Ancient Epigenomics

Part of the Population Genomics book series (POGE)


Recent molecular and computational advances in ancient DNA research have revealed that genome-scale epigenetic information can be retrieved from subfossil material. In fact, it appears that particular features of the chromatin, and its regulatory epigenetic marks at the time of death, are preserved within ancient DNA extracts. The characterization of this additional layer of information, which represents an interface between the genome and the environment and is not coded within modifications of the DNA sequence itself, opens new horizons for ancient DNA research. At the individual level, ancient epigenetic marks can provide novel molecular phenotypes of the age at death, diet restriction, and other stress conditions, including sociocultural changes. At the population level, they can complement classical inference based on genetic information to reveal the regulatory changes underlying divergence, speciation, and extinction. Exploiting such information will nonetheless be challenging, due to the nature of epigenetic data, which can vary across cell types, tissues, sex, and age, and be significantly influenced by genetic variation and environmental exposure.


Ancient DNA Cytosine deamination DNA methylation Epigenome Nucleosome protection 


  1. Allentoft ME, Collins M, Harker D, et al. The half-life of DNA in bone: measuring decay kinetics in 158 dated fossils. Proc Biol Sci. 2012;279:4724–33. Scholar
  2. Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet. 2016;17:487–500. Scholar
  3. Allum F, Shao X, Guénard F, et al. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants. Nat Commun. 2015;6:7211. Scholar
  4. AlQahtani SJ, Hector MP, Liversidge HM. Accuracy of dental age estimation charts: Schour and Massler, Ubelaker and the London Atlas. Am J Phys Anthropol. 2014;154:70–8. Scholar
  5. Andersson L, Archibald AL, Bottema CD, et al. Coordinated international action to accelerate genome-to-phenome with FAANG, the functional annotation of animal genomes project. Genome Biol. 2015;16:57. Scholar
  6. Anway MD, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors. Endocrinology. 2006;147:S43–9. Scholar
  7. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308:1466–9. Scholar
  8. Bai L, Morozov AV. Gene regulation by nucleosome positioning. Trends Genet. 2010;26:476–83. Scholar
  9. Ball MP, Li JB, Gao Y, et al. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27:361–8. Scholar
  10. Bauer T, Trump S, Ishaque N, et al. Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children. Mol Syst Biol. 2016;12:861.CrossRefGoogle Scholar
  11. Bell JT, Pai AA, Pickrell JK, et al. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol. 2011a;12:R10. Scholar
  12. Bell O, Tiwari VK, Thomä NH, Schübeler D. Determinants and dynamics of genome accessibility. Nat Rev Genet. 2011b;12:554–64. Scholar
  13. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009;23:781–3. Scholar
  14. Bernstein BE, Stamatoyannopoulos JA, Costello JF, et al. The NIH roadmap epigenomics mapping consortium. Nat Biotechnol. 2010;28:1045–8. Scholar
  15. Bird A. Perceptions of epigenetics. Nat Lond. 2007;447:396–8. Scholar
  16. Boyko A, Kovalchuk I. Genetic and epigenetic effects of plant-pathogen interactions: an evolutionary perspective. Mol Plant. 2011;4:1014–23. Scholar
  17. Boyko A, Kathiria P, Zemp FJ, et al. Transgenerational changes in the genome stability and methylation in pathogen-infected plants: (virus-induced plant genome instability). Nucleic Acids Res. 2007;35:1714–25. Scholar
  18. Braud M, Magee DA, Park SDE, et al. Genome-wide microRNA binding site variation between extinct wild aurochs and modern cattle identifies candidate microRNA-regulated domestication genes. Front Genet. 2017;8:3. Scholar
  19. Briggs AW, Stenzel U, Johnson PLF, et al. Patterns of damage in genomic DNA sequences from a Neandertal. Proc Natl Acad Sci U S A. 2007;104:14616–21. Scholar
  20. Briggs AW, Stenzel U, Meyer M, et al. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res. 2010;38:e87. Scholar
  21. Brogaard K, Xi L, Wang J-P, Widom J. A map of nucleosome positions in yeast at base-pair resolution. Nature. 2012;486:496–501. Scholar
  22. Brooks S, Suchey JM. Skeletal age determination based on the os pubis: a comparison of the Acsádi-Nemeskéri and Suchey-Brooks methods. Hum Evol. 1990;5:227–38. Scholar
  23. Buckley M, Walker A, Ho SYW, et al. Comment on “Protein sequences from mastodon and Tyrannosaurus rex revealed by mass spectrometry”. Science. 2008;319:33. Author reply 33.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Carpenter ML, Buenrostro JD, Valdiosera C, et al. Pulling out the 1%: whole-genome capture for the targeted enrichment of ancient DNA sequencing libraries. Am J Hum Genet. 2013;93:852–64. Scholar
  25. Castillo-Fernandez JE, Spector TD, Bell JT. Epigenetics of discordant monozygotic twins: implications for disease. Genome Med. 2014;6:60. Scholar
  26. Chen Q, Yan W, Duan E. Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet. 2016;17:733–43. Scholar
  27. Chodavarapu RK, Feng S, Bernatavichute YV, et al. Relationship between nucleosome positioning and DNA methylation. Nature. 2010;466:388–92. Scholar
  28. Chua EYD, Vasudevan D, Davey GE, et al. The mechanics behind DNA sequence-dependent properties of the nucleosome. Nucleic Acids Res. 2012;40:6338–52. Scholar
  29. Collins LJ, Schönfeld B, Chen XS. The epigenetics of non-coding RNA. In: Tollefsbol T, editor. Handbook of epigenetics: the new molecular and medical genetics. London: Academic; 2011. p. 49–61.CrossRefGoogle Scholar
  30. Cruz-Dávalos DI, Llamas B, Gaunitz C, et al. Experimental conditions improving in solution target enrichment for ancient DNA. Mol Ecol Resour. 2016;17(3):508–22. Scholar
  31. Dabney J, Meyer M. Length and GC-biases during sequencing library amplification: a comparison of various polymerase-buffer systems with ancient and modern DNA sequencing libraries. BioTechniques. 2012;52:87–94. Scholar
  32. Dabney J, Knapp M, Glocke I, et al. Complete mitochondrial genome sequence of a middle Pleistocene cave bear reconstructed from ultrashort DNA fragments. Proc Natl Acad Sci U S A. 2013;110:15758–63. Scholar
  33. Damgaard PB, Margaryan A, Schroeder H, et al. Improving access to endogenous DNA in ancient bones and teeth. Sci Rep. 2015;5:11184. Scholar
  34. Danchin É, Charmantier A, Champagne FA, et al. Beyond DNA: integrating inclusive inheritance into an extended theory of evolution. Nat Rev Genet. 2011;12:475–86. Scholar
  35. Daniel FI, Cherubini K, Yurgel LS, et al. The role of epigenetic transcription repression and DNA methyltransferases in cancer. Cancer. 2011;117:677–87. Scholar
  36. Davis AP, Capecchi MR. Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11. Development. 1994;120:2187–98.PubMedGoogle Scholar
  37. Daxinger L, Whitelaw E. Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet. 2012;13:153–62. Scholar
  38. de Rooij SR, Painter RC, Phillips DIW, et al. Impaired insulin secretion after prenatal exposure to the Dutch famine. Diabetes Care. 2006;29:1897–901. Scholar
  39. de Rooij SR, Wouters H, Yonker JE, et al. Prenatal undernutrition and cognitive function in late adulthood. Proc Natl Acad Sci U S A. 2010;107:16881–6. Scholar
  40. Deans C, Maggert KA. What do you mean, “epigenetic”? Genetics. 2015;199:887–96. Scholar
  41. Demarchi B, Hall S, Roncal-Herrero T, et al. Protein sequences bound to mineral surfaces persist into deep time. elife. 2016;5:e17092. Scholar
  42. Der Sarkissian C, Ermini L, Jónsson H, et al. Shotgun microbial profiling of fossil remains. Mol Ecol. 2014;23:1780–98. Scholar
  43. Der Sarkissian C, Allentoft ME, Ávila-Arcos MC, et al. Ancient genomics. Philos Trans R Soc Lond Ser B Biol Sci. 2015a;370:20130387. Scholar
  44. Der Sarkissian C, Ermini L, Schubert M, et al. Evolutionary genomics and conservation of the endangered Przewalski’s horse. Curr Biol. 2015b;25:2577–83. Scholar
  45. Dolinoy DC. The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev. 2008;66:S7–S11. Scholar
  46. Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect. 2006;114:567–72.CrossRefGoogle Scholar
  47. Dolinoy DC, Huang D, Jirtle RL. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A. 2007;104:13056–61. Scholar
  48. Down TA, Rakyan VK, Turner DJ, et al. A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nat Biotechnol. 2008;26:779–85. Scholar
  49. Eckhardt F, Lewin J, Cortese R, et al. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet. 2006;38:1378–85. Scholar
  50. Ehrlich M, Gama-Sosa MA, Huang LH, et al. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res. 1982;10:2709–21.CrossRefGoogle Scholar
  51. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74. Scholar
  52. Ermini L, Der Sarkissian C, Willerslev E, Orlando L. Major transitions in human evolution revisited: a tribute to ancient DNA. J Hum Evol. 2015;79:4–20. Scholar
  53. Fagny M, Patin E, MacIsaac JL, et al. The epigenomic landscape of African rainforest hunter-gatherers and farmers. Nat Commun. 2015;6:10047. Scholar
  54. Favier B, Meur ML, Chambon P, Dollé P. Axial skeleton homeosis and forelimb malformations in Hoxd-11 mutant mice. Proc Natl Acad Sci. 1995;92:310–4.CrossRefGoogle Scholar
  55. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13:97–109. Scholar
  56. Fordyce SL, Kampmann M-L, van Doorn NL, Gilbert MTP. Long-term RNA persistence in postmortem contexts. Investig Genet. 2013;4:7. Scholar
  57. Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005;102:10604–9. Scholar
  58. Frantz LAF, Schraiber JG, Madsen O, et al. Evidence of long-term gene flow and selection during domestication from analyses of Eurasian wild and domestic pig genomes. Nat Genet. 2015;47:1141–8. Scholar
  59. Fraser HB, Lam LL, Neumann SM, Kobor MS. Population-specificity of human DNA methylation. Genome Biol. 2012;13:R8. Scholar
  60. Fu Y, Sinha M, Peterson CL, Weng Z. The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome. PLoS Genet. 2008;4:e1000138. Scholar
  61. Galanter JM, Gignoux CR, Oh SS, et al. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures. elife. 2017;6:e20532. Scholar
  62. Gamba C, Hanghøj K, Gaunitz C, et al. Comparing the performance of three ancient DNA extraction methods for high-throughput sequencing. Mol Ecol Resour. 2016;16:459–69. Scholar
  63. Gansauge M-T, Meyer M. Single-stranded DNA library preparation for the sequencing of ancient or damaged DNA. Nat Protoc. 2013;8:737–48. Scholar
  64. Gansauge M-T, Meyer M. Selective enrichment of damaged DNA molecules for ancient genome sequencing. Genome Res. 2014;24:1543–9. Scholar
  65. Gehring M. Prodigious plant methylomes. Genome Biol. 2016;17:197. Scholar
  66. Giuliani C, Cilli E, Bacalini MG, et al. Inferring chronological age from DNA methylation patterns of human teeth. Am J Phys Anthropol. 2015;159(4):585–95. Scholar
  67. Gokhman D, Lavi E, Prüfer K, et al. Reconstructing the DNA methylation maps of the Neandertal and the Denisovan. Science. 2014;344:523–7. Scholar
  68. Gokhman D, Meshorer E, Carmel L. Epigenetics: it’s getting old. Past meets future in Paleoepigenetics. Trends Ecol Evol. 2016;31(4):290–300. Scholar
  69. Gokhman D, Agranat-Tamir L, Housman G, et al. Recent regulatory changes shaped human facial and vocal anatomy. bioRxiv. 2017;106955.
  70. Green RE, Krause J, Ptak SE, et al. Analysis of one million base pairs of Neanderthal DNA. Nature. 2006;444:330–6. Scholar
  71. Grunau C, Clark SJ, Rosenthal A. Bisulfite genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res. 2001;29:E65.CrossRefGoogle Scholar
  72. Gu H, Smith ZD, Bock C, et al. Preparation of reduced representation bisulfite sequencing libraries for genome-scale DNA methylation profiling. Nat Protoc. 2011;6:468–81. Scholar
  73. Haak W, Lazaridis I, Patterson N, et al. Massive migration from the steppe was a source for Indo-European languages in Europe. Nature. 2015;522:207–11. Scholar
  74. Hackett JA, Surani MA. Beyond DNA: programming and inheritance of parental methylomes. Cell. 2013;153:737–9. Scholar
  75. Hackman DA, Farah MJ, Meaney MJ. Socioeconomic status and the brain: mechanistic insights from human and animal research. Nat Rev Neurosci. 2010;11:651–9. Scholar
  76. Hanghøj K, Seguin-Orlando A, Schubert M, et al. Fast, accurate and automatic ancient nucleosome and methylation maps with epiPALEOMIX. Mol Biol Evol. 2016;33(12):3284–98. Scholar
  77. Hansen A, Willerslev E, Wiuf C, et al. Statistical evidence for miscoding lesions in ancient DNA templates. Mol Biol Evol. 2001;18:262–5.CrossRefGoogle Scholar
  78. He Y, Ecker JR. Non-CG methylation in the human genome. Annu Rev Genomics Hum Genet. 2015;16:55–77. Scholar
  79. Heard E, Martienssen RA. Transgenerational epigenetic inheritance: myths and mechanisms. Cell. 2014;157:95–109. Scholar
  80. Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008;105:17046–9. Scholar
  81. Heyn H, Moran S, Hernando-Herraez I, et al. DNA methylation contributes to natural human variation. Genome Res. 2013;23:1363–72. Scholar
  82. Ho S-M, Johnson A, Tarapore P, et al. Environmental epigenetics and its implication on disease risk and health outcomes. ILAR J. 2012;53:289–305. Scholar
  83. Hofreiter M, Jaenicke V, Serre D, et al. DNA sequences from multiple amplifications reveal artifacts induced by cytosine deamination in ancient DNA. Nucleic Acids Res. 2001a;29:4793–9.CrossRefGoogle Scholar
  84. Hofreiter M, Serre D, Poinar HN, et al. Ancient DNA. Nat Rev Genet. 2001b;2:353–9. Scholar
  85. Holoch D, Moazed D. RNA-mediated epigenetic regulation of gene expression. Nat Rev Genet. 2015;16:71–84. Scholar
  86. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115. Scholar
  87. Horvath S, Gurven M, Levine ME, et al. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Genome Biol. 2016;17:171. Scholar
  88. Houseman EA, Accomando WP, Koestler DC, et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012;13:86. Scholar
  89. Jin H, Rube HT, Song JS. Categorical spectral analysis of periodicity in nucleosomal DNA. Nucleic Acids Res. 2016;44(5):2047–57. Scholar
  90. Jónsson H, Ginolhac A, Schubert M, et al. mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters. Bioinformatics. 2013;29:1682–4. Scholar
  91. Jónsson H, Schubert M, Seguin-Orlando A, et al. Speciation with gene flow in equids despite extensive chromosomal plasticity. Proc Natl Acad Sci U S A. 2014;111:18655–60. Scholar
  92. Keller A, Graefen A, Ball M, et al. New insights into the Tyrolean Iceman’s origin and phenotype as inferred by whole genome sequencing. Nat Commun. 2012;3:698.CrossRefGoogle Scholar
  93. Kelly TK, Liu Y, Lay FD, et al. Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules. Genome Res. 2012;22:2497–506. Scholar
  94. Kelman Z, Moran L. Degradation of ancient DNA. Curr Biol. 1996;6:223.CrossRefGoogle Scholar
  95. Knights D, Kuczynski J, Charlson ES, et al. Bayesian community-wide culture-independent microbial source tracking. Nat Methods. 2011;8:761–3. Scholar
  96. Kogan SB, Kato M, Kiyama R, Trifonov EN. Sequence structure of human nucleosome DNA. J Biomol Struct Dyn. 2006;24:43–8. Scholar
  97. Kousathanas A, Leuenberger C, Link V, et al. Inferring heterozygosity from ancient and low coverage genomes. Genetics. 2017;205:317–32. Scholar
  98. Krueger F, Kreck B, Franke A, Andrews SR. DNA methylome analysis using short bisulfite sequencing data. Nat Methods. 2012;9:145–51. Scholar
  99. Lam LL, Emberly E, Fraser HB, et al. Factors underlying variable DNA methylation in a human community cohort. Proc Natl Acad Sci U S A. 2012;109(Suppl 2):17253–60. Scholar
  100. Lazaridis I, Patterson N, Mittnik A, et al. Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature. 2014;513:409–13. Scholar
  101. Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell. 2007;128:707–19. Scholar
  102. Librado P, Der Sarkissian C, Ermini L, et al. Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments. Proc Natl Acad Sci U S A. 2015;112:E6889–97. Scholar
  103. Librado P, Gamba C, Gaunitz C, et al. Ancient genomic changes associated with domestication of the horse. Science. 2017;356:442–5. Scholar
  104. Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993;362:709–15. Scholar
  105. Lister R, Ecker JR. Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res. 2009;19:959–66. Scholar
  106. Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315–22. Scholar
  107. Liu H, Liu X, Zhang S, et al. Systematic identification and annotation of human methylation marks based on bisulfite sequencing methylomes reveals distinct roles of cell type-specific hypomethylation in the regulation of cell identity genes. Nucleic Acids Res. 2016;44:75–94. Scholar
  108. Llamas B, Holland ML, Chen K, et al. High-resolution analysis of cytosine methylation in ancient DNA. PLoS One. 2012;7:e30226. Scholar
  109. Llamas B, Willerslev E, Orlando L. Human evolution: a tale from ancient genomes. Philos Trans R Soc Lond Ser B Biol Sci. 2017;372:1713. Scholar
  110. Louvel G, Der Sarkissian C, Hanghøj K, Orlando L. metaBIT, an integrative and automated metagenomic pipeline for analysing microbial profiles from high-throughput sequencing shotgun data. Mol Ecol Resour. 2016;16:1415–27. Scholar
  111. Lumey LH, Stein AD, Kahn HS, et al. Cohort profile: the Dutch Hunger winter families study. Int J Epidemiol. 2007;36:1196–204. Scholar
  112. Lynch VJ, Bedoya-Reina OC, Ratan A, et al. Elephantid genomes reveal the molecular bases of Woolly Mammoth adaptations to the arctic. Cell Rep. 2015;12:217–28. Scholar
  113. Marciniak S, Perry GH. Harnessing ancient genomes to study the history of human adaptation. Nat Rev Genet. 2017;18(11):659–74. Scholar
  114. Marioni RE, Shah S, McRae AF, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015;16:25. Scholar
  115. Mathieson I, Lazaridis I, Rohland N, et al. Eight thousand years of natural selection in Europe. 2015.
  116. Maunakea AK, Nagarajan RP, Bilenky M, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466:253–7. Scholar
  117. McGowan PO, Sasaki A, D’Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12:342–8. Scholar
  118. Meyer M, Kircher M. Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb Protoc. 2010;2010:db.prot5448. Scholar
  119. Meyer M, Kircher M, Gansauge M-T, et al. A high-coverage genome sequence from an archaic Denisovan individual. Science. 2012;338:222–6. Scholar
  120. Miller W, Drautz DI, Ratan A, et al. Sequencing the nuclear genome of the extinct woolly mammoth. Nature. 2008;456:387–90. Scholar
  121. Miller W, Schuster SC, Welch AJ, et al. Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change. PNAS. 2012;109(36):E2382–90. Scholar
  122. Monge I, Kondo T, Duboule D. An enhancer-titration effect induces digit-specific regulatory alleles of the HoxD cluster. Dev Biol. 2003;256:212–20.CrossRefGoogle Scholar
  123. Morey C, Avner P. Genetics and epigenetics of the X chromosome. Ann N Y Acad Sci. 2010;1214:E18–33. Scholar
  124. Murgatroyd C, Patchev AV, Wu Y, et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci. 2009;12:1559–66. Scholar
  125. Murray IA, Clark TA, Morgan RD, et al. The methylomes of six bacteria. Nucleic Acids Res. 2012;40:11450–62. Scholar
  126. Nielsen R, Akey JM, Jakobsson M, et al. Tracing the peopling of the world through genomics. Nature. 2017;541:302–10. Scholar
  127. Orlando L, Willerslev E. Evolution. An epigenetic window into the past? Science. 2014;345:511–2. Scholar
  128. Orlando L, Ginolhac A, Zhang G, et al. Recalibrating Equus evolution using the genome sequence of an early middle Pleistocene horse. Nature. 2013;499:74–8. Scholar
  129. Orlando L, Gilbert MTP, Willerslev E. Reconstructing ancient genomes and epigenomes. Nat Rev Genet. 2015;16:395–408. Scholar
  130. Painter RC, de Rooij SR, Bossuyt PM, et al. Early onset of coronary artery disease after prenatal exposure to the Dutch famine. Am J Clin Nutr. 2006;84:322–7.CrossRefGoogle Scholar
  131. Painter RC, Osmond C, Gluckman P, et al. Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG Int J Obstet Gynaecol. 2008;115:1243–9. Scholar
  132. Palkopoulou E, Mallick S, Skoglund P, et al. Complete genomes reveal signatures of demographic and genetic declines in the woolly mammoth. Curr Biol. 2015;25:1395–400. Scholar
  133. Park SDE, Magee DA, McGettigan PA, et al. Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle. Genome Biol. 2015;16:234. Scholar
  134. Patin E, Laval G, Barreiro LB, et al. Inferring the demographic history of African farmers and pygmy hunter-gatherers using a multilocus resequencing data set. PLoS Genet. 2009;5:e1000448. Scholar
  135. Pedersen JS, Valen E, Velazquez AMV, et al. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome. Genome Res. 2014;24:454–66. Scholar
  136. Pembrey M, Saffery R, Bygren LO, et al. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research. J Med Genet. 2014;51:563–72. Scholar
  137. Petropoulos S, Panula SP, Schell JP, Lanner F. Single-cell RNA sequencing: revealing human pre-implantation development, pluripotency and germline development. J Intern Med. 2016;280:252–64. Scholar
  138. Pinhasi R, Fernandes D, Sirak K, et al. Optimal ancient DNA yields from the inner ear part of the human petrous bone. PLoS One. 2015;10:e0129102. Scholar
  139. Plongthongkum N, Diep DH, Zhang K. Advances in the profiling of DNA modifications: cytosine methylation and beyond. Nat Rev Genet. 2014;15:647–61. Scholar
  140. Pokholok DK, Harbison CT, Levine S, et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell. 2005;122:517–27. Scholar
  141. Portales-Casamar E, Lussier AA, Jones MJ, et al. DNA methylation signature of human fetal alcohol spectrum disorder. Epigenetics Chromatin. 2016;9:25. Scholar
  142. Prüfer K, Racimo F, Patterson N, et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature. 2014;505:43–9. Scholar
  143. Quail MA, Kozarewa I, Smith F, et al. A large genome center’s improvements to the Illumina sequencing system. Nat Methods. 2008;5:1005–10. Scholar
  144. Racimo F, Gokhman D, Fumagalli M, et al. Archaic adaptive introgression in TBX15/WARS2. Mol Biol Evol. 2016;34(3):509–24. Scholar
  145. Radford EJ, Ito M, Shi H, et al. In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science. 2014;345:1255903. Scholar
  146. Rakyan VK, Down TA, Balding DJ, Beck S. Epigenome-wide association studies for common human diseases. Nat Rev Genet. 2011;12:529–41. Scholar
  147. Ramakrishnan V. Histone structure and the organization of the nucleosome. Annu Rev Biophys Biomol Struct. 1997;26:83–112. Scholar
  148. Ramos-Madrigal J, Smith BD, Moreno-Mayar JV, et al. Genome sequence of a 5,310-year-old maize cob provides insights into the early stages of maize domestication. Curr Biol. 2016;26:3195–201. Scholar
  149. Rasmussen M, Li Y, Lindgreen S, et al. Ancient human genome sequence of an extinct Palaeo-Eskimo. Nature. 2010;463:757–62. Scholar
  150. Rasmussen M, Anzick SL, Waters MR, et al. The genome of a late Pleistocene human from a Clovis burial site in western Montana. Nature. 2014;506:225–9. Scholar
  151. Rebelo AP, Williams SL, Moraes CT. In vivo methylation of mtDNA reveals the dynamics of protein-mtDNA interactions. Nucleic Acids Res. 2009;37:6701–15. Scholar
  152. Rhee I, Jair KW, Yen RW, et al. CpG methylation is maintained in human cancer cells lacking DNMT1. Nature. 2000;404:1003–7. Scholar
  153. Richards EJ. Inherited epigenetic variation – revisiting soft inheritance. Nat Rev Genet. 2006;7:395–401. Scholar
  154. Rohland N, Harney E, Mallick S, et al. Partial uracil-DNA-glycosylase treatment for screening of ancient DNA. Philos Trans R Soc Lond Ser B Biol Sci. 2015;370:20130624. Scholar
  155. Roseboom T, de Rooij S, Painter R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006;82:485–91. Scholar
  156. Ross MG, Russ C, Costello M, et al. Characterizing and measuring bias in sequence data. Genome Biol. 2013;14:R51. Scholar
  157. Schubert M, Jónsson H, Chang D, et al. Prehistoric genomes reveal the genetic foundation and cost of horse domestication. Proc Natl Acad Sci U S A. 2014;111:E5661–9. Scholar
  158. Schweitzer MH, Suo Z, Avci R, et al. Analyses of soft tissue from Tyrannosaurus rex suggest the presence of protein. Science. 2007;316:277–80. Scholar
  159. Schweitzer MH, Zheng W, Organ CL, et al. Biomolecular characterization and protein sequences of the Campanian hadrosaur B. canadensis. Science. 2009;324:626–31. Scholar
  160. Schweitzer MH, Schroeter ER, Goshe MB. Protein molecular data from ancient (>1 million years old) fossil material: pitfalls, possibilities and grand challenges. Anal Chem. 2014;86:6731–40. Scholar
  161. Seguin-Orlando A, Gamba C, Der Sarkissian C, et al. Pros and cons of methylation-based enrichment methods for ancient DNA. Sci Rep. 2015a;5:11826. Scholar
  162. Seguin-Orlando A, Hoover CA, Vasiliev SK, et al. Amplification of TruSeq ancient DNA libraries with AccuPrime Pfx: consequences on nucleotide misincorporation and methylation patterns. Sci Technol Archaeol Res. 2015b;1(1):1–9.Google Scholar
  163. Skoglund P, Ersmark E, Palkopoulou E, Dalén L. Ancient wolf genome reveals an early divergence of domestic dog ancestors and admixture into high-latitude breeds. Curr Biol. 2015;25:1515–9. Scholar
  164. Slotkin RK, Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet. 2007;8:272–85. Scholar
  165. Smith O, Clapham A, Rose P, et al. A complete ancient RNA genome: identification, reconstruction and evolutionary history of archaeological Barley Stripe Mosaic Virus. Sci Rep. 2014a;4:4003. Scholar
  166. Smith O, Clapham AJ, Rose P, et al. Genomic methylation patterns in archaeological barley show de-methylation as a time-dependent diagenetic process. Sci Rep. 2014b;4:5559. Scholar
  167. Smith RWA, Monroe C, Bolnick DA. Detection of cytosine methylation in ancient DNA from five native american populations using bisulfite sequencing. PLoS One. 2015;10:e0125344. Scholar
  168. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–5. Scholar
  169. Struhl K, Segal E. Determinants of nucleosome positioning. Nat Struct Mol Biol. 2013;20:267–73. Scholar
  170. Susser E, Kirkbride JB, Heijmans BT, et al. Maternal prenatal nutrition and health in grandchildren and subsequent generations. Annu Rev Anthropol. 2012;41:577–610. Accessed 28 Feb 2017.CrossRefGoogle Scholar
  171. Taudt A, Colomé-Tatché M, Johannes F. Genetic sources of population epigenomic variation. Nat Rev Genet. 2016;17:319–32. Scholar
  172. Tobi EW, Lumey LH, Talens RP, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009;18:4046–53. Scholar
  173. Triantaphyllopoulos KA, Ikonomopoulos I, Bannister AJ. Epigenetics and inheritance of phenotype variation in livestock. Epigenetics Chromatin. 2016;9:31. Scholar
  174. Valouev A, Johnson SM, Boyd SD, et al. Determinants of nucleosome organization in primary human cells. Nature. 2011;474:516–20. Scholar
  175. Waddington CH. The epigenotype. Endeavour. 1942;1:18–20.Google Scholar
  176. Weber M, Davies JJ, Wittig D, et al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet. 2005;37:853–62. Scholar
  177. Zhang W, Spector TD, Deloukas P, et al. Predicting genome-wide DNA methylation using methylation marks, genomic position, and DNA regulatory elements. Genome Biol. 2015;16:14. Scholar
  178. Ziller MJ, Gu H, Müller F, et al. Charting a dynamic DNA methylation landscape of the human genome. Nature. 2013;500:477–81. Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Centre for GeoGeneticsNatural History Museum of DenmarkCopenhagenDenmark
  2. 2.Laboratoire AMIS, CNRS UMR 5288Université de Toulouse, Université Paul Sabatier (UPS)ToulouseFrance

Personalised recommendations