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Characterization of MHC class I in a long-distance migrant shorebird suggests multiple transcribed genes and intergenic recombination

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Abstract

The major histocompatibility complex (MHC) includes highly polymorphic gene families encoding proteins crucial to the vertebrate acquired immune system. Classical MHC class I (MHCI) genes code for molecules expressed on the surfaces of most nucleated cells and are associated with defense against intracellular pathogens, such as viruses. These genes have been studied in a few wild bird species, but have not been studied in long-distance migrating shorebirds. Red Knots Calidris canutus are medium-sized, monogamous sandpipers with migratory routes that span the globe. Understanding how such long-distance migrants protect themselves from disease has gained new relevance since the emergence of avian-borne diseases, including intracellular pathogens recognized by MHCI molecules, such as avian influenza. In this study, we characterized MHCI genes in knots and found 36 alleles in eight individuals and evidence for six putatively functional and expressed MHCI genes in a single bird. We also found evidence for recombination and for positive selection at putative peptide binding sites in exons 2 and 3. These results suggest surprisingly high MHC diversity in knots, given their demographic history. This may be a result of selection from diverse pathogens encountered by shorebirds throughout their annual migrations.

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References

  • Afanassieff M, Goto RM, Ha J, Sherman MA, Zhong L, Auffray C, Coudert F, Zoorob R, Miller MM (2001) At least one class I gene in restriction fragment pattern-Y (Rfp-Y), the second MHC gene cluster in the chicken, is transcribed, polymorphic, and shows divergent specialization in antigen binding region. J Immunol 166:3324–3333

    PubMed  CAS  Google Scholar 

  • Alcaide M, Edwards SV, Cadahía L, Negro JJ (2009) MHC class I genes of birds of prey: isolation, polymorphism and diversifying selection. Cons Gen 10:1349–1355

    Article  CAS  Google Scholar 

  • Altizer S, Bartel R, Han BA (2011) Animal migration and infectious disease risk. Science 331:296–302

    Article  PubMed  CAS  Google Scholar 

  • Baker AJ, Pereira SL, Paton TA (2007) Phylogenetic relationships and divergence times of Charadriiformes genera: multigene evidence for the Cretaceous origin of at least 14 clades of shorebirds. Biol Lett 3:205–209

    Article  PubMed  Google Scholar 

  • Balakrishnan CN, Ekblom R, Völker 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 8:29. doi:10.1186/1741-7007-8-29

    Article  PubMed  Google Scholar 

  • Betts M, Russell R (2003) Amino acid properties and consequences of substitutions. In: Barnes M, Gray I (eds) Bioinformatics for geneticists. Wiley, Chichester, pp 289–316

    Chapter  Google Scholar 

  • Bjorkman P, Saper M, Samraoui B, Bennett W, Strominger J, Wiley D (1987) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329:512–518

    Article  PubMed  CAS  Google Scholar 

  • Bjorkman PJ, Parham P (1990) Structure, function, and diversity of class I major histocompatibility complex molecules. Ann Rev Biochem 59:253–388

    Article  PubMed  CAS  Google Scholar 

  • 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 55:855–865

    Article  PubMed  CAS  Google Scholar 

  • Brown JD, Luttrell MP, Berghaus RD, Kistler W, Keeler SP, Howey A, Wilcox B, Hall J, Niles L, Dey A, Knutsen G, Fritz K, Stallknecht DE (2010) Prevalence of antibodies to type A influenza virus in wild avian species using two serologic assays. J Wildlife Dis 46:896–911

    Google Scholar 

  • Buehler, D. M. (2003) Phylogeography and genetic diversity in Red Knots (Calidris canutus). MSc Thesis. Department of Zoology. Department of Zoology. University of Toronto, Toronto.

  • Buehler DM, Baker AJ (2005) Population divergence times and historical demography in Red Knots and Dunlins. Condor 107:497–513

    Article  Google Scholar 

  • Buehler DM, Baker AJ, Piersma T (2006) Reconstructing palaeoflyways of the late Pleistocene and early Holocene Red Knot (Calidris canutus). Ardea 94:485–498

    Google Scholar 

  • Buehler DM, Piersma T (2008) Travelling on a budget: predictions and ecological evidence for bottlenecks in the annual cycle of long-distance migrants. Phil Trans R Soc Lond B 363:247–266

    Article  Google Scholar 

  • Buehler DM, Tieleman BI, Piersma T (2010) How do migrant species stay healthy over the annual cycle? A conceptual model for immune function and disease resistance. Int Comp Biol 50:346–357

    Article  Google Scholar 

  • Cheng Y, Stuart A, Morris K, Taylor R, Siddle HV, Deakin JE, Jones M, Amemiya CT, Belov K (2012) Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC. BMC Genomics 13:87

    Article  PubMed  CAS  Google Scholar 

  • Cloutier A, Mills J, Baker A (2011) Characterization and locus-specific typing of MHC class I genes in the red-billed gull (Larus scopulinus) provides evidence for major, minor, and nonclassical loci. Immunogenetics. doi:10.1007/s00251-011-0516-x

  • Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA (2005) Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol Rev 207:145–157

    Article  PubMed  CAS  Google Scholar 

  • Dean A, Greenwald J (1995) Use of filtered pipet tips to elute DNA from agarose gels. Biotechniques 18:980

    PubMed  CAS  Google Scholar 

  • Drummond, A. J., Ashton, B., Buxton, S., Cheung, M., Cooper, A., Duran, C., Field, M., Heled, J., Kearse, M., Markowitz, S., Moir, R., Stones-Havas, S., Sturrock, S., Thierer, T., and Wilson, A. (2011) Geneious v5.4. http://www.geneious.com, pp. Available from www.geneious.com.

  • Eimes J, Bollmer J, Whittingham L, Johnson J, Van Oosterhout C, Dunn P (2011) Rapid loss of MHC class II variation in a bottlenecked population is explained by drift and loss of copy number variation. J Evol Biol. doi:10.1111/j.1420-9101.2011.02311.x

  • Grossberger D, Parham P (1992) Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure. Immunogenetics 36:166–174

    Article  PubMed  CAS  Google Scholar 

  • Hanson BA, Luttrell MP, Goekjian VH, Niles L, Swayne DE, Senne DA, Stallknecht DE (2008) Is the occurrence of avian influenza virus in Charadriiformes species and location dependent? J Wildlife Dis 44:351–361

    CAS  Google Scholar 

  • Hunt HD, Goto RM, Foster DN, Bacon LD, Miller MM (2006) At least one YMHCI molecule in the chicken is alloimmunogenic and dynamically expressed on spleen cells during development. Immunogenetics 58:297–307

    Article  PubMed  CAS  Google Scholar 

  • Huson DH, Bryant D (2006) Application of phylogenetic networks in evolutionary studies. Mol Biol Evol 23:254–267

    Article  PubMed  CAS  Google Scholar 

  • Jarvi S, Goto R, Gee G, Briles W, Miller M (1999) Identification, inheritance, and linkage of B-G-like and MHC class I genes in cranes. J Heredity 90:152–159

    Article  CAS  Google Scholar 

  • Kaufman J (2008) The Avian MHC. In: Davison F, Kaspars B, Schat KA (eds) Avian immunology. Elsevier, London, San Diego, pp 323–338

    Google Scholar 

  • Kaufman J, Milne S, Göbel TW, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999) The chicken B locus is a minimal essential major histocompatibility complex. Nature 401:923–925

    Article  PubMed  CAS  Google Scholar 

  • Kaufman J, Salomonsen J, Flajnik M (1994) Evolutionary conservation of MHC class I and class II molecules—different yet the same. Seminars Immunol 6:411–424

    Article  CAS  Google Scholar 

  • Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695

    Article  PubMed  CAS  Google Scholar 

  • Klein J (1986) Natural history of the major histocompatibility complex. Wiley, New York

    Google Scholar 

  • Klein J, Bontrop RE, Dawkins RL, Erlich HA, Gyllensten UB, Heise ER, Jones PP, Parham P, Wakeland EK, Watkins DI (1990) Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics 31:217–219

    PubMed  CAS  Google Scholar 

  • Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SDW (2006) GARD: a genetic algorithm for recombination detection. Bioinformatics 22:3096–3098

    Article  PubMed  Google Scholar 

  • Krauss S, Obert CA, Franks J, Walker D, Jones K, Seiler P, Niles L, Pryor SP, Obenauer JC, Naeve CW, Widjaja L, Webby RJ, Webster RG (2007) Influenza in migratory birds and evidence of limited intercontinental virus exchange. PLoS Pathogens 3:e167

    Article  PubMed  Google Scholar 

  • Kryazhimskiy S, Plotkin JB (2008) The population genetics of d N /d S . PLoS Genetics 4:e1000304

    Article  PubMed  Google Scholar 

  • Møller AP, Erritzøe J (1998) Host immune defence and migration in birds. Evol Ecol 12:945–953

    Article  Google Scholar 

  • Moon DA, Veniamin SM, Parks-Dely JA, Magor KE (2005) The MHC of the duck (Anas platyrhynchos) contains five differentially expressed class I genes. J Immunol 175:6702–6712

    PubMed  CAS  Google Scholar 

  • Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods 5:621–628

    Article  PubMed  CAS  Google Scholar 

  • Murphy K, Travers P, Walport M (2008) Janeway’s immunobiology, 7th edn. Garland Science, New York

    Google Scholar 

  • Nei M, Gu X, Sitnikova T (1997) Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci USA 94:7799–7806

    Article  PubMed  CAS  Google Scholar 

  • Piersma T (1997) Do global patterns of habitat use and migration strategies co-evolve with relative investments in immunocompetence due to spatial variation in parasite pressure? Oikos 80:623–631

    Article  Google Scholar 

  • Piersma T (2006) Understanding the numbers and distributions of waders and other animals in a changing world: habitat choice as the lock and the key. Stilt 50:3–14

    Google Scholar 

  • Piersma T (2007) Using the power of comparison to explain habitat use and migration strategies of shorebirds worldwide. J Ornithol 148(Suppl 1):S45–S59

    Article  Google Scholar 

  • Piersma T, Baker AJ (2000) Life history characteristics and the conservation of migratory shorebirds. In: Gosling LM, Sutherland WJ (eds) Behaviour and Conservation. Cambridge University Press, Cambridge, UK, pp 105–124

    Google Scholar 

  • Piersma T, Davidson NC (1992) The migrations and annual cycles of five subspecies of knots in perspective. Wader Study Group Bull 64(Suppl):187–197

    Google Scholar 

  • Piertney SB, Oliver MK (2006) The evolutionary ecology of the major histocompatibility complex. Heredity 96:7–21

    PubMed  CAS  Google Scholar 

  • Piontkivska H, Nei M (2003) Birth-and-death evolution in primate MHC class I genes: divergence time estimates. Mol Biol Evol 20:601–609

    Article  PubMed  CAS  Google Scholar 

  • Posada D (2008) jModelTest: phylogenetic model averaging. Mol Biol Evol 25:1253–1256

    Article  PubMed  CAS  Google Scholar 

  • Potter CJ, Luo L (2010) Splinkerette PCR for mapping transposable elements in Drosophila. PLoS One 5(10168). doi:10.1371/journal.pone.0010168

  • Promerová 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 61:451–461

    Article  PubMed  Google Scholar 

  • Reed KM, Bauer MM, Monson MS, Benoit B, Chaves LD, O’Hare TH, Delany ME (2012) Defining the Turkey MHC: identification of expressed class I- and class IIB-like genes independent of the MHC-B. Immunogenetics 63:753–771

    Article  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  • Sambrook J, Russell DW (2001) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

    Google Scholar 

  • Saper M, Bjorkman P, Wiley D (1991) Refined structure of the human histocompatibility antigen HLA-A2 at 2.6Å resolution. J Mol Biol 219:277–319

    Article  PubMed  CAS  Google Scholar 

  • Schut E, Aguilar J, Merino S, Magrath M, 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 63:531–542

    Article  PubMed  Google Scholar 

  • 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 12:68

    Article  PubMed  CAS  Google Scholar 

  • Shiina T, Hosomichi K, Hanzawa K (2006) Comparative genomics of the poultry major histocompatibility complex. Anim Sci Journal 77:151–162

    Article  CAS  Google Scholar 

  • Sommer S (2005) The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Frontiers Zool 2:16. doi:10.1186/1742-9994-2-16

    Article  Google Scholar 

  • Spurgin LG, Oosterhout CV, Illera JC, Bridgett S, Gharbi K, Emerson BC, Richardson DS (2011) Gene conversion rapidly generates major histocompatibility complex diversity in recently founded bird populations. Mol Ecol 20:5213–5225

    Article  PubMed  CAS  Google Scholar 

  • Spurgin LG, Richardson DS (2010) How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc R Soc Lond B 277:979–988

    Article  CAS  Google Scholar 

  • Strand T, Westerdahl H, Höglund J, Alatalo RV, Siitari H (2007) The Mhc class II of the Black grouse (Tetrao tetrix) consists of low numbers of B and Y genes with variable diversity and expression. Immunogenetics 59:725–734

    Article  PubMed  CAS  Google Scholar 

  • 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 63:653–666

    Article  PubMed  CAS  Google Scholar 

  • Stroynowski I, Lindahl KF (1994) Antigen presentation by non-classical class I molecules. Current Opin Immunol 6:38–44

    Article  CAS  Google Scholar 

  • 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 28:2731–2739

    Article  PubMed  CAS  Google Scholar 

  • Thomas G, Reynolds JD (2007) Sexual conflict and the evolution of breeding systems in shorebirds. Advances Study Behav 37:279–342

    Article  Google Scholar 

  • Verkuil YI, Piersma T, Jukema J, Hooljmeijer JCEW, Zwarts L, Baker AJ (2012) The interplay between habitat availability and population differentiation: a case study on genetic and morphological structure in an inland wader (Charadriiformes). Biol J Linnean Soc 106:641–656

    Article  Google Scholar 

  • Westerdahl H (2007) Passerine MHC: genetic variation and disease resistance in the wild. J Ornithol 148:s469–s477

    Google Scholar 

  • 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 49:158–170

    Article  PubMed  CAS  Google Scholar 

  • Westerdahl H, Wittzell H, von Schantz T (2000) Mhc diversity in two passerine birds: no evidence for a minimal essential Mhc. Immunogenetics 52:92–100

    Article  PubMed  CAS  Google Scholar 

  • Wittzell H, Schantz T, Zoorob R, Auffray C (1995) Rfp-Y-like sequences assort independently of pheasant Mhc genes. Immunogenetics 42:68–71

    Article  PubMed  CAS  Google Scholar 

  • Xia C, Hu T, Yang T, Wang L, Xu G, Lin C (2005) cDNA cloning, genomic structure and expression analysis of the goose (Anser cygnoides) MHC class I gene. Vet Immunol Immunopathol 107:291–302

    Article  PubMed  CAS  Google Scholar 

  • Yang Z (2007) PAML 4: a program package for phylogenetic analysis by maximum likelihood. Mol Biol Evol 24:1586–1591

    Article  PubMed  CAS  Google Scholar 

  • Yang Z, Wong WSW, Nielsen R (2005) Bayes empirical Bayes inference of amino acid sites under positive selection. Mol Biol Evol 22:1107–1118

    Google Scholar 

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Acknowledgments

We thank Alberto Castillo and Rosemary Gibson for valuable help in the lab; Oliver Haddrath for technical support in the lab and stimulating discussion; Sergio Pereira for help with RNAseq; Sue Chopra, Cathy Dutton, Kirsten Grond, Kevin Kalasz, and Mark Peck for administrative, field, and logistical support; Theunis Piersma, Anne Dekinga, and Anneke Bol for sending samples and extractions; and Alison Cloutier and anonymous reviewers for valuable comments on earlier drafts. This work was supported by funds to DMB from the Natural Science and Engineering Council of Canada (NSERC PDF-373488-2009) and the Netherlands Organisation for Scientific Research (Rubicon 825.09.0190), and to AJB from NSERC (RGPIN 200–07) and the Royal Ontario Museum Life in Crisis: Schad Gallery of Biodiversity Research Fund.

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Authors and Affiliations

  1. Department of Natural History, Royal Ontario Museum, 100 Queen’s Park, Toronto, M5S 2C6, ON, Canada

    Deborah M. Buehler, Yvonne I. Verkuil, Erika S. Tavares & Allan J. Baker

  2. Department of Ecology and Evolutionary Biology, University of Toronto, 25 Willcocks Street, Toronto, M5S 3B2, ON, Canada

    Deborah M. Buehler & Allan J. Baker

  3. Animal Ecology Group, Centre for Ecological and Evolutionary Studies, University of Groningen, Nijenborgh 7, Groningen, 9747, AG, Netherlands

    Yvonne I. Verkuil

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  1. Deborah M. Buehler
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Correspondence to Deborah M. Buehler.

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Fig. S1

Alignment of exon 1 (signal peptide), exon 4 (α3 domain) and exons 5 to 8 (transmembrane and cytoplasmic domains) in Red Knot and Red-billed Gull MHCI amino acid sequences with chicken and goose as outgroups (see Fig. 2 for exons 2 and 3). In exon 4, CD8 binding sites are shown by yellow annotations and intra- and inter-domain contacts by purple triangles. Sequence sources are Gaga (chicken, G. gallus BF2, AL023516), Anan (domestic goose, A. anser, MHC class I antigen gene, AY387655), Lasc (Red-billed Gull, L. scopulinus, UAA, HM008713, UBA, HM008714, UCA, HM008715, UDA, HM008716). Separate alignments for different exons show only alleles with coverage across the exon in question. The first residue of the signal peptide is alignment position 1 (the start codon M) (DOC 535 kb)

Table S1

A complete list of primers used to partially characterize knot MHCI. Melting temperatures (T m ) were calculated using FastPCR v 5.4.54 (DOC 254 kb)

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Buehler, D.M., Verkuil, Y.I., Tavares, E.S. et al. Characterization of MHC class I in a long-distance migrant shorebird suggests multiple transcribed genes and intergenic recombination. Immunogenetics 65, 211–225 (2013). https://doi.org/10.1007/s00251-012-0669-2

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