Skip to main content
Log in

Estimation of the role of single nucleotide polymorphism in lymphotoxin beta gene during pig domestication based on the bioinformatic and experimental approaches

  • Published:
Russian Journal of Genetics: Applied Research

Abstract

The existence of a tradeoff between the reproductive success and immunity was demonstrated in the works conducted on wild and laboratory animals. Therefore, individuals with an increased reproductive capacity but with decreased immunity could be selected in the process of domestication. A decreased reactivity of the immune system could subsequently become inheritable by fixation of the genes with unfavorable mutations in the population. The aim of the investigation was to study (1) the genotype and allele frequencies of the rs340283541 single nucleotide polymorphism (SNP) in the lymphotoxin beta (LTB) cytokine gene in domestic pigs and wild boars; (2) the mRNA expression for this gene in mini pigs with different genotypes; and (3) to perform the bioinformatic analysis of a potential functional role of this SNP. The GG genotype frequency in the boar sample was significantly lower than this genotype frequency in the combined sample from different domestic pig breeds and populations. The level of the LTB gene mRNA expression in a lymph node in mini pigs with GG genotype had a trend towards an increase (p < 0.06) as compared with the A allele carriers. The rs340283541 SNP is located within the conservative sequence motif revealed in 12 mammalian species (that indirectly indicates important functional role of SNP). By means of the context analysis, it was detected that the A allele contains potential binding sites for the BRN-2 and AP-1 transcription factors, while the G allele contains those for the RFX1, ISGF3 (ISRE site), and USF (that are expressed in the immune system cells). Thus, an increase in the frequency of the rs340283541 SNP (located in the LTB gene 3'-region) GG genotype occurred in the process of pig domestication. The GG genotype is probably associated with an increased level of the LTB gene mRNA expression in the lymph node tissue. An increase in the expression level in pigs with the GG genotype can be associated with generation of the RFX1, ISRE, and USF binding sites and/or damage of the BRN-2 and AP-1 binding sites. It is also possible that the rs340283541 polymorphism is in linkage disequilibrium with another functionally significant mutation.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aitnazarov, R.B., Yudin, N.S., Nikitin, S.V., Yermolaev, V.I., and Voevoda, M.I., Identification of whole genomes of endogenous retroviruses in Siberian miniature pigs, Russ. J. Genet., Appl. Res., 2014, vol. 4, no. 6, pp. 523–525.

    Article  Google Scholar 

  • Ananko, E.A., Kondrakhin, Y.V., Merkulova, T.I., and Kolchanov, N.A., Recognition of interferon-inducible sites, promoters, and enhancers, BMC Bioinf., 2007, vol. 8, p. 56.

    Article  Google Scholar 

  • Ardia, D.R., Parmentier, H.K., and Vogel, L.A., The role of constraints and limitation in driving individual variation in immune response, Functional Ecology, 2011, vol. 25, no. 1, pp. 61–73. doi 10.1111/j.1365-2435.2010.01759.x

    Article  Google Scholar 

  • Balenger, S.L. and Zuk, M., Testing the Hamilton-Zuk hypothesis: Past, present, and future, Integr. Comp. Biol., 2014, vol. 54, no. 4, pp. 601–613. doi 10.1093/icb/icu059

    Article  PubMed  Google Scholar 

  • Belyaev, D.K., Destabilizing selection as a factor of variability in domestication, Priroda (Moscow, Russ. Fed.), 1979, vol. 2, pp. 36–45.

    Google Scholar 

  • Belyaev, D.K., Destabiliziruyushchii otbor kak faktor domestikatsii. Genetika i blagosostoyanie chelovechestva (Destabilizing Selection as a Factor of Domestication. Genetics and Human Well-Being), Moscow, 1981.

    Google Scholar 

  • Corre, S. and Galibert, M.D., USF as a key regulatory element of gene expression, Med. Sci. (Paris), 2006, vol. 22, no. 1, pp. 62–67.

    Article  Google Scholar 

  • Crooks, G.E., Hon, G., Chandonia, J.M., and Brenner, S.E., Weblogo: A sequence logo generator, Genome Res., 2004, vol. 14, no. 6, pp. 1188–1190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crowe, P.D., VanArsdale, T.L., Walter, B.N., Ware, C.F., Hession, C., Ehrenfels, B., Browning, J.L., Din, W.S., Goodwin, R.G., and Smith, C.A., A lymphotoxin-beta-specific receptor, Science, 1994, vol. 264, no. 5159, pp. 707–710.

    Article  CAS  PubMed  Google Scholar 

  • Cui, C.Y., Hashimoto, T., Grivennikov, S.I., Piao, Y., Nedospasov, S.A., and Schlessinger, D., Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation, Proc. Natl. Acad. Sci. U.S.A., 2006, vol. 103, no. 24, pp. 9142–9147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Djebali, S., Davis, C.A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., Xue, C., Marinov, G.K., Khatun, J., Williams, B.A., et al., Landscape of transcription in human cells, Nature, 2012, vol. 489, no. 7414, pp. 101–108. doi 10.1038/nature11233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellmann, L., Joshi, M.B., Resink, T.J., Bosserhoff, A.K., and Kuphal, S., BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells, Lab Invest., 2012, vol. 92, no. 12, pp. 1788–1800. doi 10.1038/labinvest.2012.140

    Article  CAS  PubMed  Google Scholar 

  • Fontes, J.D., Jabrane-Ferrat, N., and Peterlin, B.M., Assembly of functional regulatory complexes on MHC class II promoters in vivo, J. Mol. Biol., 1997, vol. 270, no. 3, pp. 336–345.

    Article  CAS  PubMed  Google Scholar 

  • Goodall, J., Martinozzi, S., Dexter, T.J., Champeval, D., Carreira, S., Larue, L., and Goding, C.R., Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin, Mol. Cell Biol., 2004, vol. 24, no. 7, pp. 2915–2922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heringstad, B., Chang, Y.M., Gianola, D., and Klemetsdal, G., Genetic association between susceptibility to clinical mastitis and protein yield in Norwegian dairy cattle, J. Dairy Sci., 2005, vol. 88, no. 4, pp. 1509–1514.

    Article  CAS  PubMed  Google Scholar 

  • Heringstad, B., Klemetsdal, G., and Steine, T., Selection responses for disease resistance in two selection experiments with Norwegian red cows, J. Dairy Sci., 2007, vol. 90, no. 5, pp. 2419–2426.

    Article  CAS  PubMed  Google Scholar 

  • Hess, J., Angel, P., and Schorpp-Kistner, M., AP-1 subunits: Quarrel and harmony among siblings, J. Cell Sci., 2004, vol. 117, no. 25, pp. 5965–5973.

    Article  CAS  PubMed  Google Scholar 

  • Ignatieva, E.V., Podkolodnaya, O.A., Orlov, Yu.L., Vasiliev, G.V., and Kolchanov, N.A., Regulatory genomics: Combined experimental and computational approaches, Russ. J. Genet., 2015, vol. 51, no. 4, pp. 334–352.

    Article  CAS  Google Scholar 

  • Kel-Margoulis, O.V., Romashchenko, A.G., Kolchanov, N.A., Wingender, E., and Kel, A.E., COMPEL: A database on composite regulatory elements providing combinatorial transcriptional regulation, Nucleic Acids Res., 2000, vol. 28, no. 1, pp. 311–315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kessler, D.S., Veals, S.A., Fu, X.Y., and Levy, D.E., Interferon-alpha regulates nuclear translocation and DNAbinding affinity of ISGF3, a multimeric transcriptional activator, Genes Dev., 1990, vol. 4, no. 10, pp. 1753–1765.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J.Y., Moon, S.M., Ryu, H.J., Kim, J.J., Kim, H.T., Park, C., Kim, K., Oh, B., and Lee, J.K., Identification of regulatory polymorphisms in the TNF-TNF receptor superfamily, Immunogenetics, 2005, vol. 57, no. 5, pp. 297–303.

    Article  CAS  PubMed  Google Scholar 

  • Kolchanov, N.A., Ignatieva, E.V., Ananko, E.A., Podkolodnaya, O.A., Stepanenko, I.L., Merkulova, T.I., Pozdnyakov, M.A., Podkolodny, N.L., Naumochkin, A.N., and Romashchenko, A.G., Transcription regulatory regions database (TRRD): Its status in 2002, Nucleic Acids Res., 2002, vol. 30, no. 1, pp. 312–317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levitsky, V.G., Ignatieva, E.V., Ananko, E.A., Turnaev, I.I., Merkulova, T.I., Kolchanov, N.A., and Hodgman, T.C., Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions, BMC Bioinf., 2007, vol. 8, p. 481.

    Google Scholar 

  • Loos, R.J. and Yeo, G.S., The bigger picture of FTO: The first GWAS-identified obesity gene, Nat. Rev. Endocrinol., 2014, vol. 10, no. 1, pp. 51–61. doi 10.1038/nrendo.2013.227

    Article  CAS  PubMed  Google Scholar 

  • Merkulova, T.I., Ananko, E.A., Ignatieva, E.V., and Kolchanov, N.A., Transcription regulatory codes of eukaryotic genomes, Russ. J. Genet., 2013, vol. 49, no. 1, pp. 29–45.

    Article  CAS  Google Scholar 

  • Mittelstadt, M.L. and Patel, R.C., AP-1 mediated transcriptional repreßsion of matrix metalloproteinase-9 by recruitment of histone deacetylase 1 in response to interferon ß, PLoS One, 2012, vol. 7, no. 8. doi 10.1371/journal. pone.0042152

  • van der Most, P.J., de Jong, B., Parmentier, H.K., and Verhulst, S., Trade-off between growth and immune function: A meta-analysis of selection experiments, Funct. Ecol., 2011, vol. 25, no. 1, pp. 74–80. doi 10.1111/j.1365-2435.2010.01800.x

    Article  Google Scholar 

  • Nakamura, T., Tashiro, K., Nazarea, M., Nakano, T., Sasayama, S., and Honjo, T., The murine lymphotoxin-beta receptor cDNA: Isolation by the signal sequence trap and chromosomal mapping, Genomics, 1995, vol. 30, no. 2, pp. 312–319.

    Article  CAS  PubMed  Google Scholar 

  • Nedospasov, S.A. and Kuprash, D.V., Tumor necrosis factor and lymphotoxin: Physiological functions and importance for cytokine and anti-cytokine therapy, Russ. Mul’tidistsip. Zh., 2008, vol. 12, no. 1, pp. 69–76.

    Google Scholar 

  • Onder, L., Danuser, R., Scandella, E., Firner, S., Chai, Q., Hehlgans, T., Stein, J.V., and Ludewig, B., Endothelial cell-specific lymphotoxin-ß receptor signaling is critical for lymph node and high endothelial venule formation, J. Exp. Med., 2013, vol. 210, no. 3, pp. 465–473. doi 10.1084/jem.20121462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seddon, J.M., Berggren, K.T., and Fleeman, L.M., Evolutionary history of DLA class II haplotypes in canine diabetes mellitus through single nucleotide polymorphism genotyping, Tissue Antigens, 2010, vol. 75, no. 3, pp. 218–226. doi 10.1111/j.1399-0039.2009.01426.x

    Article  CAS  PubMed  Google Scholar 

  • Sheldon, B.C. and Verhulst, S., Ecological immunology: Costly parasite defences and trade-offs in evolutionary ecology, Trends Ecol. Evol., 1996, vol. 11, no. 8, pp. 317–321.

    Article  CAS  PubMed  Google Scholar 

  • Tierney, R., Kirby, H., Nagra, J., Rickinson, A., and Bell, A., The Epstein-Barr virus promoter initiating B-cell transformation is activated by RFX proteins and the B-cell-specific activator protein BSAP/Pax5, J. Virol., 2000, vol. 74, no. 22, pp. 10458–10467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trapezov, O.V., Darwinism and the lessons of practical breeding in Russia, Vavilovskii Zh. Genet. Sel., 2009, vol. 13, no. 2, pp. 249–297.

    Google Scholar 

  • Zhang, G., Li, C., Li, Q., Li, B., Larkin, D.M., Lee, C., Storz, J.F., Antunes, A., Greenwold, M.J., Meredith, R.W., Odeen, A., Cui, J., Zhou, Q., Xu, L., Pan, et al., Comparative genomics reveals insights into avian genome evolution and adaptation, Science, 2014, vol. 346, no. 6215, pp. 1311–1320. doi 10.1126/science.1251385

    CAS  PubMed  Google Scholar 

  • Zhao, F.Q., Octamer-binding transcription factors: Genomics and functions, Front Biosci., 2013, vol. 18, pp. 1051–1071.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. S. Yudin.

Additional information

Original Russian Text © R.B. Aitnazarov, E.V. Ignatieva, N.E. Bazarova, V.G. Levitsky, S.P. Knyazev, Y. Gon, N.S. Yudin, 2015, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2015, Vol. 19, No. 6, pp. 699–706.

Electronic supplementary material

13328_2016_204_MOESM1_ESM.pdf

The allele and genotype frequencies for SNP rs340283541 located in the 3’-flanking region of the LTB gene in pigs of domestic breeds and wild boars

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aitnazarov, R.B., Ignatieva, E.V., Bazarova, N.E. et al. Estimation of the role of single nucleotide polymorphism in lymphotoxin beta gene during pig domestication based on the bioinformatic and experimental approaches. Russ J Genet Appl Res 6, 816–824 (2016). https://doi.org/10.1134/S2079059716070017

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079059716070017

Keywords

Navigation