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Isolation and characterization of a MHC class II DRB locus in the European water vole (Arvicola terrestris)

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Abstract

In so-called model species, such as human and mouse, genes of the major histocompatibility complex (MHC) are characterized by extremely high levels of polymorphism, and it is considered that such diversity is maintained by balancing selection. `There is now a recognized need to expand studies into nonmodel species to examine whether high MHC diversity is mirrored in natural populations, and to determine the ecological, ethological, and evolutionary processes that underpin balancing selection. To address such issues, a necessary prerequisite is the ability to characterize diversity at a single, expressed, polymorphic MHC locus on which selection may be acting. Here, we provide the first description of allelic diversity at exon 2 of an MHC class II DRB locus in the European water vole (Arvicola terrestris), characterize variation across four natural populations, and test whether the patterns of variation are consistent with the effects of balancing selection. Using single-strand conformation polymorphism analysis and subsequent DNA sequencing of gel excisions, five DRB alleles were resolved, each with a unique amino acid sequence, among 100 individuals from four geographically distinct populations. Reverse transcription polymerase chain reaction confirmed that the alleles were products from an expressed locus. Intra-allelic amino acid differences were high (10.5–33.3%), and the nonsynonymous substitution rate exceeded the synonymous substitution rate for the functional peptide-binding region (d N:d S=3.91 and P<0.005). Phylogenetic comparison of resolved alleles with closely related homologues indicated that each allele represented a unique lineage preserved across speciation events. These results indicate that balancing selection has maintained diversity of DRB allelic lineages and amino acid function over evolutionary time scales, but may be less effective at preserving alleles in contemporary populations where stochastic microevolutionary processes may dominate.

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References

  • Akaike H (1974) A new look at statistical model identification. IEEE Trans Automat Contr 19:716–723

    Article  Google Scholar 

  • Apanius V, Penn D, Slev PR, Ruff LR, Potts WK (1997) The nature of selection on the major histocompatibility complex. CRC Crit Rev Immunol 17:179–224

    CAS  Google Scholar 

  • Bernatchez L, Landry C (2003) MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years? J Evol Biol 16:363–377

    Article  PubMed  CAS  Google Scholar 

  • Bowen L, Aldridge BM, Gulland F, Van Bonn W, DeLong R, Melin S, Lowenstine LJ, Stott JL, Johnson ML (2004) Class II multiformity generated by variable MHC-DRB region configurations in the California sea lion (Zalophus californianus). Immunogenetics 56:12–27

    Article  PubMed  CAS  Google Scholar 

  • Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC (1993) 3-Dimensional structure of the human class-II histocompatibility antigen Hla-Dr1. Nature 364:33–39

    Article  PubMed  CAS  Google Scholar 

  • Doxiadis GGM, Otting N, de Groot NG, Noort R, Bontrop RE (2000) Unprecedented polymorphism of Mhc-DRB region configurations in rhesus macaques. J Immunol 164:3193–3199

    PubMed  CAS  Google Scholar 

  • Doxiadis GGM, Otting N, de Groot NG, Bontrop RE (2001) Differential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies. Immunol Rev 183:76–85

    Article  PubMed  CAS  Google Scholar 

  • Edwards SV, Hedrick PW (1998) Evolution and ecology of MHC molecules: from genomics to sexual selection. Trends Ecol Evol 13:305–311

    Article  Google Scholar 

  • Egid K, Brown JL (1989) The major histocompatibility complex and female mating preferences in mice. Anim Behav 38:548–550

    Article  Google Scholar 

  • Ekblom R, Grahn M, Hoglund J (2003) Patterns of polymorphism in the MHC class II of a non-passerine bird, the great snipe (Gallinago media). Immunogenetics 54:734–741

    PubMed  CAS  Google Scholar 

  • Ellegren H, Hartman G, Johansson M, Andersson L (1993) Major histocompatibility complex monomorphism and low levels of DNA fingerprinting variability in a reintroduced and rapidly expanding population of beavers. Proc Natl Acad Sci U S A 90:8150–8153

    Article  PubMed  CAS  Google Scholar 

  • Ellegren H, Mikko S, Wallin K, Andersson L (1996) Limited polymorphism at major histocompatibility complex (MHC) loci in the Swedish moose A. alces. Mol Ecol 5:3–9

    Article  PubMed  CAS  Google Scholar 

  • Felsenstein J (1985) Confidence-limits on phylogenies—an approach using the bootstrap. Evolution 39:783–791

    Article  Google Scholar 

  • Figueroa F, Mayer WE, Sultmann H, O’hUigin C, Tichy H, Satta Y, Takezaki N, Takahata N, Klein J (2000) Mhc class IIB gene evolution in East African cichlid fishes. Immunogenetics 51:556–575

    Article  PubMed  CAS  Google Scholar 

  • Froeschke G, Sommer S (2005) MHC Class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. Mol Biol Evol 22:1254–1259

    Article  PubMed  CAS  Google Scholar 

  • Garrigan D, Hedrick PN (2001) Class I MHC polymorphism and evolution in endangered California Chinook and other Pacific salmon. Immunogenetics 53:483–489

    Article  PubMed  CAS  Google Scholar 

  • Garrigan D, Hedrick PW (2003) Perspective: detecting adaptive molecular polymorphism: lessons from the MHC. Evolution 57:1707–1722

    PubMed  CAS  Google Scholar 

  • Gaudieri S, Dawkins RL, Habara K, Kulski JK, Gojobori T (2000) SNP profile within the human major histocompatibility complex reveals an extreme and interrupted level of nucleotide diversity. Genome Res 10:1579–1586

    Article  PubMed  CAS  Google Scholar 

  • Go Y, Satta Y, Kawamoto Y, Rakotoarisoa G, Randrianjafy A, Koyama N, Hirai H (2002) Mhc-DRB genes evolution in lemurs. Immunogenetics 54:403–417

    Article  PubMed  CAS  Google Scholar 

  • Harf R, Sommer S (2005) Association between major histocompatibility complex class II DRB alleles and parasite load in the hairy-footed gerbil, Gerbillurus paeba, in the southern Kalahari. Mol Ecol 14:85–91

    Article  PubMed  CAS  Google Scholar 

  • Klein J (1980) Generation of diversity at MHC loci: implications for T-cell receptor repertoires. In: Fougereau M, Dausset J (eds) Immunology 80. Academic, London, pp 239–253

    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 

  • Kriener K, O’hUigin C, Klein J (2000a) Alu elements support independent origin of prosimian, platyrrhine, and catarrhine Mhc-DRB genes. Genome Res 10:634–643

    Article  PubMed  CAS  Google Scholar 

  • Kriener K, O’hUigin C, Tichy H, Klein J (2000b) Convergent evolution of major histocompatibility complex molecules in humans and New World monkeys. Immunogenetics 51:169–178

    Article  PubMed  CAS  Google Scholar 

  • Kumar S, Tamura K, Nei M (2004) MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163

    Article  PubMed  CAS  Google Scholar 

  • Lambin X, Aars J, Piertney SB, Telfer S (2004) Inferring pattern and process in small mammal metapopulations: insights from ecological and genetic data. In: Hanski I, Gaggiotti OE (eds) Ecology, genetics, and evolution of metapopulations. Elsevier Academic, Burlington, pp 515–540

    Chapter  Google Scholar 

  • Meyer-Lucht Y, Sommer S (2005) MHC diversity and the association to nematode parasitism in the yellow-necked mouse (Apodemus flavicollis). Mol Ecol 14:2233–2243

    Article  PubMed  CAS  Google Scholar 

  • Muirhead CA (2001) Consequences of population structure on genes under balancing selection. Evolution 55:1532–1541

    PubMed  CAS  Google Scholar 

  • Mullenbach R, Lagoda PJL, Welter C (1989) An efficient salt–chloroform extraction of DNA from blood and tissues. Trends Genet 5:391

    PubMed  CAS  Google Scholar 

  • Musolf K, Meyer-Lucht Y, Sommer S (2004) Evolution of MHC-DRB class II polymorphism in the genus Apodemus and a comparison of DRB sequences within the family Muridae (Mammalia: Rodentia). Immunogenetics 56:420–426

    Article  PubMed  CAS  Google Scholar 

  • Nei M, Gojobori T (1986) Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426

    PubMed  CAS  Google Scholar 

  • Nei M, Kumar S (2000) Molecular evolution and phylogenetics. Oxford University Press, New York

    Google Scholar 

  • Nizetic D, Figueroa F, Dembic Z, Nevo E, Klein J (1987) Major Histocompatibility complex gene organization in the mole rat Spalax ehrenbergi: evidence for transfer of function between class II genes. Proc Natl Acad Sci U S A 84:5828–5832

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Posada D, Crandall KA (1998) MODELTEST: testing the model of DNA substitution. Bioinformatics 14:817–818

    Article  PubMed  CAS  Google Scholar 

  • Schad J, Sommer S, Ganzhorn JU (2004) MHC variability of a small lemur in the littoral forest fragments of southeastern Madagascar. Conservation Genetics 5:299–309

    Article  CAS  Google Scholar 

  • Smulders MJM, Snoek LB, Booy G, Vosman B (2003) Complete loss of MHC genetic diversity in the common hamster (Cricetus cricetus) population in The Netherlands. Consequences for conservation strategies. Conservation Genetics 4:441–451

    Article  CAS  Google Scholar 

  • Sommer S, Schwab D, Ganzhorn JU (2002) MHC diversity of endemic Malagasy rodents in relation to geographic range and social system. Behav Ecol Sociobiol 51:214–221

    Article  Google Scholar 

  • Strachan C, Strachan R, Jeffries D (2000) Preliminary report on the changes of the water vole population of Britain as shown by the national survey of 1989–1990 and 1996–1998. The Vincent Wildlife Trust, London

    Google Scholar 

  • Swofford DL (1998) PAUP* Phylogenetic analysis using parsimony (and other methods). Sinauer Associates, Sunderland, MA

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki K, Boyse EA, Mike V, Thaler HT, Mathieson BJ, Abbott J, Boyse J, Zayas ZA (1976) Control of mating preferences in mice by genes in the major histocompatibility complex. J Exp Med 144:1324–1335

    Article  PubMed  CAS  Google Scholar 

  • Yuhki N, Beck T, Stephens RM, Nishigaki Y, Newmann K, O’Brien SJ (2003) Comparative genome organization of human, murine, and feline MHC class II region. Genome Res 13:1169–1179

    Article  PubMed  CAS  Google Scholar 

  • Zylstra P, Rothenfluh H, Weiller GF, Blanden RV, Steele EJ (1998) PCR amplification of murine immunoglobulin germline V genes: strategies for minimization of recombination artefacts. Immunol Cell Biol 76:395–405

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Xavier Lambin, Sandra Telfer, Jon Aars, Edoardo Tedesco, Vicki Saint, Jamie Urquhart, Suzanne Hogg, Elaine Fraser, and Laura Taylor for assistance with sample collection. This work was carried out under the tenure of a Natural Environment Research Council (NERC) postgraduate studentship to MKO.

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  1. School of Biological Sciences, University of Aberdeen, Zoology Building, Tillydrone Avenue, Aberdeen, Scotland, AB24 2TZ, UK

    Matthew K. Oliver & Stuart B. Piertney

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  1. Matthew K. Oliver
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  2. Stuart B. Piertney
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Correspondence to Matthew K. Oliver.

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Oliver, M.K., Piertney, S.B. Isolation and characterization of a MHC class II DRB locus in the European water vole (Arvicola terrestris). Immunogenetics 58, 390–395 (2006). https://doi.org/10.1007/s00251-006-0121-6

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  • DOI: https://doi.org/10.1007/s00251-006-0121-6

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