Skip to main content
SpringerLink
Log in

How immunogenetically different are domestic pigs from wild boars: a perspective from single-nucleotide polymorphisms of 19 immunity-related candidate genes

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The coexistence of wild boars and domestic pigs across Eurasia makes it feasible to conduct comparative genetic or genomic analyses for addressing how genetically different a domestic species is from its wild ancestor. To test whether there are differences in patterns of genetic variability between wild and domestic pigs at immunity-related genes and to detect outlier loci putatively under selection that may underlie differences in immune responses, here we analyzed 54 single-nucleotide polymorphisms (SNPs) of 19 immunity-related candidate genes on 11 autosomes in three pairs of wild boar and domestic pig populations from China, Iberian Peninsula, and Hungary. Our results showed no statistically significant differences in allele frequency and heterozygosity across SNPs between three pairs of wild and domestic populations. This observation was more likely due to the widespread and long-lasting gene flow between wild boars and domestic pigs across Eurasia. In addition, we detected eight coding SNPs from six genes as outliers being under selection consistently by three outlier tests (BayeScan2.1, FDIST2, and Arlequin3.5). Among four non-synonymous outlier SNPs, one from TLR4 gene was identified as being subject to positive (diversifying) selection and three each from CD36, IFNW1, and IL1B genes were suggested as under balancing selection. All of these four non-synonymous variants were predicted as being benign by PolyPhen-2. Our results were supported by other independent lines of evidence for positive selection or balancing selection acting on these four immune genes (CD36, IFNW1, IL1B, and TLR4). Our study showed an example applying a candidate gene approach to identify functionally important mutations (i.e., outlier loci) in wild and domestic pigs for subsequent functional experiments.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7:248–9

    Article  PubMed  CAS  Google Scholar 

  • Akey JM (2009) Constructing genomic maps of positive selection in humans: where do we go from here? Genome Res 19:711–722

    Article  PubMed  CAS  Google Scholar 

  • Alves PC, Pinheiro I, Godinho R, Vicente J, Gortazar C, Scandura M (2010) Genetic diversity of wild boar populations and domestic pig breeds (Sus scrofa) in south-western Europe. Biol J Linn Soc 101:797–822

    Article  Google Scholar 

  • Amaral AJ, Ferretti L, Megens H-J, Crooijmans RPMA, Nie H, Ramos-Onsins SE, Perez-Enciso M, Schook LB, Groenen MAM (2011) Genome-wide footprints of pig domestication and selection revealed through massive parallel sequencing of pooled DNA. PLoS One 6:e14782

    Article  PubMed  CAS  Google Scholar 

  • Amos W, Bryant C (2011) Using human demographic history to infer natural selection reveals contrasting patterns on different families of immune genes. Proc R Soc B Biol Sci 278:1587–1594

    Article  Google Scholar 

  • Andersson L (2009) Studying phenotypic evolution in domestic animals: a walk in the footsteps of Charles Darwin. Cold Spring Harb Symp Quant Biol 74:319–325

    Article  PubMed  CAS  Google Scholar 

  • Andrés AM, Hubisz MJ, Indap A, Torgerson DG, Degenhardt JD, Boyko AR, Gutenkunst RN, White TJ, Green ED, Bustamante CD, Clark AG, Nielsen R (2009) Targets of balancing selection in the human genome. Mol Biol Evol 26:2755–2764

    Article  PubMed  Google Scholar 

  • Antao T, Lopes A, Lopes R, Beja-Pereira A, Luikart G (2008) LOSITAN: a workbench to detect molecular adaptation based on a Fst-outlier method. BMC Bioinforma 9:323

    Article  Google Scholar 

  • Axelsson E, Ratnakumar A, Arendt M-L, Maqbool K, Webster MT, Perloski M, Liberg O, Arnemo JM, Hedhammar A, Lindblad-Toh K (2013) The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature 495:360–364

    Article  PubMed  CAS  Google Scholar 

  • Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L (2008) Natural selection has driven population differentiation in modern humans. Nat Genet 40:340–5

    Article  PubMed  CAS  Google Scholar 

  • Barreiro LB, Quintana-Murci L (2010) From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet 11:17–30

    Article  PubMed  CAS  Google Scholar 

  • Beaumont MA, Balding DJ (2004) Identifying adaptive genetic divergence among populations from genome scans. Mol Ecol 13:969–980

    Article  PubMed  CAS  Google Scholar 

  • Beaumont MA, Nichols RA (1996) Evaluating loci for use in the genetic analysis of population structure. Proc R Soc London B 263:1619–1626

    Article  Google Scholar 

  • Bergman I-M, Rosengren J, Edman K, Edfors I (2010) 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

    Article  PubMed  CAS  Google Scholar 

  • Bustamante CD, Fledel-Alon A, Williamson S, Nielsen R, Hubisz MT, Glanowski S, Tanenbaum DM, White TJ, Sninsky JJ, Hernandez RD, Civello D, Adams MD, Cargill M, Clark AG (2005) Natural selection on protein-coding genes in the human genome. Nature 437:1153–7

    Article  PubMed  CAS  Google Scholar 

  • Chen S, Costa V, Beja-Pereira A (2011) Evolutionary patterns of two major reproduction candidate genes (Zp2 and Zp3) reveal no contribution to reproductive isolation between bovine species. BMC Evol Biol 11:24

    Article  PubMed  CAS  Google Scholar 

  • Cornuet JM, Luikart G (1996) Description and power analysis of two tests for detecting recent population bottlenecks from allele frequency data. Genetics 144:2001–2014

    PubMed  CAS  Google Scholar 

  • Earl D, vonHoldt B (2012) STRUCTURE HARVESTER: a website and program for visualizing STRUCTURE output and implementing the Evanno method. Conserv Genet Resour 4:359–361

    Article  Google Scholar 

  • Evanno G, Regnaut S, Goudet J (2005) Detecting the number of clusters of individuals using the software structure: a simulation study. Mol Ecol 14:2611–2620

    Article  PubMed  CAS  Google Scholar 

  • Excoffier L, Hofer T, Foll M (2009) Detecting loci under selection in a hierarchically structured population. Heredity 103:285–298

    Article  PubMed  CAS  Google Scholar 

  • Excoffier L, Lischer HEL (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10:564–567

    Article  PubMed  Google Scholar 

  • Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164:1567–1587

    PubMed  CAS  Google Scholar 

  • Ferrer-Admetlla A, Bosch E, Sikora M, Marquès-Bonet T, Ramírez-Soriano A, Muntasell A, Navarro A, Lazarus R, Calafell F, Bertranpetit J, Casals F (2008) Balancing selection is the main force shaping the evolution of innate immunity genes. J Immunol 181:1315–1322

    PubMed  CAS  Google Scholar 

  • Foll M, Gaggiotti O (2008) A Genome-Scan Method to Identify Selected Loci Appropriate for Both Dominant and Codominant Markers: A Bayesian Perspective. Genetics 180:977–993

    Article  PubMed  Google Scholar 

  • Fumagalli M, Cagliani R, Pozzoli U, Riva S, Comi GP, Menozzi G, Bresolin N, Sironi M (2009) Widespread balancing selection and pathogen-driven selection at blood group antigen genes. Genome Res 19:199–212

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Goedbloed DJ, Megens HJ, Van Hooft P, Herrero-Medrano JM, Lutz W, Alexandri P, Crooijmans RPMA, Groenen M, Van Wieren SE, Ydenberg RC, Prins HHT (2013) Genome-wide single nucleotide polymorphism analysis reveals recent genetic introgression from domestic pigs into Northwest European wild boar populations. Mol Ecol 22:856–866

    Article  PubMed  CAS  Google Scholar 

  • Groenen MAM, Archibald AL, Uenishi H, Tuggle CK, Takeuchi Y, Rothschild MF, Rogel-Gaillard C, Park C, Milan D, Megens H-J, Li S, Larkin DM, Kim H, Frantz LAF, Caccamo M, Ahn H, Aken BL, Anselmo A, Anthon C, Auvil L, Badaoui B, Beattie CW, Bendixen C, Berman D, Blecha F, Blomberg J, Bolund L, Bosse M, Botti S, Bujie Z, Bystrom M, Capitanu B, Carvalho-Silva D, Chardon P, Chen C, Cheng R, Choi S-H, Chow W, Clark RC, Clee C, Crooijmans RPMA, Dawson HD, Dehais P, De Sapio F, Dibbits B, Drou N, Du Z-Q, Eversole K, Fadista J, Fairley S, Faraut T, Faulkner GJ, Fowler KE, Fredholm M, Fritz E, Gilbert JGR, Giuffra E, Gorodkin J, Griffin DK, Harrow JL, Hayward A, Howe K, Hu Z-L, Humphray SJ, Hunt T, Hornshoj H, Jeon J-T, Jern P, Jones M, Jurka J, Kanamori H, Kapetanovic R, Kim J, Kim J-H, Kim K-W, Kim T-H, Larson G, Lee K, Lee K-T, Leggett R, Lewin HA, Li Y, Liu W, Loveland JE, Lu Y, Lunney JK, Ma J, Madsen O, Mann K, Matthews L, McLaren S, Morozumi T, Murtaugh MP, Narayan J, Truong Nguyen D, Ni P, Oh S-J, Onteru S, Panitz F, Park E-W et al (2012) Analyses of pig genomes provide insight into porcine demography and evolution. Nature 491:393–398

    Article  PubMed  CAS  Google Scholar 

  • Hofer T, Foll M, Excoffier L (2012) Evolutionary forces shaping genomic islands of population differentiation in humans. BMC Genomics 13:107

    Article  PubMed  CAS  Google Scholar 

  • Ji Y-Q, Wu D-D, Wu G-S, Wang G-D, Zhang Y-P (2011) Multi-locus analysis reveals a different pattern of genetic diversity for mitochondrial and nuclear DNA between wild and domestic pigs in East Asia. PLoS One 6:e26416

    Article  PubMed  CAS  Google Scholar 

  • Kosiol C, Vinař T, da Fonseca RR, Hubisz MJ, Bustamante CD, Nielsen R, Siepel A (2008) Patterns of positive selection in six mammalian genomes. PLoS Genet 4:e1000144

    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

    Article  PubMed  CAS  Google Scholar 

  • Leffler EM, Gao Z, Pfeifer S, Ségurel L, Auton A, Venn O, Bowden R, Bontrop R, Wall JD, Sella G, Donnelly P, McVean G, Przeworski M (2013) Multiple instances of ancient balancing selection shared between humans and chimpanzees. Science 339:1578–1582

    Article  PubMed  CAS  Google Scholar 

  • Manunza A, Zidi A, Yeghoyan S, Balteanu VA, Carsai TC, Scherbakov O, Ramírez O, Eghbalsaied S, Castelló A, Mercadé A, Amills M (2013) A high throughput genotyping approach reveals distinctive autosomal genetic signatures for European and near eastern wild boar. PLoS One 8:e55891

    Article  PubMed  CAS  Google Scholar 

  • Megens H-J, Crooijmans R, Cristobal M, Hui X, Li N, Groenen M (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

    PubMed  Google Scholar 

  • Morcillo-Suarez C, Alegre J, Sangros R, Gazave E, de Cid R, Milne R, Amigo J, Ferrer-Admetlla A, Moreno-Estrada A, Gardner M, Casals F, Pérez-Lezaun A, Comas D, Bosch E, Calafell F, Bertranpetit J, Navarro A (2008) SNP analysis to results (SNPator): a web-based environment oriented to statistical genomics analyses upon SNP data. Bioinformatics 24:1643–1644

    Article  PubMed  CAS  Google Scholar 

  • Narum SR, Hess JE (2011) Comparison of FST outlier tests for SNP loci under selection. Mol Ecol Resour 11:184–194

    Article  PubMed  Google Scholar 

  • Peakall R, Smouse PE (2012) GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research—an update. Bioinformatics 28:2537–9

    Article  PubMed  CAS  Google Scholar 

  • Price EO (2002) Animal domestication and behavior. CABI, Wallingford

    Book  Google Scholar 

  • Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959

    PubMed  CAS  Google Scholar 

  • Ramírez O, Ojeda A, Tomàs A, Gallardo D, Huang LS, Folch JM, Clop A, Sánchez A, Badaoui B, Hanotte O, Galman-Omitogun O, Makuza SM, Soto H, Cadillo J, Kelly L, Cho IC, Yeghoyan S, Pérez-Enciso M, Amills M (2009) Integrating Y-chromosome, mitochondrial, and autosomal data to analyze the origin of pig breeds. Mol Biol Evol 26:2061–2072

    Article  PubMed  Google Scholar 

  • Rehfeldt C, Henning M, Fiedler I (2008) Consequences of pig domestication for skeletal muscle growth and cellularity. Livest Sci 116:30–41

    Article  Google Scholar 

  • Reiner G, Bronnert B, Hohloch C, Fresen C, Haack I, Willems H, Reinacher M (2010) Qualitative and quantitative distribution of PCV2 in wild boars and domestic pigs in Germany. Vet Microbiol 145:1–8

    Article  PubMed  Google Scholar 

  • Rosenberg NA (2004) Distruct: a program for the graphical display of population structure. Mol Ecol Notes 4:137–138

    Article  Google Scholar 

  • Ross-Ibarra J, Morrell PL, Gaut BS (2007) Plant domestication, a unique opportunity to identify the genetic basis of adaptation. P Natl Acad Sci U S A 104:8641–8648

    Article  CAS  Google Scholar 

  • Rubin C-J, Megens H-J, Barrio AM, Maqbool K, Sayyab S, Schwochow D, Wang C, Carlborg Ö, Jern P, Jørgensen CB, Archibald AL, Fredholm M, Groenen MAM, Andersson L (2012) Strong signatures of selection in the domestic pig genome. Proc Natl Acad Sci 109:19529–19536

    Article  PubMed  CAS  Google Scholar 

  • Rubin C-J, Zody MC, Eriksson J, Meadows JRS, Sherwood E, Webster MT, Jiang L, Ingman M, Sharpe T, Ka S, Hallbook F, Besnier F, Carlborg O, Bed/'hom B, Tixier-Boichard M, Jensen P, Siegel P, Lindblad-Toh K, Andersson L (2010) Whole-genome resequencing reveals loci under selection during chicken domestication. Nature 464:587–591

    Article  PubMed  CAS  Google Scholar 

  • Sabeti PC, Schaffner SF, Fry B, Lohmueller J, Varilly P, Shamovsky O, Palma A, Mikkelsen TS, Altshuler D, Lander ES (2006) Positive natural selection in the human lineage. Science 312:1614–1620

    Article  PubMed  CAS  Google Scholar 

  • Scandura M, Iacolina L, Crestanello B, Pecchioli E, Di Benedetto MF, Russo V, Davoli R, Apollonio M, Bertorelle G (2008) Ancient vs. recent processes as factors shaping the genetic variation of the European wild boar: are the effects of the last glaciation still detectable? Mol Ecol 17:1745–1762

    Article  PubMed  CAS  Google Scholar 

  • Smouse PE, Peakall R (1999) Spatial autocorrelation analysis of individual multiallele and multilocus genetic structure. Hered (Edinb) 82(Pt 5):561–73

    Article  Google Scholar 

  • Stephan W, Song YS, Langley CH (2006) The hitchhiking effect on linkage disequilibrium between linked neutral loci. Genetics 172:2647–2663

    Article  PubMed  CAS  Google Scholar 

  • The International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437:1299–1320

    Article  Google Scholar 

  • Turner AK, Begon M, Jackson JA, Bradley JE, Paterson S (2011) Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population. PLoS Genet 7:e1002343

    Article  PubMed  CAS  Google Scholar 

  • Turner AK, Begon M, Jackson JA, Paterson S (2012) Evidence for selection at cytokine loci in a natural population of field voles (Microtus agrestis). Mol Ecol 21:1632–1646

    Article  PubMed  CAS  Google Scholar 

  • van Asch B, Pereira F, Santos LS, Carneiro J, Santos N, Amorim A (2012) Mitochondrial lineages reveal intense gene flow between Iberian wild boars and South Iberian pig breeds. Anim Genet 43:35–41

    Article  PubMed  Google Scholar 

  • vonHoldt BM, Pollinger JP, Lohmueller KE, Han E, Parker HG, Quignon P, Degenhardt JD, Boyko AR, Earl DA, Auton A, Reynolds A, Bryc K, Brisbin A, Knowles JC, Mosher DS, Spady TC, Elkahloun A, Geffen E, Pilot M, Jedrzejewski W, Greco C, Randi E, Bannasch D, Wilton A, Shearman J, Musiani M, Cargill M, Jones PG, Qian Z, Huang W, Ding Z-L, Y-p Z, Bustamante CD, Ostrander EA, Novembre J, Wayne RK (2010) Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature 464:898–902

    Article  PubMed  CAS  Google Scholar 

  • Weir BS, Cockerham CC (1984) Estimating F-statistics for the analysis of population structure. Evolution 38:1358–1370

    Article  Google Scholar 

  • White SN, Taylor KH, Abbey CA, Gill CA, Womack JE (2003) Haplotype variation in bovine Toll-like receptor 4 and computational prediction of a positively selected ligand-binding domain. P Natl Acad Sci U S A 100:10364–10369

    Article  CAS  Google Scholar 

  • Wilkinson S, Lu ZH, Megens H-J, Archibald AL, Haley C, Jackson IJ, Groenen MAM, Crooijmans RPMA, Ogden R, Wiener P (2013) Signatures of diversifying selection in European pig breeds. PLoS Genet 9:e1003453

    Article  PubMed  CAS  Google Scholar 

  • Wlasiuk G, Nachman MW (2010) Adaptation and constraint at toll-like receptors in primates. Mol Biol Evol 27:2172–2186

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank two anonymous reviewers for their constructive comments. This work was financially supported by Fundação para a Ciência e Tecnologia (FCT) projects PTDC/CVT/68907/2006 (ABP) and PTDC/CVT/099782/2008 (SC). SC is supported by FCT individual grant SFRH/BPD/46082/2008.

Conflicting interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Centro de Investigação em Biodiversidade e Recursos Genéticos da Universidade do Porto (CIBIO/UP), Campus Agrário de Vairão, Rua Padre Armando Quintas 7, 4485-661, Vairão, Portugal

    Shanyuan Chen, Rui Gomes, Vânia Costa & Albano Beja-Pereira

  2. ICAAM – Instituto de Ciências Agrárias e Ambientais Mediterrânicas, Universidade de Évora, Herdade da Mitra, 7002-554, Évora, Portugal

    Pedro Santos, Rui Charneca & Jose-Luis Nunes

  3. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China

    Ya-ping Zhang

  4. Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming, 650091, China

    Ya-ping Zhang

  5. Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, 650201, China

    Xue-hong Liu & Shao-qing Wang

  6. Associação Nacional de Criadores de Porco Alentejano (ANCPA), 7350, Elvas, Portugal

    Pedro Bento

  7. SEFAG Forest Management and Wood Industry Share Company, Kaposvár, Hungary

    József Buzgó & Gyula Varga

  8. Research Institute for Animal Breeding and Nutrition, 2053, Herceghalom, Hungary

    István Anton & Attila Zsolnai

  9. University of Kaposvár, 7400, Kaposvár, Hungary

    Attila Zsolnai

Authors
  1. Shanyuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vânia Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pedro Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rui Charneca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ya-ping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xue-hong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shao-qing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pedro Bento
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jose-Luis Nunes
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. József Buzgó
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gyula Varga
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. István Anton
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Attila Zsolnai
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Albano Beja-Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Albano Beja-Pereira.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Table S1

– PCR and sequencing primers of 13 candidate genes (PDF 23 kb)

Table S2

– List of SNPs discovered by sequencing a 16-sample panel (PDF 59 kb)

Table S3

– List of 64 SNPs from 19 candidate genes genotyped (PDF 57 kb)

Table S4

– List of 54 SNPs finally analyzed and their summary statistics (PDF 42 kb)

Figure S1

– Plotting Delta K against the numbers of clusters (K = 1 to 10) by STRUCTURE HARVESTER using Evanno method indicated that K = 3 best fits the data (PDF 52 kb)

Figure S2

– The outliers detected by Arlequin3.5 hierarchical island model at three groups (Chinese vs. Iberian vs. Hungarian populations) (PDF 43 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, S., Gomes, R., Costa, V. et al. How immunogenetically different are domestic pigs from wild boars: a perspective from single-nucleotide polymorphisms of 19 immunity-related candidate genes. Immunogenetics 65, 737–748 (2013). https://doi.org/10.1007/s00251-013-0718-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-013-0718-5

Keywords

Search

Navigation