate immune system. PLoS Biol. 4: e229.
27. Donoghue, P. C., and, M. A. Purnell. 2005. Genome duplication, extinction and vertebrate evolution. Trends Ecol. Evol. 20: 312319.
28. Du Pasquier, L., and, B. Blomberg. 1982. The expression of antibody diversity in natural and laboratory-made polyploid individuals of the clawed toad Xenopus. Immunogenetics 15: 251260.
29. Eason, D. D.,, J. P. Cannon,, R. N. Haire,, J. P. Rast,, D. A. Ostrov, and, G. W. Litman. 2004. Mechanisms of antigen receptor evolution. Semin. Immunol. 16: 215226.
30. Flajnik, M. F. 2002. Comparative analyses of immunoglobulin genes: surprises and portents. Nat. Rev. Immunol. 2: 688698.
31. Flajnik, M. F.,, C. Canel,, J. Kramer, and, M. Kasahara. 1991. Which came first, MHC class I or class II? Immunogenetics 33: 295300.
32. Flajnik, M. F., and, L. Du Pasquier. 2004. Evolution of innate and adaptive immunity: can we draw a line? Trends Immunol. 25: 640644.
33. Flajnik, M. F., and, M. Kasahara. 2010. Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat. Rev. Genet. 11: 4759.
34. Flajnik, M. F., and, M. Kasahara. 2001. Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 15: 351362.
35. Fugmann, S. D.,, C. Messier,, L. A. Novack,, R. A. Cameron, and, J. P. Rast. 2006. An ancient evolutionary origin of the Rag1/2 gene locus. Proc. Natl. Acad. Sci. USA 103: 37283733.
36. Garcia-Fernandez, J., and, P. W. Holland. 1994. Archetypal organization of the amphioxus Hox gene cluster. Nature 370: 563566.
37. Germain, R. N.,, D. M. Bentley, and, H. Quill. 1985. Influence of allelic polymorphism on the assembly and surface expression of class II MHC (Ia) molecules. Cell 43: 233242.
38. Grimholt, U.,, F. Drablos,, S. M. Jorgensen,, B. Hoyheim, and, R. J. Stet. 2002. The major histocompatibility class I locus in Atlantic salmon (Salmo salar L.): polymorphism, linkage analysis and protein modelling. Immunogenetics 54: 570581.
39. Grimholt, U.,, S. Larsen,, R. Nordmo,, P. Midtlyng,, S. Kjoeglum,, A. Storset,, S. Saebo, and, R. J. Stet. 2003. MHC polymorphism and disease resistance in Atlantic salmon (Salmo salar); facing pathogens with single expressed major histocompatibility class I and class II loci. Immunogenetics 55: 210219.
40. Guo, P.,, M. Hirano,, B. R. Herrin,, J. Li,, C. Yu,, A. Sadlonova, and, M. D. Cooper. 2009. Dual nature of the adaptive immune system in lampreys. Nature 459: 796801.
41. Hedrick, S. M. 2004. The acquired immune system: a vantage from beneath. Immunity 21: 607615.
42. Holland, L. Z.,, R. Albalat,, K. Azumi,, E. Benito-Gutierrez,, M. J. Blow,, M. Bronner-Fraser,, F. Brunet,, T. Butts,, S. Candiani,, L. J. Dishaw,, D. E. Ferrier,, J. Garcia-Fernandez,, J. J. Gibson-Brown,, C. Gissi,, A. Godzik,, F. Hallbook,, D. Hirose,, K. Hosomichi,, T. Ikuta,, H. Inoko,, M. Kasahara,, J. Kasamatsu,, T. Kawashima,, A. Kimura,, M. Kobayashi,, Z. Kozmik,, K. Kubokawa,, V. Laudet,, G. W. Litman,, A. C. McHardy,, D. Meulemans,, M. Nonaka,, R. P. Olinski,, Z. Pancer,, L. A. Pennacchio,, M. Pestarino,, J. P. Rast,, I. Rigoutsos,, M. Robinson-Rechavi,, G. Roch,, H. Saiga,, Y. Sasakura,, M. Satake,, Y. Satou,, M. Schubert,, N. Sherwood,, T. Shiina,, N. Takatori,, J. Tello,, P. Vopalensky,, S. Wada,, A. Xu,, Y. Ye,, K. Yoshida,, F. Yoshizaki,, J. K. Yu,, Q. Zhang,, C. M. Zmasek,, P. J. de Jong,, K. Osoegawa,, N. H. Putnam,, D. S. Rokhsar,, N. Satoh, and, P. W. Holland. 2008. The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res. 18: 11001111.
43. Hsu, E.,, N. Pulham,, L. Rumfelt, and, M. Flajnik. 2006. The plasticity of immunoglobulin gene systems in evolution. Immunol. Rev. 210: 826.
44. Huang, S.,, S. Yuan,, L. Guo,, Y. Yu,, J. Li,, T. Wu,, T. Liu,, M. Yang,, K. Wu,, H. Liu,, J. Ge,, H. Huang,, M. Dong,, C. Yu,, S. Chen, and, A. Xu. 2008. Genomic analysis of the immune gene repertoire of amphioxus reveals extraordinary innate complexity and diversity. Genome Res. 18: 11121126.
45. Hurt, P.,, L. Walter,, R. Sudbrak,, S. Klages,, I. Muller,, T. Shiina,, H. Inoko,, H. Lehrach,, E. Gunther,, R. Reinhardt, and, H. Himmelbauer. 2004. The genomic sequence and comparative analysis of the rat major histocompatibility complex. Genome Res. 14: 631639.
46. Jacob, J. P.,, S. Milne,, S. Beck, and, J. Kaufman. 2000. The major and a minor class II beta-chain (B-LB) gene flank the Tapasin gene in the B-F /B-L region of the chicken major histocompatibility complex. Immunogenetics 51: 138147.
47. Janeway, C. A., Jr., and, R. Medzhitov. 2002. Innate immune recognition. Annu. Rev. Immunol. 20: 197216.
48. Joly, E.,, A. F. Le Rolle,, A. L. Gonzalez,, B. Mehling,, J. Stevens,, W. J. Coadwell,, T. Hunig,, J. C. Howard, and, G. W. Butcher. 1998. Co-evolution of rat TAP transporters and MHC class I RT1-A molecules. Curr. Biol. 8: 169172.
49. Kapitonov, V. V., and, J. Jurka. 2005. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biol. 3: e181.
50. Kasahara, M.,, J. Nakaya,, Y. Satta, and, N. Takahata. 1997. Chromosomal duplication and the emergence of the adaptive immune system. Trends Genet. 13: 9092.
51. Kasahara, M.,, T. Suzuki, and, L. Du Pasquier. 2004. On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates. Trends Immunol. 25: 105111.
52. Kasahara, M.,, Y. Watanabe,, M. Sumasu, and, T. Nagata. 2002. A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex. Proc. Natl. Acad. Sci. USA 99: 1368713692.
53. Kaufman, J. 1988. Vertebrates and the evolution of the Major Histocompatibility Complex class I and class II molecules. Verh. Dtsch. Zool. Ges. 81: 131144.
54. Kaufman, J. 1999. Co-evolving genes in MHC haplotypes: the “rule” for nonmammalian vertebrates? Immunogenetics 50: 228236.
55. Kaufman, J. 2008. The avian MHC, 161–183. In T. F. Davison,, B. Kaspers, and, K. A. Schat (eds.), The Immunology of Birds, Elsevier, Oxford.
56. Kaufman, J.,, J. Jacob,, I. Shaw,, B. Walker,, S. Milne,, S. Beck, and, J. Salomonsen. 1999. Gene organisation determines evolution of function in the chicken MHC. Immunol. Rev. 167: 101117.
57. Kaufman, J.,, S. Milne,, T. W. Gobel,, B. A. Walker,, J. P. Jacob,, C. Auffray, R. Zoorob, and, S. Beck. 1999. The chicken B locus is a minimal essential major histocompatibility complex. Nature 401: 923925.
58. Kaufman, J.,, K. Skjoedt, and, J. Salomonsen. 1990. The MHC molecules of nonmammalian vertebrates. Immunol. Rev. 113: 83117.
59. Kaufman, J.,, H. Volk, and, H. J. Wallny. 1995. A “minimal essential Mhc” and an “unrecognized Mhc”: two extremes in selection for polymorphism. Immunol. Rev. 143: 6388.
60. Kaufman, J. F.,, C. Auffray,, A. J. Korman,, D. A. Shackelford, and, J. Strominger. 1984. The class II molecules of the human and murine major histocompatibility complex. Cell 36: 113.
61. Kelley, J.,, L. Walter, and, J. Trowsdale. 2005. Comparative genomics of major histocompatibility complexes. Immunogenetics 56: 683695.
62. Li, P.,, S. T. Willie,, S. Bauer,, D. L. Morris,, T. Spies, and, R. K. Strong. 1999. Crystal structure of the MHC class I homolog MIC-A, a gamma delta T cell ligand. Immunity 10: 577584.
63. Litman, G. W.,, J. P. Cannon, and, L. J. Dishaw. 2005. Reconstructing immune phylogeny: new perspectives. Nat. Rev. Immunol. 5: 866879.
64. Litman, G. W.,, L. J. Dishaw,, J. P. Cannon,, R. N. Haire, and, J. P. Rast. 2007. Alternative mechanisms of immune receptor diversity. Curr. Opin. Immunol. 19: 526534.
65. Lobigs, M.,, A. Mullbacher,, R. V. Blanden,, G. J. Hammerling, and, F. Momburg. 1999. Antigen presentation in syrian hamster cells: substrate selectivity of TAP controlled by polymorphic residues in TAP1 and differential requirements for loading of H2 class I molecules. Immunogenetics 49: 931941.
66. Lukacs, M. F.,, H. Harstad,, U. Grimholt,, M. Beetz-Sargent,, G. A. Cooper,, L. Reid,, H. G. Bakke,, R. B. Phillips,, K. M. Miller,, W. S. Davidson, and, B. F. Koop. 2007. Genomic organization of duplicated major histocompatibility complex class I regions in Atlantic salmon (Salmo salar). BMC Genomics 8: e251.
67. Martin, A. M.,, J. K. Kulski,, C. Witt,, P. Pontarotti, and, F. T. Christiansen. 2002. Leukocyte Ig-like receptor complex (LRC) in mice and men. Trends Immunol. 23: 8188.
68. Medzhitov, R. 2009. Approaching the asymptote: 20 years later. Immunity 30: 766775.
69. Mesa, C. M.,, K. J. Thulien,, D. A. Moon,, S. M. Veniamin, and, K. E. Magor. 2004. The dominant MHC class I gene is adjacent to the polymorphic TAP2 gene in the duck, Anas platyrhynchos. Immunogenetics 56: 192203.
70. MHC Sequencing Consortium. 1999. Complete sequence and gene map of a human major histocompatibility complex. Nature 401: 921923.
71. Miller, K. M., K. H. Kaukinen, and, A. D. Schulze. 2002. Expansion and contraction of major histocompatibility complex genes: a teleostean example. Immunogenetics 53: 941963.
72. Miller, M. M.,, C. Wang,, E. Parisini,, R. D. Coletta,, R. M. Goto,, S. Y. Lee,, D. C. Barral,, M. Townes,, C. Roura-Mir,, H. L. Ford,, M. B. Brenner, and, C. C. Dascher. 2005. Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family. Proc. Natl. Acad. Sci. USA 102: 86748679.
73. Momburg, F.,, J. Roelse,, J. C. Howard,, G. W. Butcher,, G. J. Hammerling, and, J. J. Neefjes. 1994. Selectivity of MHC-encoded peptide transporters from human, mouse and rat. Nature 367: 648651.
74. Moon, D. A.,, S. M. Veniamin,, J. A. Parks-Dely, and, K. E. Magor. 2005. The MHC of the duck (Anas platyrhynchos) contains five differentially expressed class I genes. J. Immunol. 175: 67026712.
75. Moretta, A.,, C. Bottino,, M. Vitale,, D. Pende,, C. Cantoni,, M. C. Mingari,, R. Biassoni, and, L. Moretta. 2001. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu. Rev. Immunol. 19: 197223.
76. Ohno, S. 1970. Evolution by gene duplication. Springer Verlag.
77. Ohta, Y.,, W. Goetz,, M. Z. Hossain,, M. Nonaka, and, M. F. Flajnik. 2006. Ancestral organization of the MHC revealed in the amphibian Xenopus. J. Immunol. 176: 36743685.
78. Ohta, Y.,, E. C. McKinney,, M. F. Criscitiello,, and M. F. Flajnik. 2002. Proteasome, transporter associated with antigen processing, and class I genes in the nurse shark Ginglymostoma cirratum: evidence for a stable class I region and MHC haplotype lineages. J. Immunol. 168: 771781.
79. Ohta, Y.,, K. Okamura,, E. C. McKinney,, S. Bartl,, K. Hashimoto, and, M. F. Flajnik. 2000. Primitive synteny of vertebrate major histocompatibility complex class I and class II genes. Proc. Natl. Acad. Sci. USA 97: 47124717.
80. Ohta, Y.,, S. J. Powis,, R. L. Lohr,, M. Nonaka,, L. D. Pasquier, and, M. F. Flajnik. 2003. Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co-evolution among MHC class I region genes. Eur. J. Immunol. 33: 30173027.
81. Olinski, R. P.,, Lundin, L. G. &, Hallbook, F. 2006. Conserved synteny between the Ciona genome and human paralogons identifies large duplication events in the molecular evolution of the insulin-relaxin gene family. Mol. Biol. Evol. 23: 1022.
82. Pancer, Z.,, C. T. Amemiya,, G. R. Ehrhardt,, J. Ceitlin,, G. L. Gartland, and, M. D. Cooper. 2004. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 430: 174180.
83. Pancer, Z.,, W. E. Mayer,, J. Klein, and, M. D. Cooper. 2004. Prototypic T cell receptor and CD4-like coreceptor are expressed by lymphocytes in the agnathan sea lamprey. Proc. Natl. Acad. Sci. USA 101: 1327313278.
84. Parham, P. 2005. MHC class I molecules and KIRs in human history, health and survival. Nat. Rev. Immunol. 5: 201214.
85. Persson, A. C.,, R. J. Stet, and, L. Pilstrom. 1999. Characterization of MHC class I and beta(2)-microglobulin sequences in Atlantic cod reveals an unusually high number of expressed class I genes. Immunogenetics 50: 4959.
86. Putnam, N. H.,, T. Butts,, D. E. Ferrier,, R. F. Furlong,, U. Hellsten,, T. Kawashima,, M. Robinson-Rechavi,, E. Shoguchi,, A. Terry,, J. K. Yu,, E. L. Benito-Gutierrez,, I. Dubchak,, J. Garcia-Fernandez,, J. J. Gibson-Brown,, I. V. Grigoriev,, A. C. Horton,, P. J. de Jong,, J. Jurka,, V. V. Kapitonov,, Y. Kohara,, Y. Kuroki,, E. Lindquist,, S. Lucas,, K. Osoegawa,, L. A. Pennacchio,, A. A. Salamov,, Y. Satou,, T. Sauka-Spengler,, J. Schmutz,, I. T. Shin,, A. Toyoda,, M. Bronner-Fraser,, A. Fujiyama,, L. Z. Holland,, P. W. Holland,, N. Satoh, and, D. S. Rokhsar. 2008. The amphioxus genome and the evolution of the chordate karyotype. Nature 453: 10641071.
87. Rast, J. P.,, M. K. Anderson,, S. J. Strong,, C. Luer,, R. T. Litman, and, G. W. Litman. 1997. alpha, beta, gamma, and delta T cell antigen receptor genes arose early in vertebrate phylogeny. Immunity 6: 111.
88. Rast, J. P.,, L. C. Smith,, M. Loza-Coll, T. Hibino, and, G. W. Litman. 2006. Genomic insights into the immune system of the sea urchin. Science 314: 952956.
89. Rogers, S. L.,, T. W. Gobel,, B. C. Viertlboeck,, S. Milne,, S. Beck, and, J. Kaufman. 2005. Characterization of the chicken C-type lectin-like receptors B-NK and B-lec suggests that the NK complex and the MHC share a common ancestral region. J. Immunol. 174: 34753483.
90. Rogers, S. L.,, B. C. Viertlboeck,, T. W. Gobel, and, J. Kaufman. 2008. Avian NK activities, cells and receptors. Semin. Immunol. 20: 353360.
91. Sakano, H.,, K. Huppi,, G. Heinrich, and, S. Tonegawa. 1979. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature 280: 288294.
92. Salomonsen, J.,, D. Marston,, D. Avila,, N. Bumstead,, B. Johansson,, H. Juul-Madsen,, G. D. Olesen,, P. Riegert,, K. Skjodt,, O. Vainio,, M. V. Wiles, and, J. Kaufman. 2003. The properties of the single chicken MHC classical class II alpha chain (B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules. Immunogenetics 55: 605614.
93. Salomonsen, J.,, M. R. Sorensen,, D. A. Marston,, S. L. Rogers,, T. Collen,, A. van Hateren,, A. L. Smith,, R. K. Beal,, K. Skjodt, and, J. Kaufman. 2005. Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC. Proc. Natl. Acad. Sci. USA 102: 86688673.
94. Sambrook, J. G.,, F. Figueroa, and, S. Beck. 2005. A genome-wide survey of Major Histocompatibility Complex (MHC) genes and their paralogues in zebrafish. BMC Genomics 6: e152.
95. Sammut, B.,, L. Du Pasquier,, P. Ducoroy,, V. Laurens,, A. Marcuz, and, A. Tournefier. 1999. Axolotl MHC architecture and polymorphism. Eur. J. Immunol. 29: 28972907.
96. Sammut, B.,, A. Marcuz, and, L. D. Pasquier. 2002. The fate of duplicated major histocompatibility complex class Ia genes in a dodecaploid amphibian, Xenopus ruwenzoriensis. Eur. J. Immunol. 32: 15931604.
97. Schluter, S. F.,, R. M. Bernstein,, H. Bernstein, and, J. J. Marchalonis. 1999. ’Big Bang’ emergence of the combinatorial immune system. Dev. Comp. Immunol. 23: 107111.
98. Scofield, V. L.,, J. M. Schlumpberger,, L. A. West, and, I. L. Weissman. 1982. Protochordate allorecognition is controlled by a MHC-like gene system. Nature 295: 499502.
99. Siddle, H. V.,, J. E. Deakin,, P. Coggill,, E. Hart,, Y. Cheng,, E. S. Wong,, J. Harrow,, S. Beck, and, K. Belov. 2009. MHC-linked and un-linked class I genes in the wallaby. BMC Genomics 10: e310.
100. Stet, R. J.,, C. P. Kruiswijk, and, B. Dixon. 2003. Major histocompatibility lineages and immune gene function in teleost fishes: the road not taken. Crit. Rev. Immunol. 23: 441471.
101. Terado, T.,, K. Okamura,, Y. Ohta,, D. H. Shin,, S. L. Smith,, K. Hashimoto,, T. Takemoto,, M. I. Nonaka,, H. Kimura,, M. F. Flajnik, and, M. Nonaka. 2003. Molecular cloning of C4 gene and identification of the class III complement region in the shark MHC. J. Immunol. 171: 24612466.
102. Trowsdale, J., and, A. Moffett. 2008. NK receptor interactions with MHC class I molecules in pregnancy. Semin. Immunol. 20: 317320.
103. Uinuk-Ool, T.,, W. E. Mayer,, A. Sato,, R. Dongak,, M. D. Cooper, and, J. Klein. 2002. Lamprey lymphocyte-like cells express homologs of genes involved in immunologically relevant activities of mammalian lymphocytes. Proc. Natl. Acad. Sci. USA 99: 1435614361.
104. Uinuk-Ool, T. S.,, W. E. Mayer,, A. Sato,, N. Takezaki,, L. Benyon,, M. D. Cooper, and, J. Klein. 2003. Identification and characterization of a TAP-family gene in the lamprey. Immunogenetics 55: 3848.
105. Van Hateren, A.,, A. Williams,, J. Jacob,, T. Elliot, and, J. Kaufman. 2010. Co-evolution in the chicken MHC: haplotype-specific interaction of the polymorphic tapasin and dominantly-expressed class I molecules, submitted.
106. Wallny, H. J.,, D. Avila,, L. G. Hunt,, T. J. Powell,, P. Riegert,, J. Salomonsen,, K. Skjodt,, O. Vainio,, F. Vilbois,, M. V. Wiles, and, J. Kaufman. 2006. Peptide motifs of the single dominantly expressed class I molecule explain the striking MHC-determined response to Rous sarcoma virus in chickens. Proc. Natl. Acad. Sci. USA 103: 14341439.
107. Watson, F. L.,, R. Puttmann-Holgado, F. Thomas,, D. L. Lamar,, M. Hughes,, M. Kondo,, V. I. Rebel, and, D. Schmucker. 2005. Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science 309: 18741878.
108. Wegner, K. M.,, M. Kalbe,, J. Kurtz,, T. B. Reusch, and, M. Milinski. 2003. Parasite selection for immunogenetic optimality. Science 301: 1343.
109. Westerdahl, H.,, J. Waldenstrom,, B. Hansson,, D. Hasselquist,, T. von Schantz, and, S. Bensch. 2005. Associations between malaria and MHC genes in a migratory songbird. Proc. Biol. Sci. 272: 15111518.
110. Westerdahl, H.,, H. Wittzell, and, T. von Schantz. 2000. Mhc diversity in two passerine birds: no evidence for a minimal essential Mhc. Immunogenetics 52: 92100.
111. Wilson, I. A., and, P. J. Bjorkman. 1998. Unusual MHC-like molecules: CD1, Fc receptor, the hemochromatosis gene product, and viral homologs. Curr. Opin. Immunol. 10: 6773.
112. Yu, C.,, G. R. Ehrhardt,, M. N. Alder,, M. D. Cooper, and, A. Xu. 2009. Inhibitory signaling potential of a TCR-like molecule in lamprey. Eur. J. Immunol. 39: 571579.
113. Zhang, S. M.,, C. M. Adema,, T. B. Kepler, and, E. S. Loker. 2004. Diversification of Ig superfamily genes in an invertebrate. Science 305: 251254.
114. Zhu, X.,, X. Zhao,, W. F. Burkholder,, A. Gragerov,, C. M. Ogata,, M. E. Gottesman, and, W. A. Hendrickson. 1996. Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272: 16061614.
115. Zucchetti, I.,, R. De Santis,, S. Grusea,, P. Pontarotti, and, L. Du Pasquier. 2009. Origin and evolution of the vertebrate leukocyte receptors: the lesson from tunicates. Immunogenetics 61: 463481.

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