Immunogenetics

, Volume 65, Issue 4, pp 299–311 | Cite as

In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function

  • Elna Follin
  • Maria Karlsson
  • Claus Lundegaard
  • Morten Nielsen
  • Stefan Wallin
  • Kajsa Paulsson
  • Helena Westerdahl
Original Paper

Abstract

The major histocompatibility complex (MHC) genes are the most polymorphic genes found in the vertebrate genome, and they encode proteins that play an essential role in the adaptive immune response. Many songbirds (passerines) have been shown to have a large number of transcribed MHC class I genes compared to most mammals. To elucidate the reason for this large number of genes, we compared 14 MHC class I alleles (α1–α3 domains), from great reed warbler, house sparrow and tree sparrow, via phylogenetic analysis, homology modelling and in silico peptide-binding predictions to investigate their functional and genetic relationships. We found more pronounced clustering of the MHC class I allomorphs (allele specific proteins) in regards to their function (peptide-binding specificities) compared to their genetic relationships (amino acid sequences), indicating that the high number of alleles is of functional significance. The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged 10 million years ago (MYA), had overlapping peptide-binding specificities, and these similarities across species were also confirmed in phylogenetic analyses based on amino acid sequences. Notably, there were also overlapping peptide-binding specificities in the allomorphs from house sparrow and great reed warbler, although these species diverged 30 MYA. This overlap was not found in a tree based on amino acid sequences. Our interpretation is that convergent evolution on the level of the protein function, possibly driven by selection from shared pathogens, has resulted in allomorphs with similar peptide-binding repertoires, although trans-species evolution in combination with gene conversion cannot be ruled out.

Keywords

Major histocompatibility complex (MHC) class I Functional clustering Convergent evolution Trans-species evolution Gene conversion Passerine birds 

Supplementary material

251_2012_676_MOESM1_ESM.pdf (215 kb)
ESM 1(PDF 215 kb)
251_2012_676_Fig6_ESM.jpg (3.4 mb)
ESM 2

(JPEG 3506 kb)

251_2012_676_MOESM2_ESM.eps (1.6 mb)
High resolution image (EPS 1652 kb)

References

  1. Aguilar A, Edwards SV, Smith TB, Wayne RK (2006) Patterns of variation in MHC class II beta loci of the little greenbul (Andropadus virens) with comments on MHC evolution in birds. J Hered 97:133–142PubMedCrossRefGoogle Scholar
  2. Apanius V, Penn D, Slev PR, Ruff LR, Potts WK (1997) The nature of selection on the major histocompatibility complex. Crit Rev Immunol 17:179–224PubMedCrossRefGoogle Scholar
  3. Axelsson-Robertson R, Ahmed RK, Weichold FF, Ehlers MM, Kock MM, Sizemore D, Sadoff J, Maeurer M (2011) Human leukocyte antigens A*3001 and A*3002 show distinct peptide-binding patterns of the Mycobacterium tuberculosis protein TB10.4: consequences for immune recognition. Clin vaccine immunol CVI 18:125–134CrossRefGoogle Scholar
  4. Balakrishnan CN, Ekblom R, Volker M, Westerdahl H, Godinez R, Kotkiewicz H, Burt DW, Graves T, Griffin DK, Warren WC, Edwards SV (2010) Gene duplication and fragmentation in the zebra finch major histocompatibility complex. BMC Biol 8:29PubMedCrossRefGoogle Scholar
  5. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329:512–518PubMedCrossRefGoogle Scholar
  6. Bollmer JL, Dunn PO, Whittingham LA, Wimpee C (2010) Extensive MHC class II B gene duplication in a passerine, the common Yellowthroat (Geothlypis trichas). J Hered 101:448–460PubMedCrossRefGoogle Scholar
  7. Bonneaud C, Sorci G, Morin V, Westerdahl H, Zoorob R, Wittzell H (2004) Diversity of MHC class I and IIB genes in house sparrows (Passer domesticus). Immunogenetics 55:855–865PubMedCrossRefGoogle Scholar
  8. Borghans JA, Noest AJ, De Boer RJ (2003) Thymic selection does not limit the individual MHC diversity. Eur J Immunol 33:3353–3358PubMedCrossRefGoogle Scholar
  9. Bos DH, Waldman B (2006) Evolution by recombination and transspecies polymorphism in the MHC class I gene of Xenopus laevis. Mol Biol Evol 23:137–143PubMedCrossRefGoogle Scholar
  10. Brown JW, Rest JS, Garcia-Moreno J, Sorenson MD, Mindell DP (2008) Strong mitochondrial DNA support for a Cretaceous origin of modern avian lineages. BMC Biol 6:6PubMedCrossRefGoogle Scholar
  11. Chaves LD, Krueth SB, Reed KM (2009) Defining the turkey MHC: sequence and genes of the B locus. J Immunol 183:6530–6537PubMedCrossRefGoogle Scholar
  12. Cramp S (1992) Handbook of the birds of Europe, the Middle East and North Africa. Oxford University Press, OxfordGoogle Scholar
  13. Ekblom R, Stapley J, Ball AD, Birkhead T, Burke T, Slate J (2011) Genetic mapping of the major histocompatibility complex in the zebra finch (Taeniopygia guttata). Immunogenetics 63:523–530PubMedCrossRefGoogle Scholar
  14. Erup Larsen M, Kloverpris H, Stryhn A, Koofhethile CK, Sims S, Ndung'u T, Goulder P, Buus S, Nielsen M (2011) HLA restrictor—a tool for patient-specific predictions of HLA restriction elements and optimal epitopes within peptides. Immunogenetics 63:43–55PubMedCrossRefGoogle Scholar
  15. Guillemot F, Billault A, Pourquie O, Behar G, Chausse AM, Zoorob R, Kreibich G, Auffray C (1988) A molecular map of the chicken major histocompatibility complex: the class II beta genes are closely linked to the class I genes and the nucleolar organizer. EMBO J 7:2775–2785PubMedGoogle Scholar
  16. Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98Google Scholar
  17. Hee CS, Gao S, Loll B, Miller MM, Uchanska-Ziegler B, Daumke O, Ziegler A (2010) Structure of a classical MHC class I molecule that binds "non-classical" ligands. PLoS Biol 8:e1000557PubMedCrossRefGoogle Scholar
  18. Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM (1991) Common west African HLA antigens are associated with protection from severe malaria. Nature 352:595–600PubMedCrossRefGoogle Scholar
  19. Hoof I, Peters B, Sidney J, Pedersen LE, Sette A, Lund O, Buus S, Nielsen M (2009) NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics 61:1–13PubMedCrossRefGoogle Scholar
  20. Karosiene E, Lundegaard C, Lund O, Nielsen M (2012) NetMHCcons: a consensus method for the major histocompatibility complex class I predictions. Immunogenetics 64:177–186PubMedCrossRefGoogle Scholar
  21. Katoh K, Misawa K, Kuma K, Miyata T (2002) MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30:3059–3066PubMedCrossRefGoogle Scholar
  22. Kaufman J (1999) Co-evolving genes in MHC haplotypes: the "rule" for nonmammalian vertebrates? Immunogenetics 50:228–236PubMedCrossRefGoogle Scholar
  23. Kaufman J, Milne S, Gobel TW, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999) The chicken B locus is a minimal essential major histocompatibility complex. Nature 401:923–925PubMedCrossRefGoogle Scholar
  24. Kaufman J, Volk H, Wallny HJ (1995) A "minimal essential MHC" and an "unrecognized MHC": two extremes in selection for polymorphism. Immunol Rev 143:63–88PubMedCrossRefGoogle Scholar
  25. Koch M, Camp S, Collen T, Avila D, Salomonsen J, Wallny HJ, van Hateren A, Hunt L, Jacob JP, Johnston F, Marston DA, Shaw I, Dunbar PR, Cerundolo V, Jones EY, Kaufman J (2007) Structures of an MHC class I molecule from B21 chickens illustrate promiscuous peptide binding. Immunity 27:885–899PubMedCrossRefGoogle Scholar
  26. Loiseau C, Zoorob R, Robert A, Chastel O, Julliard R, Sorci G (2011) Plasmodium relictum infection and MHC diversity in the house sparrow (Passer domesticus). Proc Biol Sci Roy Soc 278:1264–1272CrossRefGoogle Scholar
  27. Lundegaard C, Lamberth K, Harndahl M, Buus S, Lund O, Nielsen M (2008) NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8–11. Nucleic Acids Res 36:W509–W512PubMedCrossRefGoogle Scholar
  28. Lundegaard C, Lund O, Buus S, Nielsen M (2010) Major histocompatibility complex class I binding predictions as a tool in epitope discovery. Immunology 130:309–318PubMedCrossRefGoogle Scholar
  29. Miller HC, Lambert DM (2004) Gene duplication and gene conversion in class II MHC genes of New Zealand robins (Petroicidae). Immunogenetics 56:178–191PubMedGoogle Scholar
  30. Neefjes J, Jongsma ML, Paul P, Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11:823–836PubMedGoogle Scholar
  31. Nene V, Svitek N, Toye P, Golde WT, Barlow J, Harndahl M, Buus S, Nielsen M (2012) Designing bovine T cell vaccines via reverse immunology. Ticks Tick-Borne Dis 3:188–192PubMedCrossRefGoogle Scholar
  32. Nielsen M, Lund O, Lundegaard C (2012) MHCcluster, a method for functional clustering of MHC molecules. ISCB-LatinGoogle Scholar
  33. Nielsen M, Lundegaard C, Blicher T, Lamberth K, Harndahl M, Justesen S, Roder G, Peters B, Sette A, Lund O, Buus S (2007) NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence. PLoS One 2:e796PubMedCrossRefGoogle Scholar
  34. Nielsen M, Lundegaard C, Lund O, Petersen TN (2010) CPHmodels-3.0—remote homology modeling using structure-guided sequence profiles. Nucleic Acids Res 38:W576–W581PubMedCrossRefGoogle Scholar
  35. Nowak MA, Tarczyhornoch K, Austyn JM (1992) The optimal number of major histocompatibility complex—molecules in an individual. Proc Natl Acad Sci USA 89:10896–10899PubMedCrossRefGoogle Scholar
  36. Pedersen LE, Harndahl M, Rasmussen M, Lamberth K, Golde WT, Lund O, Nielsen M, Buus S (2011) Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities. Immunogenetics 63:821–834PubMedCrossRefGoogle Scholar
  37. Promerova M, Albrecht T, Bryja J (2009) Extremely high MHC class I variation in a population of a long-distance migrant, the Scarlet Rosefinch (Carpodacus erythrinus). Immunogenetics 61:451–461PubMedCrossRefGoogle Scholar
  38. Promerova M, Babik W, Bryja J, Albrecht T, Stuglik M, Radwan J (2012) Evaluation of two approaches to genotyping major histocompatibility complex class I in a passerine-CE-SSCP and 454 pyrosequencing. Mol Ecol Resour 12:285–292PubMedCrossRefGoogle Scholar
  39. Prugnolle F, Manica A, Charpentier M, Guegan JF, Guernier V, Balloux F (2005) Pathogen-driven selection and worldwide HLA class I diversity. Curr Biol CB 15:1022–1027CrossRefGoogle Scholar
  40. Rammensee HG, Friede T, Stevanoviic S (1995) MHC ligands and peptide motifs: first listing. Immunogenetics 41:178–228PubMedCrossRefGoogle Scholar
  41. Reed KM, Bauer MM, Monson MS, Benoit B, Chaves LD, O'Hare TH, Delany ME (2011) Defining the turkey MHC: identification of expressed class I- and class IIB-like genes independent of the MHC-B. Immunogenetics 63:753–771PubMedCrossRefGoogle Scholar
  42. Sato A, Mayer WE, Tichy H, Grant PR, Grant BR, Klein J (2001) Evolution of MHC class II B genes in Darwin's finches and their closest relatives: birth of a new gene. Immunogenetics 53:792–801PubMedCrossRefGoogle Scholar
  43. Schut E, Aguilar JR, Merino S, Magrath MJ, Komdeur J, Westerdahl H (2011) Characterization of MHC-I in the blue tit (Cyanistes caeruleus) reveals low levels of genetic diversity and trans-population evolution across European populations. Immunogenetics 63:531–542PubMedCrossRefGoogle Scholar
  44. Sepil I, Moghadam HK, Huchard E, Sheldon BC (2012) Characterization and 454 pyrosequencing of Major Histocompatibility Complex class I genes in the great tit reveal complexity in a passerine system. BMC Evol Biol 12:68PubMedCrossRefGoogle Scholar
  45. Shaw I, Powell TJ, Marston DA, Baker K, van Hateren A, Riegert P, Wiles MV, Milne S, Beck S, Kaufman J (2007) Different evolutionary histories of the two classical class I genes BF1 and BF2 illustrate drift and selection within the stable MHC haplotypes of chickens. J Immunol 178:5744–5752PubMedGoogle Scholar
  46. Shiina T, Shimizu S, Hosomichi K, Kohara S, Watanabe S, Hanzawa K, Beck S, Kulski JK, Inoko H (2004) Comparative genomic analysis of two avian (quail and chicken) MHC regions. J Immunol 172:6751–6763PubMedGoogle Scholar
  47. Sibly RM, Witt CC, Wright NA, Venditti C, Jetz W, Brown JH (2012) Energetics, lifestyle, and reproduction in birds. Proc Natl Acad Sci USA 109:10937–10941PubMedCrossRefGoogle Scholar
  48. Stamatakis A, Hoover P, Rougemont J (2008) A rapid bootstrap algorithm for the RAxML Web servers. Syst Biol 57:758–771PubMedCrossRefGoogle Scholar
  49. Stearns SC, Koella JC (2007) Evolution in health and disease. Oxford University Press, New YorkGoogle Scholar
  50. Strandh M, Lannefors M, Bonadonna F, Westerdahl H (2011) Characterization of MHC class I and II genes in a subantarctic seabird, the blue petrel, Halobaena caerulea (Procellariiformes). Immunogenetics 63:653–666PubMedCrossRefGoogle Scholar
  51. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739PubMedCrossRefGoogle Scholar
  52. Thomsen MC, Nielsen M (2012) Seq2Logo: a method for construction and visualization of amino acid binding motifs and sequence profiles including sequence weighting, pseudo counts and two-sided representation of amino acid enrichment and depletion. Nucleic acids resGoogle Scholar
  53. Walker BA, Hunt LG, Sowa AK, Skjodt K, Gobel TW, Lehner PJ, Kaufman J (2011) The dominantly expressed class I molecule of the chicken MHC is explained by coevolution with the polymorphic peptide transporter (TAP) genes. Proc Natl Acad Sci USA 108:8396–8401PubMedCrossRefGoogle Scholar
  54. Walker BA, van Hateren A, Milne S, Beck S, Kaufman J (2005) Chicken TAP genes differ from their human orthologues in locus organisation, size, sequence features and polymorphism. Immunogenetics 57:232–247PubMedCrossRefGoogle Scholar
  55. Wallny HJ, Avila D, Hunt LG, Powell TJ, Riegert P, Salomonsen J, Skjodt K, Vainio O, Vilbois F, Wiles MV, Kaufman J (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 103:1434–1439PubMedCrossRefGoogle Scholar
  56. Warren WC, Clayton DF, Ellegren H, Arnold AP, Hillier LW, Kunstner A, Searle S, White S, Vilella AJ, Fairley S, Heger A, Kong L, Ponting CP, Jarvis ED, Mello CV, Minx P, Lovell P, Velho TA, Ferris M, Balakrishnan CN, Sinha S, Blatti C, London SE, Li Y, Lin YC, George J, Sweedler J, Southey B, Gunaratne P, Watson M, Nam K, Backstrom N, Smeds L, Nabholz B, Itoh Y, Whitney O, Pfenning AR, Howard J, Volker M, Skinner BM, Griffin DK, Ye L, McLaren WM, Flicek P, Quesada V, Velasco G, Lopez-Otin C, Puente XS, Olender T, Lancet D, Smit AF, Hubley R, Konkel MK, Walker JA, Batzer MA, Gu W, Pollock DD, Chen L, Cheng Z, Eichler EE, Stapley J, Slate J, Ekblom R, Birkhead T, Burke T, Burt D, Scharff C, Adam I, Richard H, Sultan M, Soldatov A, Lehrach H, Edwards SV, Yang SP, Li X, Graves T, Fulton L, Nelson J, Chinwalla A, Hou S, Mardis ER, Wilson RK (2010) The genome of a songbird. Nature 464:757–762PubMedCrossRefGoogle Scholar
  57. Wegner KM, Kalbe M, Kurtz J, Reusch TBH, Milinski M (2003) Parasite selection for immunogenetic optimality. Science 301:1343PubMedCrossRefGoogle Scholar
  58. Westerdahl H (2007) Passerine MHC: genetic variation and disease resistance in the wild. J Ornithol 148:S469–S477CrossRefGoogle Scholar
  59. Westerdahl H, Wittzell H, von Schantz T (1999) Polymorphism and transcription of Mhc class I genes in a passerine bird, the great reed warbler. Immunogenetics 49:158–170PubMedCrossRefGoogle Scholar
  60. Westerdahl H, Wittzell H, von Schantz T (2000) Mhc diversity in two passerine birds: no evidence for a minimal essential Mhc. Immunogenetics 52:92–100PubMedCrossRefGoogle Scholar
  61. Wittzell H, Madsen T, Westerdahl H, Shine R, von Schantz T (1998) MHC variation in birds and reptiles. Genetica 104:301–309PubMedCrossRefGoogle Scholar
  62. Yang Z (1997) PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci CABIOS 13:555–556Google Scholar
  63. Yang Z (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24:1586–1591PubMedCrossRefGoogle Scholar
  64. Yang Z, Bielawski JP (2000) Statistical methods for detecting molecular adaptation. Trends Ecol Evol 15:496–503PubMedCrossRefGoogle Scholar
  65. Yang Z, Wong WS, Nielsen R (2005) Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 22:1107–1118PubMedCrossRefGoogle Scholar
  66. Zagalska-Neubauer M, Babik W, Stuglik M, Gustafsson L, Cichon M, Radwan J (2010) 454 sequencing reveals extreme complexity of the class II Major Histocompatibility Complex in the collared flycatcher. BMC Evol Biol 10:395PubMedCrossRefGoogle Scholar
  67. Zehtindjiev P, Ilieva M, Westerdahl H, Hansson B, Valkiunas G, Bensch S (2008) Dynamics of parasitemia of malaria parasites in a naturally and experimentally infected migratory songbird, the great reed warbler Acrocephalus arundinaceus. Exp Parasitol 119:99–110PubMedCrossRefGoogle Scholar
  68. Zhang H, Lund O, Nielsen M (2009) The PickPocket method for predicting binding specificities for receptors based on receptor pocket similarities: application to MHC-peptide binding. Bioinformatics 25:1293–1299PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Elna Follin
    • 1
  • Maria Karlsson
    • 2
  • Claus Lundegaard
    • 3
  • Morten Nielsen
    • 3
  • Stefan Wallin
    • 4
  • Kajsa Paulsson
    • 1
  • Helena Westerdahl
    • 2
  1. 1.Immunology Section, BMC-D14, Department of Experimental Medical SciencesLund UniversityLundSweden
  2. 2.Molecular Ecology and Evolution Laboratory, Department of BiologyLund UniversityLundSweden
  3. 3.Center for Biological Sequence Analysis, DTULyngbyDenmark
  4. 4.Computational Biology and Biological PhysicsLund UniversityLundSweden

Personalised recommendations