Skip to main content
SpringerLink
Log in

DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds

  • Original Article
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf. Altogether, 79 CpG sites constituting the 65 so-called CpG units located in the promoter regions of genes affecting behavioral and temperamental traits (COMT, HTR1A, MAOA, OXTR, SLC6A4, TPH1, WFS1)—regions putatively targeted during domestication and breed selection. Methylation status of buccal cells was assessed using EpiTYPER technology. Significant inter-population methylation differences were found in 52.3% of all CpG units investigated. DNA methylation profile-based hierarchical cluster analysis indicated an unambiguous segregation of wolf from domestic dog. In addition, one of the three dog breeds (Golden Retriever) investigated also formed a separate, autonomous group. The findings support that population segregation is interrelated with shifts in DNA methylation patterns, at least in putative selection target regions, and also imply that epigenetic profiles could provide a sufficient basis for population assignment of individuals.

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

Similar content being viewed by others

References

  • Aguilera O, Fernandez AF, Munoz A, Fraga MF (2010) Epigenetics and environment: a complex relationship. J Appl Physiol (1985) 109:243–251

    Article  CAS  Google Scholar 

  • Aken BL, Ayling S, Barrell D, Clarke L, Curwen V, Fairley S, Fernandez Banet J, Billis K, Garcia Giron C, Hourlier T, Howe K, Kahari A, Kokocinski F, Martin FJ, Murphy DN, Nag R, Ruffier M, Schuster M, Tang YA, Vogel JH, White S, Zadissa A, Flicek P, Searle SM (2016) The Ensembl gene annotation system. Database 2016: baw093

    Article  PubMed  PubMed Central  Google Scholar 

  • Aken BL, Achuthan P, Akanni W, Amode MR, Bernsdorff F, Bhai J, Billis K, Carvalho-Silva D, Cummins C, Clapham P, Gil L, Giron CG, Gordon L, Hourlier T, Hunt SE, Janacek SH, Juettemann T, Keenan S, Laird MR, Lavidas I, Maurel T, McLaren W, Moore B, Murphy DN, Nag R, Newman V, Nuhn M, Ong CK, Parker A, Patricio M, Riat HS, Sheppard D, Sparrow H, Taylor K, Thormann A, Vullo A, Walts B, Wilder SP, Zadissa A, Kostadima M, Martin FJ, Muffato M, Perry E, Ruffier M, Staines DM, Trevanion SJ, Cunningham F, Yates A, Zerbino DR, Flicek P (2017) Ensembl 2017. Nucleic Acids Res 45:D635–D642

    Article  PubMed  Google Scholar 

  • Albert FW, Somel M, Carneiro M, Aximu-Petri A, Halbwax M, Thalmann O, Blanco-Aguiar JA, Plyusnina IZ, Trut L, Villafuerte R, Ferrand N, Kaiser S, Jensen P, Paabo S (2012) A comparison of brain gene expression levels in domesticated and wild animals. PLoS Genet 8:e1002962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Axelsson E, Ratnakumar A, Arendt ML, 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  CAS  PubMed  Google Scholar 

  • Bai B, Zhao WM, Tang BX, Wang YQ, Wang L, Zhang Z, Yang HC, Liu YH, Zhu JW, Irwin DM, Wang GD, Zhang YP (2015) DoGSD: the dog and wolf genome SNP database. Nucleic Acids Res 43:D777–D783

    Article  PubMed  Google Scholar 

  • Bale TL (2015) Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 16:332–344

    Article  CAS  PubMed  Google Scholar 

  • Boor K, Ronai Z, Nemoda Z, Gaszner P, Sasvari-Szekely M, Guttman A, Kalasz H (2002) Noninvasive genotyping of dopamine receptor D4 (DRD4) using nanograms of DNA from substance-dependent patients. Curr Med Chem 9:793–797

    Article  CAS  PubMed  Google Scholar 

  • Careau V, Reale D, Humphries MM, Thomas DW (2010) The pace of life under artificial selection: personality, energy expenditure, and longevity are correlated in domestic dogs. Am Nat 175:753–758

    Article  PubMed  Google Scholar 

  • Chagnon YC, Potvin O, Hudon C, Preville M (2015) DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women. Front Genet 6:230

    Article  PubMed  PubMed Central  Google Scholar 

  • Consortium EP (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74

    Article  Google Scholar 

  • Couldrey C, Lee RS (2010) DNA methylation patterns in tissues from mid-gestation bovine foetuses produced by somatic cell nuclear transfer show subtle abnormalities in nuclear reprogramming. BMC Dev Biol 10:27

    Article  PubMed  PubMed Central  Google Scholar 

  • Daxinger L, Whitelaw E (2010) Transgenerational epigenetic inheritance: more questions than answers. Genome Res 20:1623–1628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Falco M, Manente L, Lucariello A, Baldi G, Fiore P, Laforgia V, Baldi A, Iannaccone A, De Luca A (2012) Localization and distribution of wolframin in human tissues. Front Biosci (Elite Ed) 4:1986–1998

    Article  Google Scholar 

  • Ding ZL, Oskarsson M, Ardalan A, Angleby H, Dahlgren LG, Tepeli C, Kirkness E, Savolainen P, Zhang YP (2012) Origins of domestic dog in southern East Asia is supported by analysis of Y-chromosome DNA. Heredity (Edinb) 108:507–514

    Article  CAS  Google Scholar 

  • Dolinoy DC (2008) The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev 66(Suppl 1):S7–S11

    Article  PubMed  PubMed Central  Google Scholar 

  • Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, van den Boom D (2005) Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci USA 102:15785–15790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eo J, Lee HE, Nam GH, Kwon YJ, Choi Y, Choi BH, Huh JW, Kim M, Lee SE, Seo B, Kim HS (2016) Association of DNA methylation and monoamine oxidase A gene expression in the brains of different dog breeds. Gene 580:177–182

    Article  CAS  PubMed  Google Scholar 

  • Farre D, Roset R, Huerta M, Adsuara JE, Rosello L, Alba MM, Messeguer X (2003) Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN. Nucleic Acids Res 31:3651–3653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feil R, Fraga MF (2011) Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 13:97–109

    Google Scholar 

  • Freedman AH, Gronau I, Schweizer RM, Ortega-Del Vecchyo D, Han E, Silva PM, Galaverni M, Fan Z, Marx P, Lorente-Galdos B, Beale H, Ramirez O, Hormozdiari F, Alkan C, Vila C, Squire K, Geffen E, Kusak J, Boyko AR, Parker HG, Lee C, Tadigotla V, Wilton A, Siepel A, Bustamante CD, Harkins TT, Nelson SF, Ostrander EA, Marques-Bonet T, Wayne RK, Novembre J (2014) Genome sequencing highlights the dynamic early history of dogs. PLoS Genet 10:e1004016

    Article  PubMed  PubMed Central  Google Scholar 

  • Fukuda K, Ichiyanagi K, Yamada Y, Go Y, Udono T, Wada S, Maeda T, Soejima H, Saitou N, Ito T, Sasaki H (2013) Regional DNA methylation differences between humans and chimpanzees are associated with genetic changes, transcriptional divergence and disease genes. J Hum Genet 58:446–454

    Article  CAS  PubMed  Google Scholar 

  • Gainetdinov RR, Caron MG (2003) Monoamine transporters: from genes to behavior. Annu Rev Pharmacol Toxicol 43:261–284

    Article  CAS  PubMed  Google Scholar 

  • Gaydos LJ, Wang W, Strome S (2014) Gene repression. H3K27me and PRC2 transmit a memory of repression across generations and during development. Science 345:1515–1518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Germonpre M, Sablin MV, Stevens RE, Hedges REM, Hofreiter M, Stiller M, Despres VR (2009) Fossil dogs and wolves from Palaeolithic sites in Belgium, the Ukraine and Russia: osteometry, ancient DNA and stable isotopes. J Arch Sci 36:473–490

    Article  Google Scholar 

  • Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA (2009) Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 7:62

    Article  PubMed  PubMed Central  Google Scholar 

  • Hannon E, Lunnon K, Schalkwyk L, Mill J (2015) Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes. Epigenetics 10:1024–1032

    Article  PubMed  PubMed Central  Google Scholar 

  • Harony-Nicolas H, Mamrut S, Brodsky L, Shahar-Gold H, Barki-Harrington L, Wagner S (2014) Brain region-specific methylation in the promoter of the murine oxytocin receptor gene is involved in its expression regulation. Psychoneuroendocrinology 39:121–131

    Article  CAS  PubMed  Google Scholar 

  • Horvath S, Zhang Y, Langfelder P, Kahn RS, Boks MP, van Eijk K, van den Berg LH, Ophoff RA (2012) Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol 13:R97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Illingworth RS, Gruenewald-Schneider U, De Sousa D, Webb S, Merusi C, Kerr AR, James KD, Smith C, Walker R, Andrews R, Bird AP (2015) Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome. Nucleic Acids Res 43:732–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jack A, Connelly JJ, Morris JP (2012) DNA methylation of the oxytocin receptor gene predicts neural response to ambiguous social stimuli. Front Hum Neurosci 6:280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janowitz Koch I, Clark MM, Thompson MJ, Deere-Machemer KA, Wang J, Duarte L, Gnanadesikan GE, McCoy EL, Rubbi L, Stahler DR, Pellegrini M, Ostrander EA, Wayne RK, Sinsheimer JS, vonHoldt BM (2016) The concerted impact of domestication and transposon insertions on methylation patterns between dogs and grey wolves. Mol Ecol 25:1838–1855

    Article  CAS  PubMed  Google Scholar 

  • Jensen P (2015) Adding ‘epi-’ to behaviour genetics: implications for animal domestication. J Exp Biol 218:32–40

    Article  PubMed  Google Scholar 

  • Kato T, Ishiwata M, Yamada K, Kasahara T, Kakiuchi C, Iwamoto K, Kawamura K, Ishihara H, Oka Y (2008) Behavioral and gene expression analyses of Wfs1 knockout mice as a possible animal model of mood disorder. Neurosci Res 61:143–158

    Article  CAS  PubMed  Google Scholar 

  • Kozlenkov A, Wang M, Roussos P, Rudchenko S, Barbu M, Bibikova M, Klotzle B, Dwork AJ, Zhang B, Hurd YL, Koonin EV, Wegner M, Dracheva S (2016) Substantial DNA methylation differences between two major neuronal subtypes in human brain. Nucleic Acids Res 44:2593–2612

    Article  PubMed  Google Scholar 

  • Kukekova AV, Johnson JL, Teiling C, Li L, Oskina IN, Kharlamova AV, Gulevich RG, Padte R, Dubreuil MM, Vladimirova AV, Shepeleva DV, Shikhevich SG, Sun Q, Ponnala L, Temnykh SV, Trut LN, Acland GM (2011) Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes). BMC Genomics 12:482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kusui C, Kimura T, Ogita K, Nakamura H, Matsumura Y, Koyama M, Azuma C, Murata Y (2001) DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression. Biochem Biophys Res Commun 289:681–686

    Article  CAS  PubMed  Google Scholar 

  • LaPlant Q, Vialou V, Covington HE 3rd, Dumitriu D, Feng J, Warren BL, Maze I, Dietz DM, Watts EL, Iniguez SD, Koo JW, Mouzon E, Renthal W, Hollis F, Wang H, Noonan MA, Ren Y, Eisch AJ, Bolanos CA, Kabbaj M, Xiao G, Neve RL, Hurd YL, Oosting RS, Fan G, Morrison JH, Nestler EJ (2010) Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci 13:1137–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lesch KP (2007) Linking emotion to the social brain. The role of the serotonin transporter in human social behaviour. EMBO Rep 8:S24–S29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Vonholdt BM, Reynolds A, Boyko AR, Wayne RK, Wu DD, Zhang YP (2013) Artificial selection on brain-expressed genes during the domestication of dog. Mol Biol Evol 30:1867–1876

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Wang Y, Hu X, Zhao Y, Li N (2015) Genome-wide mapping reveals conservation of promoter DNA methylation following chicken domestication. Sci Rep 5:8748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lokk K, Modhukur V, Rajashekar B, Martens K, Magi R, Kolde R, Koltsina M, Nilsson TK, Vilo J, Salumets A, Tonisson N (2014) DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns. Genome Biol 15:r54

    Article  PubMed  PubMed Central  Google Scholar 

  • Lowe R, Slodkowicz G, Goldman N, Rakyan VK (2015) The human blood DNA methylome displays a highly distinctive profile compared with other somatic tissues. Epigenetics 10:274–281

    Article  PubMed  PubMed Central  Google Scholar 

  • Martin DI, Singer M, Dhahbi J, Mao G, Zhang L, Schroth GP, Pachter L, Boffelli D (2011) Phyloepigenomic comparison of great apes reveals a correlation between somatic and germline methylation states. Genome Res 21:2049–2057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathelier A, Fornes O, Arenillas DJ, Chen CY, Denay G, Lee J, Shi W, Shyr C, Tan G, Worsley-Hunt R, Zhang AW, Parcy F, Lenhard B, Sandelin A, Wasserman WW (2016) JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles. Nucleic Acids Res 44:D110–D115

    Article  PubMed  Google Scholar 

  • McGreevy PD, Georgevsky D, Carrasco J, Valenzuela M, Duffy DL, Serpell JA (2013) Dog behavior co-varies with height, bodyweight and skull shape. PLoS ONE 8:e80529

    Article  PubMed  PubMed Central  Google Scholar 

  • Mendizabal I, Shi L, Keller TE, Konopka G, Preuss TM, Hsieh TF, Hu E, Zhang Z, Su B, Yi SV (2016) Comparative methylome analyses identify epigenetic regulatory loci of human brain evolution. Mol Biol Evol 33:2947–2959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messeguer X, Escudero R, Farre D, Nunez O, Martinez J, Alba MM (2002) PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics 18:333–334

    Article  CAS  PubMed  Google Scholar 

  • Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J, Felsberg J, Kahl P, Buttner R, Pietsch T, Waha A (2007) Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 9:368–381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869

    Article  CAS  PubMed  Google Scholar 

  • Miller CA, Campbell SL, Sweatt JD (2008) DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiol Learn Mem 89:599–603

    Article  CAS  PubMed  Google Scholar 

  • Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A, Yancey CR, Rivera IM, Rubio MD, Rumbaugh G, Sweatt JD (2010) Cortical DNA methylation maintains remote memory. Nat Neurosci 13:664–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molaro A, Hodges E, Fang F, Song Q, McCombie WR, Hannon GJ, Smith AD (2011) Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell 146:1029–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura K, Sugawara Y, Sawabe K, Ohashi A, Tsurui H, Xiu Y, Ohtsuji M, Lin QS, Nishimura H, Hasegawa H, Hirose S (2006) Late developmental stage-specific role of tryptophan hydroxylase 1 in brain serotonin levels. J Neurosci 26:530–534

    Article  CAS  PubMed  Google Scholar 

  • Natt D, Rubin CJ, Wright D, Johnsson M, Belteky J, Andersson L, Jensen P (2012) Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens. BMC Genomics 13:59

    Article  PubMed  PubMed Central  Google Scholar 

  • Neumann ID (2008) Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 20:858–865

    Article  CAS  PubMed  Google Scholar 

  • Pai AA, Bell JT, Marioni JC, Pritchard JK, Gilad Y (2011) A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues. PLoS Genet 7:e1001316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parker HG (2012) Genomic analyses of modern dog breeds. Mamm Genome 23:19–27

    Article  PubMed  PubMed Central  Google Scholar 

  • Parle-McDermott A, Ozaki M (2011) The impact of nutrition on differential methylated regions of the genome. Adv Nutr 2:463–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28:1057–1068

    Article  CAS  PubMed  Google Scholar 

  • Ptacek R, Kuzelova H, Stefano GB (2011) Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders. Med Sci Monit 17:RA215–R220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandelin A, Alkema W, Engstrom P, Wasserman WW, Lenhard B (2004) JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res 32:D91–D94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Savolainen P, Zhang YP, Luo J, Lundeberg J, Leitner T (2002) Genetic evidence for an East Asian origin of domestic dogs. Science 298:1610–1613

    Article  CAS  PubMed  Google Scholar 

  • Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308–311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shih JC, Chen K, Ridd MJ (1999) Monoamine oxidase: from genes to behavior. Annu Rev Neurosci 22:197–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skinner MK, Guerrero-Bosagna C, Haque MM (2015) Environmentally induced epigenetic transgenerational inheritance of sperm epimutations promote genetic mutations. Epigenetics 10:762–771

    Article  PubMed  PubMed Central  Google Scholar 

  • Smith AK, Kilaru V, Klengel T, Mercer KB, Bradley B, Conneely KN, Ressler KJ, Binder EB (2015) DNA extracted from saliva for methylation studies of psychiatric traits: evidence tissue specificity and relatedness to brain. Am J Med Genet B 168B:36–44

    Article  Google Scholar 

  • Smith TA, Martin MD, Nguyen M, Mendelson TC (2016) Epigenetic divergence as a potential first step in darter speciation. Mol Ecol 25:1883–1894

    Article  CAS  PubMed  Google Scholar 

  • Solnica-Krezel L, Sepich DS (2012) Gastrulation: making and shaping germ layers. Annu Rev Cell Dev Biol 28:687–717

    Article  CAS  PubMed  Google Scholar 

  • Sommer-Trembo C, Bierbach D, Arias-Rodriguez L, Verel Y, Jourdan J, Zimmer C, Riesch R, Streit B, Plath M (2016) Does personality affect premating isolation between locally-adapted populations? BMC Evol Biol 16:138

    Article  PubMed  PubMed Central  Google Scholar 

  • Szyf M (2011) DNA methylation, the early-life social environment and behavioral disorders. J Neurodev Disord 3:238–249

    Article  PubMed  PubMed Central  Google Scholar 

  • Thalmann O, Shapiro B, Cui P, Schuenemann VJ, Sawyer SK, Greenfield DL, Germonpre MB, Sablin MV, Lopez-Giraldez F, Domingo-Roura X, Napierala H, Uerpmann HP, Loponte DM, Acosta AA, Giemsch L, Schmitz RW, Worthington B, Buikstra JE, Druzhkova A, Graphodatsky AS, Ovodov ND, Wahlberg N, Freedman AH, Schweizer RM, Koepfli KP, Leonard JA, Meyer M, Krause J, Paabo S, Green RE, Wayne RK (2013) Complete mitochondrial genomes of ancient canids suggest a European origin of domestic dogs. Science 342:871–874

    Article  CAS  PubMed  Google Scholar 

  • Thierry-Mieg D, Thierry-Mieg J (2006) AceView: a comprehensive cDNA-supported gene and transcripts annotation. Genome Biol 7(Suppl 1):S12 11–14

  • Thompson TM, Sharfi D, Lee M, Yrigollen CM, Naumova OY, Grigorenko EL (2013) Comparison of whole-genome DNA methylation patterns in whole blood, saliva, and lymphoblastoid cell lines. Behav Genet 43:168–176

    Article  PubMed  Google Scholar 

  • Turner BM (2009) Epigenetic responses to environmental change and their evolutionary implications. Philos Trans R Soc Lond B Biol Sci 364:3403–3418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unternaehrer E, Luers P, Mill J, Dempster E, Meyer AH, Staehli S, Lieb R, Hellhammer DH, Meinlschmidt G (2012) Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Transl Psychiatry 2:e150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unternaehrer E, Meyer AH, Burkhardt SC, Dempster E, Staehli S, Theill N, Lieb R, Meinlschmidt G (2015) Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women. Stress 18:451–461

    Article  PubMed  Google Scholar 

  • Vage J, Bonsdorff TB, Arnet E, Tverdal A, Lingaas F (2010) Differential gene expression in brain tissues of aggressive and non-aggressive dogs. BMC Vet Res 6:34

    Article  PubMed  PubMed Central  Google Scholar 

  • Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, Cross MK, Williams BA, Stamatoyannopoulos JA, Crawford GE, Absher DM, Wold BJ, Myers RM (2013) Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res 23:555–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verzijden MN, ten Cate C, Servedio MR, Kozak GM, Boughman JW, Svensson EI (2012) The impact of learning on sexual selection and speciation. Trends Ecol Evol 27:511–519

    Article  PubMed  Google Scholar 

  • Vila C, Amorim IR, Leonard JA, Posada D, Castroviejo J, Petrucci-Fonseca F, Crandall KA, Ellegren H, Wayne RK (1999) Mitochondrial DNA phylogeography and population history of the grey wolf canis lupus. Mol Ecol 8:2089–2103

    Article  CAS  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 ZL, Zhang YP, 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  CAS  PubMed  PubMed Central  Google Scholar 

  • Walton E, Hass J, Liu J, Roffman JL, Bernardoni F, Roessner V, Kirsch M, Schackert G, Calhoun V, Ehrlich S (2016) Correspondence of DNA methylation between blood and brain tissue and its application to schizophrenia research. Schizophr Bull 42:406–414

    Article  PubMed  Google Scholar 

  • Wang GD, Zhai W, Yang HC, Wang L, Zhong L, Liu YH, Fan RX, Yin TT, Zhu CL, Poyarkov AD, Irwin DM, Hytonen MK, Lohi H, Wu CI, Savolainen P, Zhang YP (2016) Out of southern East Asia: the natural history of domestic dogs across the world. Cell Res 26:21–33

    Article  PubMed  Google Scholar 

  • Wayne RK, vonHoldt BM (2012) Evolutionary genomics of dog domestication. Mamm Genome 23:3–18

    Article  PubMed  Google Scholar 

  • Weinshilboum RM, Otterness DM, Szumlanski CL (1999) Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu Rev Pharmacol Toxicol 39:19–52

    Article  CAS  PubMed  Google Scholar 

  • Xing Y, Shi S, Le L, Lee CA, Silver-Morse L, Li WX (2007) Evidence for transgenerational transmission of epigenetic tumor susceptibility in Drosophila. PLoS Genet 3:1598–1606

    Article  CAS  PubMed  Google Scholar 

  • Yu NK, Baek SH, Kaang BK (2011) DNA methylation-mediated control of learning and memory. Mol Brain 4:5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was funded by the National Scientific Fund of Hungary (Grant numbers OTKA ANN 107726 and OTKA K 112138), the Austrian Science Fund (Grant number FWF I 1271-B24), and the Vienna Science and Technology Fund (Grant number WWTF CS11-026). Eniko Kubinyi was supported by the Bolyai Foundation. The authors would like to thank Peter Marx for providing help with wolf sequence data collection and analysis.

Author information

Authors and Affiliations

  1. Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Tűzoltó utca 37-47, Budapest, 1094, Hungary

    Zsofia Banlaki, Maria Sasvari-Szekely & Zsolt Ronai

  2. Comparative Cognition, Messerli Research Institute, University of Veterinary Medicine, Vienna, Medical University of Vienna, University of Vienna, Veterinärplatz 1, 1210, Vienna, Austria

    Giulia Cimarelli & Zsofia Viranyi

  3. Wolf Science Center, Dörfles 48, 2115, Ernstbrunn, Austria

    Giulia Cimarelli & Zsofia Viranyi

  4. Department of Cognitive Biology, University of Vienna, Althanstrasse 14, 1190, Vienna, Austria

    Giulia Cimarelli

  5. MTA-ELTE Comparative Ethology Research Group, Hungarian Academy of Sciences, Pázmány Péter sétány 1/C, Budapest, 1117, Hungary

    Eniko Kubinyi

  6. Department of Ethology, Eötvös Loránd University, Pázmány Péter sétány 1/C, Budapest, 1117, Hungary

    Eniko Kubinyi

Authors
  1. Zsofia Banlaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giulia Cimarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zsofia Viranyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eniko Kubinyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Sasvari-Szekely
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zsolt Ronai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zsofia Banlaki.

Ethics declarations

Conflict of interest

All the authors declare no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

Additional information

Communicated by S. Hohmann.

Electronic supplementary material

Below is the link to the electronic supplementary material.

438_2017_1305_MOESM1_ESM.tif

Supplementary Fig. 1: Percent methylation of amplicons with p = 0.0001 inter-population differences in the four populations investigated. Methylation values for each individual animal are indicated. Horizontal lines represent mean values ± SD (standard deviation) (TIF 42932 KB)

Supplementary Table 1 (DOC 47 KB)

Supplementary Table 2 (DOC 103 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Banlaki, Z., Cimarelli, G., Viranyi, Z. et al. DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds. Mol Genet Genomics 292, 685–697 (2017). https://doi.org/10.1007/s00438-017-1305-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-017-1305-5

Keywords

Search

Navigation