Acta Theriologica

, Volume 52, Issue 3, pp 227–235 | Cite as

Sequence diversity of MHC class II DRB genes in the bank voleMyodes glareolus



In recent years, the bank voleMyodes glareolus (Schreber, 1780) has emerged as a model system for parasitological, behavioural and ecological studies and seems ideally suited to address questions concerning the importance of MHC variation at individual and population levels. Here, we provide the first extensive survey of sequence variation in the MHC class II DRB genes in this species. Among 34 analysed voles we found 15 unique sequences, representing most likely two loci, at least one of them expressed. Despite very high overall sequence divergence, particularly in the Antigen Binding Sites (ABS), we detected signatures of positive selection that has been acting on DRB in the bank vole. Phylogenetic analysis demonstrated that the bank vole DRB alleles do not form a monophyletic group but are intermingled with other rodent alleles that is consistent with long-term persistence of ancient allelic lineages maintained through balancing selection. Our sequence data will forward the design of efficient genotyping methods, which will permit testing hypotheses pertaining to the ecological causes and consequences of MHC variation in the bank vole.

Key words

Major Histocompatibility Complex polymorphism rodents selection recombination 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bajer A., Pawełczyk A., Behnke J. M., Gilbert F. S. and Siński E. 2001. Factors affecting the component community structure of haemoparasites in bank voles (Clethrionomys glareolus) from the Mazury Lake District region of Poland. Parasitology 122: 43–54.CrossRefPubMedGoogle Scholar
  2. Behnke J. M., Bajer A., Siński E. and Wakelin D. 2001. Interactions involving intestinal nematodes of rodents in experimental and field studies. Parasitology 122: S39-S49.CrossRefPubMedGoogle Scholar
  3. Bernatchez L. and Landry C. 2003. MHC studies in non-model vertebrates: what have we learned about natural selection in 15 years? Journal of Evolutionary Biology 16: 363–377.CrossRefPubMedGoogle Scholar
  4. Borghans J. A. M., Beltman J. B. and De Boer R. J. 2004. MHC polymorphism under host-pathogen coevolution. Immunogenetics 55: 732–739.CrossRefPubMedGoogle Scholar
  5. Brown J. H., Jardetzky T. S., Gorga J. C., Stern L. J., Urban R. G., Strominger J. L. and Wiley D. C. 1993. 3-Dimensional structure of the human class-II histocompatibility antigen HLA-DR1. Nature 364:33–399.CrossRefPubMedGoogle Scholar
  6. Bryja J., Galan M., Charbonnel N. and Cosson J. F. 2006. Duplication, balancing selection and trans-species evolution explain the high levels of polymorphism of the DQA MHC class II gene in voles (Arvicolinae). Immunogenetics 58: 191–202.CrossRefPubMedGoogle Scholar
  7. Deffontaine V., Libois R., Kotlik P., Sommer R., Nieberding C., Paradis E., Searle J. B. and Michaux J. 2005. Beyond the Mediterranean peninsulas: evidence of central European glacial refugia for a temperate forest mammal species, the bank vole (Clethrionomys glareolus). Molecular Ecology 14: 1727–1739.CrossRefPubMedGoogle Scholar
  8. Doherty P. C. and Zinkernagel R. M. 1975. Enhanced immunological surveillance in mice heterozygous at H-2 gene complex. Nature 256: 50–52.CrossRefPubMedGoogle Scholar
  9. Edwards S. V., Chesnut K., Satta Y. and Wakeland E. K. 1997. Ancestral polymorphism of MHC class II genes in mice: Implications for balancing selection and the mammalian molecular clock. Genetics 146: 655–668.PubMedGoogle Scholar
  10. Fraser D. G. and Bailey E. 1996. Demonstration of three DRB loci in a domestic horse family. Immunogenetics 44: 441.CrossRefPubMedGoogle Scholar
  11. Garrigan D. and Hedrick P. W. 2003. Perspective: Detecting adaptive molecular polymorphism: Lessons from the MHC. Evolution 57: 1707–1722.PubMedGoogle Scholar
  12. Harf R. and 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. Molecular Ecology 14: 85–91.CrossRefPubMedGoogle Scholar
  13. Janeway C. A., Travers P., Walport D. and Capra J. D. 1999. Immunobiology: The Immune System in Health and Disease. Current Biology Publications, London: 1–635.Google Scholar
  14. Jarvi S. I., Tarr C. L., McIntosh C. E., Atkinson C. T. and Fleischer R. C. 2004. Natural selection of the major histocompatibility complex (MHC) in Hawaiian honeycreepers (Drepanidinae). Molecular Ecology 13: 2157–2168.CrossRefPubMedGoogle Scholar
  15. Karbowiak G., Rychlik L., Nowakowski W. and Wita I. 2005. Natural infections with blood parasites on the borderland of boreal and temperate forest zones. Acta Theriologica 50: 31–42.CrossRefGoogle Scholar
  16. Kennedy L. J., Ryvar R., Gaskell R. M., Addie D. D., Willoughby K., Carter S. D., Thomson W., Ollier W. E. R. and Radford A. D. 2002. Sequence analysis of MHC DRB alleles in domestic cats from the United Kingdom. Immunogenetics 54: 348–352.CrossRefPubMedGoogle Scholar
  17. Khazand M., Peiberg C., Nagy M. and Sauermann U. 1999. MHC-DQ-DRB haplotype analysis in the rhesus macaque: evidence for a number of different haplotypes displaying a low allelic polymorphism. Tissue Antigens 54: 615–624.CrossRefPubMedGoogle Scholar
  18. Klein J. 1987. Origin of Major Histocompatibility Complex polymorphism — the transspecies hypothesis. Human Immunology 19: 155–162.CrossRefPubMedGoogle Scholar
  19. Klein J., Bontrop R. E., Dawkins R. L., Erlich H. A., Gyllensten U. B., Heise E. R., Jones P. P., Parham P., Wakeland E. K. and Watkins D. I. 1990. Nomenclature for the Major Histocompatibility Complexes of different species — a proposal. Immunogenetics 31: 217–219.PubMedGoogle Scholar
  20. Koskela E., Huitu O., Koivula M., Korpimaki E. and Mappes T. 2004. Sex-biased maternal investment in voles: importance of environmental conditions. Proceedings of the Royal Society of London Series B-Biological Sciences 271: 1385–1391.CrossRefGoogle Scholar
  21. Kotlik P., Deffontaine V., Mascheretti S., Zima J., Michaux J. R. and Searle J. B. 2006. A northern glacial refugium for bank voles (Clethrionomys glareolus). Proceedings of the National Academy of Sciences of the United States of America 103: 14860–14864.CrossRefPubMedGoogle Scholar
  22. Kumar S., Tamura K. and Nei M. 2004. MEGA3: Integrated software for molecular evolutionary genetics analysis and sequence alignment. Briefings in Bioinformatics 5: 150–163.CrossRefPubMedGoogle Scholar
  23. Labocha M. K., Sadowska E. T., Baliga K., Semer A. K. and Koteja P. 2004. Individual variation and repeatability of basal metabolism in the bank vole,Clethrionomys glareolus. Proceedings of the Royal Society of London Series B-Biological Sciences 271: 367–372.CrossRefGoogle Scholar
  24. Martin D. and Rybicki E. 2000. RDP: detection of recombination amongst aligned sequences. Bioinformatics 16: 562–563.CrossRefPubMedGoogle Scholar
  25. Maynard Smith J. 1992. Analyzing the Mosaic Structure of Genes. Journal of Molecular Evolution 34: 126–129.Google Scholar
  26. Milinski M. 2006. The major histocompatibility complex, sexual selection, and mate choice. Annual Review of Ecology Evolution and Systematics 37: 159–186.CrossRefGoogle Scholar
  27. Musolf K., Meyer-Lucht Y. and Sommer S. 2004. Evolution of MHC-DRB class II polymorphism in the genusApodemus and a comparison of DRB sequences within the family Muridae (Mammalia: Rodentia). Immunogenetics 56: 420–426.CrossRefPubMedGoogle Scholar
  28. Oliver M. K. and Piertney S. B. 2006. Isolation and characterization of a MHC class II DRB locus in the European water vole (Arvicola terrestris). Immunogenetics 58: 390–395.CrossRefPubMedGoogle Scholar
  29. Padidam M., Sawyer S. and Fauquet C. M. 1999. Possible emergence of new geminiviruses by frequent recombination. Virology 265: 218–225.CrossRefPubMedGoogle Scholar
  30. Paterson S., Wilson K. and Pemberton J. M. 1998. Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.). Proceedings of the National Academy of Sciences of the United States of America 95: 3714–3719.CrossRefPubMedGoogle Scholar
  31. Penn D. J., Damjanovich K. and Potts W. K. 2002. MHC heterozygosity confers a selective advantage against multiple-strain infections. Proceedings of the National Academy of Sciences of the United States of America 99: 11260–11264.CrossRefPubMedGoogle Scholar
  32. Piertney S. B. and Oliver M. K. 2006. The evolutionary ecology of the major histocompatibility complex. Heredity 96: 7–21.PubMedGoogle Scholar
  33. Pond S. L. K., Posada D., Gravenor M. B., Woelk C. H. and Frost S. D. W. 2006. Automated phylogenetic detection of recombination using a genetic algorithm. Molecular Biology and Evolution 23: 1891–1901.CrossRefGoogle Scholar
  34. Posada D. 2002. Evaluation of methods for detecting recombination from DNA sequences: Empirical data. Molecular Biology and Evolution 19: 708–717.PubMedGoogle Scholar
  35. Posada D. and Buckley T. R. 2004. Model selection and model averaging in phylogenetics: Advantages of Akaike Information Criterion and Bayesian approaches over likelihood ratio tests. Systematic Biology 53: 793–808.CrossRefPubMedGoogle Scholar
  36. Posada D. and Crandall K. A. 1998. MODELTEST: testing the model of DNA substitution. Bioinformatics 14: 817–818.CrossRefPubMedGoogle Scholar
  37. Radwan J., Kruczek M., Labocha M. K., Grabiec K. and Koteja P. 2004. Contest winning and metabolic competence in male bank volesClethrionomys glareolus. Behaviour 141: 343–354.CrossRefGoogle Scholar
  38. Richman A. D., Herrera L. G. and Nash D. 2001. MHC class II beta sequence diversity in the deer mouse (Peromyscus maniculatus): implications for models of balancing selection. Molecular Ecology 10: 2765–2773.PubMedGoogle Scholar
  39. Ronquist F. and Huelsenbeck J. P. 2003. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19: 1572–1574.CrossRefPubMedGoogle Scholar
  40. Smulders M. J. M., Snoek L. B., Booy G. and 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.CrossRefGoogle Scholar
  41. Snell G. D. 1968. The H-2 locus of the mouse: observations and speculations concerning its comparative genetics and its polymorphism. Folia Biologica (Prague) 14: 335–358.Google Scholar
  42. Sommer S. 2005. The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Frontiers in Zoology 2: 16.CrossRefPubMedGoogle Scholar
  43. Tavaré S. 1986. Some probabilistic and statistical problems in the analysis of DNA sequences. [In: Some mathematical questions in biology — DNA sequence analysis. R. M. Miura, ed]. American Mathematical Society., Providence: 57–86.Google Scholar
  44. Thursz M. R., Thomas H. C., Greenwood B. M. and Hill A. V. S. 1997. Heterozygote advantage for HLA class-II type in hepatitis B virus infection. Nature Genetics 17: 11–12.CrossRefPubMedGoogle Scholar
  45. Trachtenberg E., Korber B., Sollars C., Kepler T. B., Hraber P. T., Hayes E., Funkhouser R., Fugate M., Theiler J., Hsu Y. S., Kunstman K., Wu S., Phair J., Erlich H. and Wolinsky S. 2003. Advantage of rare HLA supertype in HIV disease progression. Nature Medicine 9: 928–935.CrossRefPubMedGoogle Scholar
  46. Yang Z. H. 1997. PAML: a program package for phylogenetic analysis by maximum likelihood. Computer Applications in the Biosciences 13: 555–556.PubMedGoogle Scholar
  47. Zhang J. Z., Nielsen R. and Yang Z. H. 2005. Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Molecular Biology and Evolution 22: 2472–2479.CrossRefPubMedGoogle Scholar

Copyright information

© Mammal Research Institute, Bialowieza, Poland 2007

Authors and Affiliations

  1. 1.Department of Community EcologyHelmholtz Centre for Environmental Research — UFZHalle/SaaleGermany
  2. 2.Institute of Environmental SciencesJagiellonian UniversityKrakówPoland

Personalised recommendations