SpringerLink
Log in

MHC class II DRB1 and DQA2 gene polymorphisms in four indigenous breeds of sheep (Ovis aries)

  • Original investigation
  • Published:
Mammalian Biology Aims and scope Submit manuscript

Abstract

Major histocompatibility complex (MHC) contains highly polymorphic genes, coding receptors that participate in the immune responses. Information of MHC polymorphism from domestic animals could be used in genetic improvement programs and could contribute to the understanding of the impact of domestication or human influence. Here, we studied the highly polymorphic genes DRB1 and DQA2 in four Mediterranean breeds of domestic sheep (Ovis aries), using SSCP method in combination with sequencing. In total 48 Ovar-DRB1 and 46 Ovar-DQA2 alleles were detected. For both genes high levels of polymorphism were recorded; DRB1 had higher functional polymorphism in the peptide binding region (PBR) whereas DQA2 had a remarkable amino acid polymorphism at full-length exon. This polymorphism detected in O. aries is consistent with heterozygote and rare allele advantage, the main mechanisms of balancing selection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Achour, A., 2001. Major Histocompatibility Complex (MHC): Interaction with Peptides. Encyclopedia of Life Sciences, Mc Millan References Ltd, Groveı´s Dictionaries, Nature Publications.

    Google Scholar 

  • Amills, M., Francino, O., Sánchez, A., 1995. Nested PCR allows the characterization of TaqI and PstI RFLPs in the second exon of the caprine MHC Class II DRB gene. Vet. Immunol. Immunopathol. 48, 313–321.

    Article  CAS  PubMed  Google Scholar 

  • Amills, M., Ramiya, V., Norimine, J., Lewin, H.A., 1998. The major histocompatibility complex of ruminants. Rev. Sci. Tech. 17, 108–120.

    Article  CAS  PubMed  Google Scholar 

  • Andersson, L., Rask, L., 1988. Characterization of the MHC class II region in cattle: the number of DQgenes varies between haplotypes. Immunogenetics 27, 110–120.

    Article  CAS  PubMed  Google Scholar 

  • Archie, E.A., Henry, T., Maldonado, J.E., Moss, C.J., Poole, J.H., Pearson, V.R., Murray, S., Alberts, S.C., Fleischer, R.C., 2010. Major histocompatibility complex variation and evolution at a single: expressed DQA locus in two genera of elephants. Immunogenetics 62, 85–100.

    Article  CAS  PubMed  Google Scholar 

  • Ballingall, K.T., Steele, P., Lantier, I., Cotelli, M., Todd, H., Lopez, G., Martin, E., Lantier, F., 2015. An ancient interlocus recombination increases class II MHC DQA diversity in sheep and other Bovidae. Anim. Genet. 46, 333–336.

    Article  CAS  PubMed  Google Scholar 

  • Beck, K., 1984. Coevolution: mathematical analysis of host-parasite interactions. J. Math. Biol. 19, 63–77.

    Article  CAS  PubMed  Google Scholar 

  • Belkhir, K., 1999. GENETIX, Logiciel Sous Windows Pour Lagénétique Des Populations, Laboratoire Génome Et Populations, CNRS UPR 9060. Universiteí de Montpellier II, Montpellier (France).

  • 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  CAS  Google Scholar 

  • Bodmer, W.F., 1972. Evolutionary significance of the HL-A system. Nature 237, 139–145.

    Article  CAS  PubMed  Google Scholar 

  • Deverson, E.V., Wright, H., Watson, S., Ballingall, K., Huskisson, N., Diamond, A.G., Howard, J.C., 1991. Class II major histocompatibility complex genes of the sheep. Anim. Genet. 22, 211–225.

    Article  CAS  PubMed  Google Scholar 

  • Doherty, P.C., Zinkernagel, R.M., 1975. Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex. Nature 256, 50–52.

    Article  CAS  PubMed  Google Scholar 

  • Dukkipati, V.S., Blair, H.T., Garrick, D.J., Murray, A., 2006. ‘Ovar-Mhc’ - ovine major histocompatibility complex: structure and gene polymorphisms. Genet. Mol. Res. 5, 581–608.

    CAS  PubMed  Google Scholar 

  • Ellis, S.A., Bontrop, R.E., Antczak, D.F., Ballingall, K., Davies, C.J., Kaufman, J., Kennedy, L.J., Robinson, J., Smith, D.M., Stear, M.J., Stet, R.J., Waller, M.J., Walter, L., Marsh, S.G., 2006. ISAG/IUIS-VIC comparative MHC nomenclature committee report, 2005: ISAG/IUIS-VIC comparative MHC nomenclature committee. Immunogenetics 12, 953–958.

    Article  Google Scholar 

  • Escayg, A.P., Hickford, J.G., Montgomery, G.W., Dodds, K.G., Bullock, D.W., 1996. Polymorphism at the ovine major histocompatibility complex class II loci. Anim. Genet. 27, 305–312.

    Article  CAS  PubMed  Google Scholar 

  • Excoffier, L., Smouse, P.E., Quattro, J.M., 1992. Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial-DNA restriction data. Genetics 131, 479–491.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fabb, S.A., Maddox, J.F., Gogolin-Ewens, K.J., Baker, L., Wu, M.J., Brandon, M.R., 1993. Isolation, characterization and evolution of ovine major histocompatibility complex class II DRA and DQA genes. Anim. Genet. 24, 249–255.

    Article  CAS  PubMed  Google Scholar 

  • FAO, 2015. The Second Report on The State of the World’s Animal Genetic Resources for Food and Agriculture. Available at: https://doi.org/www.fao.org/publications/sowangr/en//.

  • Goda, N., Mano, T., Masuda, R., 2009. Genetic diversity of the MHC class-II DQA gene in brown bears (Ursus arctos) on Hokkaido, Northern Japan. Zool. Sci. 26, 530–535.

    Article  CAS  Google Scholar 

  • Goudet, J., 2001. FSTAT, a Program to Estimate and Test Gene Diversities and Fixation Indices (version 2.9.3), Available at: https://doi.org/www2.unil.ch/popgen/softwares/fstat.html. Updated from Goudet 1995.

  • Hedrick, P.W., Kim, T.J., 2000. Genetics of complex polymorphisms: parasites and maintenance of the major histocompatibility complex variation. In: Singh, R.S., Krimbas, C.B. (Eds.), Evolutionary Genetics. From Molecules to Morphology. Cambridge University Press, Cambridge, pp. 204–234.

    Google Scholar 

  • Hickford, J.G., Zhou, H., Slow, S., Fang, Q., 2004. Diversity of the ovine DQA2gene. J. Anim. Sci. 82, 1553–1563.

    Article  CAS  PubMed  Google Scholar 

  • Hughes, A.L., Nei, M., 1988. Pattern of nucleotide substitution at major histocompatibility complex class I locus reveals overdominant selection. Nature 335, 167–170.

    Article  CAS  PubMed  Google Scholar 

  • Hughes, A.L., Nei, M., 1990. Evolutionary relationships of class II major-histocompatibility-complex genes in mammals. Mol. Biol. Evol. 7, 491–514.

    CAS  PubMed  Google Scholar 

  • Hughes, A.L., Yeager, M., 1998. Comparative evolutionary rates of introns and exons in murine rodents. J. Mol. Evol. 46, 497.

    Article  CAS  PubMed  Google Scholar 

  • Hughes, A., Yeager, M., Carrington, M., 1996. Peptide binding function and the paradox of HLA disease associations. Immunol. Cell. Biol. 74, 444–448.

    Article  CAS  PubMed  Google Scholar 

  • Jukes, T.H., Cantor, C.R., 1969. Evolution of protein molecules. In: Munro, H.N. (Ed.), Mammalian Protein Metabolism. Academic, New York, pp. 21–123.

    Chapter  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Klein, J., Figueroa, F., 1986. Evolution of the major histocompatibility complex. Crit. Rev. Immunol. 6, 295–386.

    CAS  PubMed  Google Scholar 

  • Klein, J., Sato, A., Nagl, S., O’hUigin, C., 1998. Molecular transspecies polymorphism. Ann. Rev. Ecol. Syst. 29, 1–21.

    Article  Google Scholar 

  • Koutsogiannouli, E.A., Moutou, K.A., Sarafidou, T., Stamatis, C., Spyrou, V., Mamuris, Z., 2009. Major histocompatibility complex variation at class II DQA locus in the brown hare (Lepus europaeus). Mol. Ecol. 18, 4631–4649.

    Article  CAS  PubMed  Google Scholar 

  • Koutsogiannouli, E.A., Moutou, K.A., Stamatis, C., Walter, L., Mamuris, Z., 2014. Genetic variation in the major histocompatibility complex of the European brown hare (Lepus europaeus) across distinct phylogeographic areas. Immunogenetics 66, 379–392.

    Article  CAS  PubMed  Google Scholar 

  • Larkin, M.A., Blackshields, G., Brown, N.P., Chenna, R., McGettigan, P.A., McWilliam, H., Valentin, F., Wallace, I.M., Wilm, A., Lopez, R., Thompson, J.D., Gibson, T.J., Higgins, D.G., 2007. Clustal W and clustal x version 2.0. Bioinformatics 23, 2947–2948.

    Article  CAS  PubMed  Google Scholar 

  • Li, G., Liu, K., Jiao, S., Liu, H., Blair, H.T., Zhang, P., Cui, X., Tan, P., Gao, J., Ma, R.Z., 2012. A physical map of a BAC clone contig covering the entire autosome insertion between ovine MHC Class IIa and IIb. BMC Genomics 16, 398–411.

    Article  CAS  Google Scholar 

  • Luetkemeier, E.S., Malhi, R.S., Beever, J.E., Schook, L.B., 2009. Diversification of porcine MHC class II genes: evidence for selective advantage. Immunogenetics 2, 119–129.

    Article  CAS  Google Scholar 

  • Mahdy, E.A., Mäkinen, A., Chowdhary, B.P., Andersson, L., Gustavsson, I., 1989. Chromosomal localization of the ovine major histocompatibility complex (OLA) by in situ hybridization. Hereditas 111, 87–90.

    CAS  PubMed  Google Scholar 

  • Mikko, S., Spencer, M., Morris, B., Stabile, S., Basu, T., Stormont, C., Andersson, L., 1997. A comparative analysis of Mhc DRB3 polymorphism in the American bison (Bison bison).J. Hered. 88, 499–503.

    Article  CAS  Google Scholar 

  • Moutou, K.A., Koutsogiannouli, E.A., Stamatis, C., Billinis, C., Kalbe, C., Scandura, M., Mamuris, Z., 2013. Domestication does not narrow MHC diversity in Sus scrofa. Immunogenetics 65, 195–209.

    Article  CAS  PubMed  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.

    CAS  PubMed  Google Scholar 

  • Plasil, M., Mohandesan, E., Fitak, R.R., Musilova, P., Kubickova, S., Burger, P.A., Horin, P., 2016. The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes. BMC Genomics 17, 167.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Scott, P.C., Choi, C.L., Brandon, M.R., 1987. Genetic organization of the ovine MHC class II region. Immunogenetics 25, 116–122.

    Article  CAS  PubMed  Google Scholar 

  • Scott, P.C., Gogolin-Ewens, K.J., Adams, T.E., Brandon, M.R., 1991. Nucleotide sequence, polymorphism, and evolution of ovine MHC class II DQA genes. Immunogenetics 34, 69–79.

    CAS  PubMed  Google Scholar 

  • Seddon, J.M., Ellegren, H., 2002. MHC class II genes in European wolves: a comparison with dogs. Immunogenetics 54, 490–500.

    Article  CAS  PubMed  Google Scholar 

  • Seifertová, M., Jarkovsky, J., Simková, A., 2015. Does the parasite-mediated selection drive the MHC class IIB diversity in wild populations of European chub (Squalius cephalus)? Parasitol. Res. (Epub ahead of print).

  • Slade, R.W., McCallum, H.I., 1992. Overdominant vs. frequency-dependent selection at MHC loci. Genetics 132, 861–864.

    CAS  PubMed  Google Scholar 

  • Snell, G.D., 1968. The H-2 locus of the mouse: observations and speculations concerning its comparative genetics and its polymorphism. Folia Biol. 14, 335–358.

    CAS  Google Scholar 

  • Snibson, K.J., Maddox, J.F., Fabb, S.A., Brandon, M.R., 1998. Allelic variation of ovine MHC class II DQA1 and DQA2 genes. Anim. Genet. 29, 356–362.

    Article  CAS  PubMed  Google Scholar 

  • Sommer, S., 2005. The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Front. Zool. 2, 16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stone, R.T., Muggli-Cockett, N.E., 1990. Partial nucleotide sequence of a novel bovine major histocompatibility complex class II betachain gene, BoLA-DIB. Anim. Genet. 21, 353–360.

    Article  CAS  PubMed  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  CAS  PubMed  PubMed Central  Google Scholar 

  • Ujvari, B., Belov, K., 2011. Major histocompatibility complex (MHC) markers in conservation biology. Int. J. Mol. Sci. 12, 5168–5186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wright, H., Ballingall, K.T., 1994. Map** and characterization of the DQ subregion of the ovine MHC. Anim. Genet. 25, 243–249.

    Article  CAS  PubMed  Google Scholar 

  • Wright, H., Ballingall, K.T., Redmond, J., 1994. The DY sub-region of the sheep MHC contains and A/Bgene pair. Immunogenetics 40, 230–234.

    Article  CAS  PubMed  Google Scholar 

  • van der Poel, J.J., Groenen, M.A., Dijkhof, R.J., Ruyter, D., Giphart, M.J., 1990. The nucleotide sequence of the bovine MHC class II alpha genes: DRA, DOA, and DYA. Immunogenetics 31, 29–36.

    Article  PubMed  Google Scholar 

  • Yuhki, N., Beck, T., Stephens, R.M., Nishigaki, Y., Newmann, K., O’Brien, S.J., 2003. Comparative genome organization of human, murine, and feline MHC class II region. Genome Res. 13, 1169–1179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Genetics, Evolutionary and Comparative Biology, Department of Biochemistry and Biotechnology, University of Thessaly, 26 Ploutonos St., 41221, Larissa, Greece

    Evangelia A. Koutsogiannouli, Katerina A. Moutou, Costas Stamatis & Zissis Mamuris

Authors
  1. Evangelia A. Koutsogiannouli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katerina A. Moutou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Costas Stamatis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zissis Mamuris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zissis Mamuris.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koutsogiannouli, E.A., Moutou, K.A., Stamatis, C. et al. MHC class II DRB1 and DQA2 gene polymorphisms in four indigenous breeds of sheep (Ovis aries). Mamm Biol 81, 628–636 (2016). https://doi.org/10.1016/j.mambio.2016.08.002

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.mambio.2016.08.002

Keywords

Search

Navigation