© 2015 Nature America, Inc. All rights reserved. Institute Institute for Evolutionary Anthropology, Leipzig, Germany. should Correspondence be addressed to L.A.F.F. ( California, USA. Laboratory for Archaeology and History of Art, University of Oxford, Oxford, UK. 1 regions core of number limited a from out diffuse forms domesti cated that and rare are episodes domestication that shows that species multiple in origins domestication cally divergent wild populations as of evidence frequent, independent of with multiple, animals geographi domestic affinities phylogenetic interpreted have geneticists model, this under instance, For forms. wild and domestic from data genetic of interpretation the eases tion domestication are well defined. The assumption of reproductive isola of timeframe and origin geographical as the such events key because geneticists for framework theoretical attractive an provides model forms domestic and wild between isolation reproductive and of domestication) beginning at the individuals few a only of selection the to due events founder to (corresponding tion popula in the domestic by humans and strong bottlenecks involving directed being as viewed been often has process this Traditionally, progenitors in wild their to changes comparison in behavioral individuals and domesticated morphological striking to domes led animal of tication process The societies. complex of development the in resulted ultimately which lifestyle, agricultural sedentary a to mal led species to a major shift in from subsistence, a hunter-gatherer of plant the domestication and Revolution, the Neolithic ani During history human in transitions important most the of one was ago, years 10,000 approximately occurred which agriculture, of rise The not major the selection the assumptions whether isolation Traditionally, Yogesh Paudel Laurent A F Frantz domestic pig genomes domestication from analyses of Eurasian wild and Evidence of long-term gene flow and during selection Nature Ge Nature Received 21 November 2014; accepted 10 August 2015; published online 31 August 2015; Animal Animal Breeding and Genomics Group, Wageningen University, Wageningen, the Netherlands. However, this view conflicts with zooarchaeological evidence evidence zooarchaeological with conflicts view this However,

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© 2015 Nature America, Inc. All rights reserved. understand the early understand process we of sampled domestication, a range of ( (ASD; pigs domestic and Asian (ASW) boar of wild Asian populations tiple ( (EUD) breeds domestic historical) or (rare (EUW) non-commercial and boars wild European genomes 103 on from focused analysis Our Asia. and Europe in pigs of domestication the for models multiple of support the Weevaluated RESULTS bottlenecks. strong and isolation reproductive involving domestication of model tional (Western) of domestication Anatolia in pigs restricted geographically single a for data. More generally, we assess whether the zooarchaeological evidence modern the fit better process reticulation a more complex, involving those or explanation linear traditional, a test following to models is whether aim main Our pigs. domestic and wild 100 over from set forms wild and domestic differentiate that traits of maintenance the behind mechanisms the regarding questions raises also pigs domestic and boars wild between flow gene unintentional record zooarchaeological the in as as well animals modern in evident is that pigs domestic and between boars wild dichotomy behavioral and morphological clear a is there tion and is thought to have mainly unintentionally occurred between pigs and wild boars confers no clear advantage to pig produc interbreeding intentional donkeys, and horses with unlike addition, and resolution the of analysis Inby nuclear markers. afforded the large-scale confidence with tested be to yet has pigs in domestication of complex hypothesis the Thus, hypotheses. to these test it impossible making flow, gene of impression limited very a provide markers of because mode of and inheritance limited resolution, mtDNAsmall Moreover, boars. wild from flow gene post-domestication of result domestication of a population of European wild boars rather than the mtDNAthe observed turnovers could also be interpreted as a pigs. domestic of modern genome the in boars wild from flow of gene signal strong a to have left We phenomena such herding. swine expect mobile and was the result of post-domestication gene flow, loose pigpigs management Anatolian and European ancient in replacement mtDNA tion, century nineteenth the in Revolution Industrial the until up selection and management limited as well as evidence, historical and archaeological both with Anatolia and Europe throughout herding swine mobile extensive by were This result suggests replaced European haplotypes. strated that, by 2,500 years before the present, local mtDNA haplotypes domesticated. independently process domestication Anatolian flow the in involved not were gene that populations boar wild from post-domestication experienced populations domestic boar wild European local in found haplotypes mtDNA acquired instead and signatures mtDNA Eastern Near the lost completely had Europe in pigs domestic tion, pigs domestic for evidence logical a single domestication origin of western Eurasian zooarchaeo with concordant present, the before years 7,500 around s e l c i t r A  from boar populations, Asia wild and all major European Pleistocene Supplementary Table1 Supplementary Sus verrucosus Sus

Here we fit models of domestication to a genome-wide data data genome-wide a to domestication of models fit we Here However, although unsupported by any zooarchaeological evidence, demon material Anatolian ancient of analyses mtDNA Further Supplementary Table 1 Supplementary 2 1 ) as an outgroup ( outgroup an as ) . However, a few thousand years after their introduc their after years . However, thousand a few 12 , 13 23 , 2 , 2 1 4 is compatible with the assumption of a tradi a of assumption the with compatible is 12 . Thus, under a complex model of a . domestica model under complex Thus, , ). In addition, the data set comprised mul comprised set data the addition, In ). 2 1 and that European wild boar was not not was boar wild European that and 21 , ). We also included a Javan Wartya pig We). included also 2 2 . These findings suggest that early early that suggest findings These . Supplementary Fig. 1 Fig. Supplementary 6 and European commercial commercial European and 25– 2 8 . Thus, the possibility of of possibility the Thus, . 1 8 . 2 2 ). To better Tobetter ). , consistent , consistent 1 8 de de novo . . Lastly, 2 9 ------

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© 2015 Nature America, Inc. All rights reserved. under a simple model involving human-driven domestication. data pigs from genetic can domestic Thus, modern wild populations. boar domestication. different of mosaic human-driven genetic a are breeds pig involving domestic Instead, expected model be simple would a as group, under genetic homogeneous a constitute of sides both on pigs ( Eurasia domestic and boars wild flow gene between that occurred conclusion our on influence little had populations pig domestic Asian and European between admixture that populations suggests pig domestic between flow gene of amount small this pigs domestic Asian with to admixed be likely less are that breeds domestic European non-commercial on focused Note ASD; and ASW between between wild and domestic populations (between EUW flow and gene EUD and to relative limited very was ASD) and (EUD populations breeds commercial applicable. not NA, Asian; AS, European; EU, model). ghost the without and (with comparison each for model likely most the indicate values Bold (bottom). model ghost the including total, in models seven with computed were second appearing probabilities the and total) in models six (comparing model ghost the without computed were first appearing probabilities the notation, probability posterior the In (bottom). population ghost a and populations domestic and wild the between flow gene with model in displayed are study this in tested models additional four the middle); model; (full populations boar wild between and populations pig domestic between as well as EUD) and (ASD pigs domestic and EUW) and (ASW boars wild between flow gene with one and top) model; (null flow gene without one displayed: are population ghost the including not Two models six the of parameters. continuous independent, two as modeled were that migrations represent arrows Double-headed models. seven or six compared approach 1 Figure Nature Ge Nature c a

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© 2015 Nature America, Inc. All rights reserved. in body length between wild boars and commercial EUD breeds EUD commercial and boars wild between length body in particular, variation in this region explains up to 18% of the difference and in on stature height pigs body strong effect CLR in shown to has EUD) been the highest have (with region This a ( methods haplotype various using region swept this of ( EUD in value CLR highest the with region the of upstream kilobases few a just is region the gene, ( see example, (for interest that ASD seems to have been swept independently and in EUD and ASD EUD 8 Fig. Supplementary between introgression with consistent signal a showed regions these of some of genealogies The ( separately region each in analysis genetic phylo a conducted we signal, significant overlapping an observing ( but ASD and EUW and EUD not ASW in regions in CLR ( value the genome with a significant two the for We selection EUD). and (ASD identified episodes domestication independent parallel of signals for looked we this possibility, investigate To EUD. and ASD both in loci same the at sweeps s e l c i t r A  although although the phenotypic effect of this swept region is still unclear, this Thus, Asia. and Europe in episodes domestication independent two some of convergence the morphological within as well as the between at the same locus. Parallel selection of this form may be responsible for traits in Asian and European domestic pigs resulted in sweeps parallel pigs EUD commercial in morphology for region this of importance the Given genes that influence anatomical and nervous system development, development, system nervous and anatomical influence that genes candidate at selection of evidence extensive shows study Our pigs. domestic in traits behavioral and morphological of maintenance the dogs as as in in (direct, rabbits, versus commensal, pigs and domestication of mode as well as (behavior) specificity biological the with related that the appearance and maintenance of reproductive isolation is cor and horses dogs in suggested was it as taxa, other in hypothesis this test to ies stud future stimulate should here presented flow gene widespread zooarchaeologists by predicted as population is most likely the result of mobile domestic swine herding, quite divergent from the source of domestication. Gene flow from this was that boars of wild population extinct) even (possibly unsampled second a least at involved likely most flow gene Eurasia, western in Moreover,evidence. with the zooarchaeological we demonstrate that, data genetic modern to reconcile is necessary pigs to domestic boars wild from flow gene continuous that shows approach model-testing of evidence a geographically restricted domestication process in pigs. Instead, our zooarchaeological the with incompatible are tlenecks, traditional of such models, as assumptions isolation and reproductive strong bot domestication the that demonstrate we study, this In domestication. animal of understanding greater a and tested be to cal and empirical perspectives are allowing more sophisticated models more fully appreciated. The commensurate advancements in theoreti resolution is allowing the complexity of the domesticationgreater ever with processdata genomic toof amounts be larger of generation The DISCUSSION EUD. and ASD between convergence of possibility the study further to candidate interesting particularly a provides region Fig. Fig.

To rule out admixture between ASD and EUD as the cause for for cause the as EUD and ASD between admixture out rule To Extensive gene flow from wild boars raises questions regarding regarding questions raises boars wild from flow gene Extensive 1 5 5 ). ). Interestingly, although this swept region does not overlap any ) in different domestic species. domestic different in ) 4 Supplementary Figs. 9 Supplementary 1 6 , it is possible that human-mediated selection for similar similar for selection human-mediated that possible is it , 6 . It will be interesting in the future to test the hypothesis hypothesis the to test future in the . interesting Itbe will ). However, we found one region of particular particular of region one However, ). found we Fig. 5 Fig. and 18 , 2 2 10 . The unequivocal evidence of evidence unequivocal The . a ). We validated the presence presence the We validated ). , , and Supplementary Table 4 Supplementary 6 Supplementary Note Supplementary Supplementary Note Supplementary 4 and frequency-based frequency-based and 40 , 4 1 and cattle P < in 0.01) both 42 , 4 3 . . In 4 6 ). 0 ). ). ). ). 5 - - - - - .

role in counteracting the effect of gene flow. Nevertheless, artificial artificial Nevertheless, flow. gene of effect the counteracting in role hypotheses. these test further to means the with studies future provide will that genes of candidate a list highlight results our wild boars or are the result of from selection in variation genetic standing from haplotypes different of selection boars. wild from flow gene However, by it is unclear whether these swept regions involvedaffected recurrent less thus are that traits tic domestication’, which we define as genomic regions selection governing domes of ‘islands genomic artificial created have flow, farmers gene for through allowing but traits similar for selecting recurrently By domestication. pig during place took process analogous an that hypothesize we Here speciation’). of ‘islands genomic (constituting characteristics of species-specific maintenance for the allowed likely and flow gene to resistant be may regions such that suggested have divergence interspecies excessive show that regions genomic identified have common is flow gene which in systems on in allel Asia and Europe. In the context of studies focusing speciation, in par to selection have subject traits been morphological governing domestic pigs. In addition, our results show that regions and close to boars genes wild between observed dichotomy behavioral and logical morpho for the basis genetic the maintained and flow of gene effect homogenizing the counteracted have may selection that suggesting o Note: Any Supplementary Information and Source Data files are available in the accession under (ENA) Archive Nucleotide codes. Accession the t of in version available are references associated any and Methods M process. evolutionary fascinating this of knowledge enhance substantially ultimately will and domestication tion for and involved genes during plants animals but to also identify not only and origin to the time geographical determine of domestica such as the one presented here, will provide the necessary information frameworks, modeling realistic more with DNA, together sequencing ancient of future However, animals. domestic mate and wild genetic from modern rial of analyses comparative conducting when parameters graphical geo and time infer to used be could that signal the of most eroded and likely models of traditional assumptions the violates clearly flow gene extensive Indeed, domestication. during involved genes the ing identify in as well as animals, for domestication of time and origin the determining in models domestication traditional and sequences pigs. domestic and wild between backcrossing adaptive of interbreeding capable pigs domestic of ancestor given range the by Nevertheless, wide geographical occupied the wild boars. wild modern in diversity genetic ancestral of representation introgression in domestic pigs is of because challenging very the poor traits domestic underlying tectures archi in to a genetic the complex assess given broad context difficult mammals domestic diverse horse in blindness night with proposed associated was loci for phenomenon a Such were forms. that wild alleles from of introgressed retention the favored have also may selection nline version of the pape et In this study, in we selection the context only artificial discuss of its Lastly, it is important to underline the limitations of modern DNA Lastly, of modern it the limitations to is important underline h ods he pape he a DVANCE ONLINE PUBLICATION ONLINE DVANCE Raw reads have been deposited in the European European the in deposited been have reads Raw r . r . 71– 7 33 3 . It is therefore important to apply caution caution apply to important therefore It is . , 6 3 as well as the many closely related taxa taxa related closely many the as well as 6 6 , future studies may unravel examples of examples may unravel , studies future 9 . However, such a hypothesis remains remains hypothesis a such However, . 7 0 . Moreover, assessing adaptive adaptive assessing Moreover, . de de novo PRJEB992

6 8 Nature Ge Nature and immunity in in immunity and mutations. Thus, 6 7 . These studies studies These . 2 . n online online etics ------

© 2015 Nature America, Inc. All rights reserved. 24. 23. 22. 21. 20. 19. 18. 17. 16. 15. 14. 13. 12. 11. 10. 9. 8. 7. 6. 5. 4. 3. 2. 1. reprints/index.htm at online available is information permissions and Reprints The authors declare no competing interests.financial all authors. scan. L.A.F.F., J.G.S., G.L. and M.A.M.G. wrote the manuscript with input from J.G.S. performed the modeling. L.A.F.F., J.G.S. and A.C. performed the selection L.A.F.F., H.-J.M., O.M., M.B. and Y.P. andaligned filtered the data. L.A.F.F. and M.A.M.G., L.A.F.F. and G.L. the designed study. R.P.M.A.C. provided the samples. Science Foundation postdoctoral fellowship DBI-1402120. was supported by US National Institutes of Health grant R01-GM40282 and National (SelSweep), grant agreements 249894 and ERC-2013-StG 337574-UNDEAD. J.G.S. European Community’s 256 Seventh Framework Programme (FP7/2007–2013)/ERC This project is financially supported by the European Research Council under the with the figures. We thank B. Dibbits for his help during the laboratory work. for his insights during the conception of the project and D. Caspani for his help for providing us with the latest version of ABCtoolbox. We also thank K. Lohse analysis as well as for kindly sharing his code. We are also indebted to D. WegmannWe thank B. Peter for his help and guidance during the model-fitting step of the Nature Ge Nature COMP AU A c

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© 2015 Nature America, Inc. All rights reserved. simulations that were closest to the observed data and applied a standard standard a applied and approach data ABC-GLM observed the to closest were that simulations data simulated and observed the least- in statistics partial 10 ( extracted Wecomponents (PLS) model. square best-fitting the under simulations ABCtoolbox in as implemented simultaneously libsequence using data simulated and observed ms were computed on statistics Summary model. per simulations we ran 200,000 using performed ( were models seven under recombination with simulations coalescent Backward loci. unlinked 10-kb 100 on performed were Simulations analysis. computation. Bayesian Approximate calls heterozygous of probability the for 0.01 (ref. 2.8 version Analysis UnifiedGenotyper (GATK) Toolkit Genome using called were Variants 10.2. build genome reference to porcine option alignment unique the with (v.1.1.0017) Aligner Mosaik the with than 45 if bp.shorter was performed and discarded Alignment basepairs consecutive three over >20 quality Phred minimum for trimmed were Reads were sequenced to approximately 10× coverage ( coverage 10× approximately to sequenced were calling. variant and Alignment animals culled within wildlife management programs. fromanimalsobtained fromslaughterhouses boar,wildor, of casefrom the in collected by veterinarians according to national legislation or from tissueanalysesdisplayed in samples Note ing kits. The resequencing data were used for modeling (ABC; out on an Illumina HiSeq platform with the 100- and 150-bpaccording paired-endto the Illumina library preparation sequenc protocol. Sequencing was carried preparationLibrary bp). conducted300–500range ofwas size libraries (insert Note displayed in BeadChip. This data set (60K) was solely used for the PCA and TreeMix analyses (Invitrogen). SNP genotyping was performed with itythe and quantityIllumina of the DNA extracted werePorcine60K checked on a Qubit 2.0 fluorometeriSelect from the blood samples with QIAamp DNA Blood Spin kits (Qiagen). The qual full description of the samples, see wild boar tic pigs, 103 European wild boars and 23 Asian wild boars (including a Tibetan total of 622 individuals comprising 403 European domestic pigs,Sample collection92 and AsianDNA domespreparation. ONLINE doi: 10.1038/ng.3394 ). For genome resequencing, we used 1–3 ), the selection scan analyses and the PCA, phylogenyanalysesPCA,selectionscanandthe the ), andADMXITURE 3 6

) and a Javan Warty pig ( MET Supplementary Figures 3, 6 79 H using a standard ABC-GLM general linear model approach approach model linear general ABC-GLM a standard using ODS Figures2 8 2 Supplementary Fig. 2 Fig. Supplementary . Supplementary Fig. 11 Fig. Supplementary and 8 All samples selected for genome sequencing sequencing for genome selected samples All 0 . For parameter inference, we ran 2,000,000 we 2,000,000 ran inference, . For parameter Supplementary Table 1

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