Skip to main content
Log in

European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes

  • Brief Communication
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

During the last decade, the Toll-like receptors (TLRs) have been extensively studied, and their immense importance in innate immunity is now being unveiled. Here, we report pronounced differences—probably reflecting the domestication process and differences in selective pressure—between wild boars and domestic pigs regarding single nucleotide polymorphisms (SNPs) in TLR genes. The open reading frames of TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace, and Large White origin. In total, 20, 27, and 26 SNPs were detected in TLR1, TLR2, and TLR6, respectively. In TLR1 and TLR2, the numbers of SNPs detected were significantly lower (P ≤ 0.05, P ≤ 0.01) in the wild boars than in the domestic pigs. In the wild boars, one major high frequency haplotype was found in all three genes, while the same pattern was exhibited only by TLR2 in the domestic pigs. The relative frequency of non-synonymous (dN) and synonymous (dS) SNPs was lower for the wild boars than for the domestic pigs in all three genes. In addition, differences in diversity between the genes were revealed: the mean heterozygosity at the polymorphic positions was markedly lower in TLR2 than in TLR1 and TLR6. Because of its localization—in proximity of the bound ligand—one of the non-synonymous SNPs detected in TLR6 may represent species-specific function on the protein level. Furthermore, the codon usage pattern in the genes studied deviated from the general codon usage pattern in Sus scrofa.

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.

Fig. 1
Fig. 2

References

  • Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511. doi:10.1038/nri1391

    Article  CAS  PubMed  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801. doi:10.1016/j.cell.2006.02.015

    Article  CAS  PubMed  Google Scholar 

  • Alvarez B, Revilla C, Doménech N, Pérez C, Martínez P, Alonso F, Ezquerra A, Domíguez J (2008) Expression of toll-like receptor 2 (TLR2) in porcine leukocyte subsets and tissues. Vet Res 39:13. doi:10.1051/vetres:2007051

    Article  PubMed  Google Scholar 

  • Bergman IM, Johansson A, Fossum C, Andersson L, Edfors-Lilja I (2009) Genetic analysis of porcine TLR genes. Vet Immunol Immunopathol 128:218–219. doi:10.1016/j.vetimm.2008.10.022

    Article  Google Scholar 

  • Burkey TE, Skjolaas KA, Dritz SS, Minton JE (2009) Expression of porcine Toll-like receptor 2, 4 and 9 gene transcripts in the presence of lipopolysaccharide and Salmonella enterica serovars typhimurium and choleraesuis. Vet Immunol Immunopathol 130:96–101. doi:10.1016/j.vetimm.2008.12.027

    Article  CAS  PubMed  Google Scholar 

  • Carver TJ, Mullan LJ (2002) Website update: a new graphical interface to EMBOSS. Comp Funct Genomics 3:75–78. doi:10.1002/cfg.136

    Article  CAS  PubMed  Google Scholar 

  • Edfors-Lilja I, Wattrang E, Andersson L, Fossum C (2000) Mapping quantitative trait loci for stress induced alterations in porcine leukocyte numbers and functions. Anim Genet 31:186–193

    Article  CAS  PubMed  Google Scholar 

  • Fang M, Larson G, Ribeiro HS, Li N, Andersson L (2009) Contrasting mode of evolution at a coat color locus in wild and domestic pigs. PLoS Genetics 5:1–6. doi:10.1371/journal.pgen.1000341

    Article  Google Scholar 

  • Gay NJ, Gangloff M (2007) Structure and function of Toll receptors and their ligands. Annu Rev Biochem 76:141–165. doi:10.1146/annurev.biochem.76.060305.151318

    Article  CAS  PubMed  Google Scholar 

  • Giuffra E, Kijas JM, Amarger V, Carlborg Ö, Jeon JT, Andersson L (2000) The origin of the domestic pig: independent domestication and subsequent introgression. Genetics 154:1785–1791

    CAS  PubMed  Google Scholar 

  • Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, Guiet C, Brière F, Vlach J, Lebecque GT, Bates EEM (2005) Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J Immunol 174:2942–2950

    CAS  PubMed  Google Scholar 

  • Higuchi M, Matsuo A, Shingai M, Shida K, Ishii A, Funami K, Suzuki Y, Oshiumi H, Matsumoto M, Seya T (2008) Combinational recognition of bacterial lipoproteins and peptidoglycan by chicken Toll-like receptor 2 subfamily. Dev Comp Immunol 32:147–155. doi:10.1016/j.dci.2007.05.003

    Article  CAS  PubMed  Google Scholar 

  • Iso-Touro T, Kantanen J, Li MH, Gizejewski Z, Vilkki J (2009) Divergent evolution in the cytoplasmic domains of PRLR and GHR genes in Artiodactyla. BMC Evol Biol 9:172. doi:10.1186/1471-2148-9-172

    Article  Google Scholar 

  • Jann OC, Werling D, Chang JS, Haig D, Glass EJ (2008) Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance. BMC Evol Biol 8:288. doi:10.1186/1471-2148-8-288

    Article  PubMed  Google Scholar 

  • Jann OC, King A, Corrales NL, Anderson SI, Jensen K, Ait-Ali T, Tang H, Wu C, Cockett NE, Archibald AL, Glass EJ (2009) Comparative genomics of Toll-like receptor signaling in five species. BMC Genomics 10:216. doi:10.1186/1471-2164-10-216

    Article  PubMed  Google Scholar 

  • Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO (2007) Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130:1071–1082. doi:10.1016/j.cell.2007.09.008

    Article  CAS  PubMed  Google Scholar 

  • Koradi R, Billeter M, Wüthrich K (1996) MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph 14(51–5):29–32

    Google Scholar 

  • Kruithof EKO, Satta N, Liu JW, Dunoyer-Geindre S, Fish RJ (2007) Gene conversion limits divergence of mammalian TLR1 and TLR6. BMC Evol Biol 7:148. doi:10.1186/1471-2148-7-148

    Article  PubMed  Google Scholar 

  • Kryazhimskiy S, Plotkin JB (2008) The population genetics of dN/dS. PLoS Genetics 4(12):e1000304. doi:10.1371/journal.pgen.1000304

    Article  PubMed  Google Scholar 

  • Larson G, Dobney K, Albarella U, Fang M, Matisoo-Smith E, Robins J, Lowden S, Finlayson H, Brand T, Willerslev E, Rowley-Conwy P, Andersson L, Cooper A (2005) Worldwide phylogeography of wild boar reveals multiple centers of pig domestication. Science 307:1618–1621. doi:10.1126/science.1106927

    Article  CAS  PubMed  Google Scholar 

  • Letunic I, Doerks T, Bork P (2008) SMART 6: recent updates and new developments. Nucleic Acids Res 37:D229–D232. doi:10.1093/nar/gkn808

    Article  PubMed  Google Scholar 

  • Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397. doi:10.1038/41131

    Article  CAS  PubMed  Google Scholar 

  • Megens HJ, Crooijmans RP, San Cristobal M, Hui X, Li N, Groenen MA (2008) Biodiversity of pig breeds from China and Europe estimated from pooled DNA samples: differences in microsatellite variation between two areas of domestication. Genet Sel Evol 40:103–128. doi:10.1051/gse:2007039

    PubMed  Google Scholar 

  • Misch EA, Hawn TR (2008) Toll-like receptor polymorphisms and susceptibility to human disease. Clin Sci (Lond) 114:347–360. doi:10.1042/CS20070214

    Article  Google Scholar 

  • Muneta Y, Uenishi H, Kikuma R, Yoshihara K, Shimoji Y, Yamamoto R, Hamashima N, Yokomizo Y, Mori Y (2003) Porcine TLR2 and TLR6: identification and their involvement in Mycoplasma hyopneumoniae infection. J Interferon Cytokine Res 23:583–590. doi:10.1089/107999003322485080

    Article  CAS  PubMed  Google Scholar 

  • Nakajima T, Ohtani H, Satta Y, Uno Y, Akari H, Ishida T, Kimura A (2008) Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics 60:727–735. doi:10.1007/s00251-008-0332-0

    Article  CAS  PubMed  Google Scholar 

  • Nakamura Y, Gojobori T, Ikemura T (2000) Codon usage tabulated from international DNA sequence databases: status for the year 2000. Nucleic Acids Res 28:292

    Article  CAS  PubMed  Google Scholar 

  • Omueti KO, Beyer JM, Johnson CM, Lyle EA, Tapping RI (2005) Domain exchange between human toll-like receptors 1 and 6 reveals a region required for lipopeptide discrimination. J Biol Chem 280:36616–36625. doi:10.1074/jbc.M504320200

    Article  CAS  PubMed  Google Scholar 

  • Palermo S, Capra E, Torremorell M, Dolzan M, Davoli R, Haley CS, Giuffra E (2009) Toll-like receptor 4 genetic diversity among pig populations. Anim Genet 40:289–299. doi:10.1111/j.1365-2052.2008.01833.x

    Article  CAS  PubMed  Google Scholar 

  • Pamer EG (2007) Immune responses to commensal and environmental microbes. Nat Immunol 8:1173–1178. doi:10.1038/ni1526

    Article  CAS  PubMed  Google Scholar 

  • Peden JF (1999) Analysis of codon usage, Ph.D. Thesis, University of Nottingham, Nottingham

  • Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118:229–241. doi:10.1016/j.cell.2004.07.002

    Article  CAS  PubMed  Google Scholar 

  • Raymond CR, Wilkie BN (2005) Toll-like receptor, MHC II, B7 and cytokine expression by porcine monocytes and monocyte-derived dendritic cells in response to microbial pathogen-associated molecular patterns. Vet Immunol Immunopathol 107:235–247. doi:10.1016/j.vetimm.2005.05.008

    CAS  PubMed  Google Scholar 

  • Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, Hood LE, Aderem A (2005) The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci USA 102:9577–9582. doi:10.1073/pnas.0502272102

    Article  CAS  PubMed  Google Scholar 

  • Shimosato T, Tohno M, Kitazawa H, Katoh S, Watanabe K, Kawai Y, Aso H, Yamaguchi T, Saito T (2005) Toll-like receptor 9 is expressed on follicle-associated epithelia containing M cells in swine Peyer's patches. Immunol Lett 98:83–89. doi:10.1016/j.imlet.2004.10.026

    Article  CAS  PubMed  Google Scholar 

  • Shinkai H, Muneta Y, Suzuki K, Eguchi-Ogawa T, Awata T, Uenishi H (2006a) Porcine Toll-like receptor 1, 6, and 10 genes: complete sequencing of genomic region and expression analysis. Mol Immunol 43:1474–1480. doi:10.1016/j.molimm.2005.09.006

    Article  CAS  PubMed  Google Scholar 

  • Shinkai H, Tanaka M, Morozumi T, Eguchi-Ogawa T, Okumura N, Muneta Y, Awata T, Uenishi H (2006b) Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes. Immunogenetics 58:324–330. doi:10.1007/s00251-005-0068-z

    Article  CAS  PubMed  Google Scholar 

  • Stephan K, Smirnova I, Jacque B, Poltorak A (2007) Genetic analysis of the innate immune responses in wild-derived inbred strains of mice. Eur J Immunol 37:212–223. doi:10.1002/eji.200636156

    Article  CAS  PubMed  Google Scholar 

  • Stephens M, Scheet P (2005) Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet 76:449–462

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13:933–940

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin RL, Akira S (2002) Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14

    CAS  PubMed  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599. doi:10.1093/molbev/msm092

    Article  CAS  PubMed  Google Scholar 

  • Thompson JD, Gibson TJ, Higgins DG (2002) Multiple sequence alignment using ClustalW and ClustalX. Curr Protoc Bioinformatics Chapter 2: Unit 2.3. doi:10.1002/0471250953.bi0203s00

  • Tippmann HF (2004) Analysis for free: comparing programs for sequence analysis. Brief Bioinform 5:82–87

    Article  CAS  PubMed  Google Scholar 

  • Tohno M, Shimosato T, Kitazawa H, Katoh S, Iliev ID, Kimura T, Kawai Y, Watanabe K, Aso H, Yamaguchi T, Saito T (2005) Toll-like receptor 2 is expressed on the intestinal M cells in swine. Biochem Biophys Res Commun 330:547–554. doi:10.1016/j.bbrc.2005.03.017

    Article  CAS  PubMed  Google Scholar 

  • Uenishi H, Shinkai H (2008) Porcine Toll-like receptors: the front line of pathogen monitoring and possible implications for disease resistance. Dev Comp Immunol 33:353–361. doi:10.1016/j.dci.2008.06.001

    Article  PubMed  Google Scholar 

  • Wattrang E, Almqvist M, Johansson A, Fossum C, Wallgren P, Pielberg G, Andersson L, Edfors-Lilja I (2005) Confirmation of QTL on porcine chromosomes 1 and 8 influencing leukocyte numbers, haematological parameters and leukocyte function. Anim Genet 36:337–345. doi:10.1111/j.1365-2052.2005.01315.x

    Article  CAS  PubMed  Google Scholar 

  • Werling D, Jann OC, Offord V, Glass EJ, Coffey TJ (2008) Variation matters: TLR structure and species-specific pathogen recognition. Trends Immunol 30:124–130. doi:10.1016/j.it.2008.12.001

    Article  Google Scholar 

  • Zhong F, Cao W, Chan E, Tay PN, Cahya FF, Zhang H, Lu J (2005) Deviation from major codons in the Toll-like receptor genes is associated with low Toll-like receptor expression. Immunology 114:83–93. doi:10.1111/j.1365-2567.2004.02007.x

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr. Sabine Hammer, University of Veterinary Medicine Vienna, Austria, and Dr. Ales Knoll, Mendel University of Agriculture and Forestry Brno, Czech Republic, for providing us with wild boar DNA. Semen from AI boars was kindly provided by Quality Genetics, Eskilstuna, Sweden. We thank Prof. Kristina Nilsson Ekdahl and Prof. A. Michael Lindberg for fruitful discussions. This work was supported by the Faculty of Natural Science and Technology, Kalmar University, Sweden.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Inger Edfors.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

Fig. S1

(PDF 83 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bergman, IM., Rosengren, J.K., Edman, K. et al. European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes. Immunogenetics 62, 49–58 (2010). https://doi.org/10.1007/s00251-009-0409-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-009-0409-4

Keywords

Navigation