Improved detection of methylation in ancient DNA.

DNA Methylation DNA, Ancient / analysis Humans Sulfites Sequence Analysis, DNA / methods
Ancient DNA Bisulfite treatment Enzymatic methylation treatment Methylation Paleogenomics

Journal

Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660

Informations de publication

Date de publication:
10 Oct 2024
Historique:
received: 20 12 2023
accepted: 26 09 2024
medline: 11 10 2024
pubmed: 11 10 2024
entrez: 10 10 2024
Statut: epublish

Résumé

Reconstructing premortem DNA methylation levels in ancient DNA has led to breakthrough studies such as the prediction of anatomical features of the Denisovan. These studies rely on computationally inferring methylation levels from damage signals in naturally deaminated cytosines, which requires expensive high-coverage genomes. Here, we test two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. Bisulfite treatment shows the least reduction in DNA yields as well as the least biases during methylation conversion, demonstrating that this method can be successfully applied to ancient DNA.

Identifiants

DOI: 10.1186/s13059-024-03405-5 PMID: 39390557
pubmed: 39390557
doi: 10.1186/s13059-024-03405-5
pii: 10.1186/s13059-024-03405-5
doi:

Substances chimiques

DNA, Ancient 0
Sulfites 0
hydrogen sulfite OJ9787WBLU

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

261

Informations de copyright

© 2024. The Author(s).

Références

Boulias K, Greer EL. Means, mechanisms and consequences of adenine methylation in DNA. Nat Rev Genet. 2022;23:411–28.
pmcid: 9354840 doi: 10.1038/s41576-022-00456-x pubmed: 35256817
Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321:209–13.
doi: 10.1038/321209a0 pubmed: 2423876
Holliday R, Pugh JE. DNA modification mechanisms and gene activity during development. Science. 1975;187:226–32.
doi: 10.1126/science.187.4173.226 pubmed: 1111098
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115.
pmcid: 4015143 doi: 10.1186/gb-2013-14-10-r115 pubmed: 24138928
Shiek SS, Mani MS, Kabekkodu SP, Dsouza HS. Health repercussions of environmental exposure to lead: methylation perspective. Toxicology. 2021;461:152927.
doi: 10.1016/j.tox.2021.152927 pubmed: 34492314
Nishiyama A, Nakanishi M. Navigating the DNA methylation landscape of cancer. Trends Genet. 2021;37:1012–27.
doi: 10.1016/j.tig.2021.05.002 pubmed: 34120771
Grunau C, Clark SJ, Rosenthal A. Bisulfite genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res. 2001;29:E65–75.
pmcid: 55789 doi: 10.1093/nar/29.13.e65 pubmed: 11433041
Vaisvila R, Ponnaluri VKC, Sun Z, Langhorst BW, Saleh L, Guan S, et al. Enzymatic methyl sequencing detects DNA methylation at single-base resolution from picograms of DNA. Genome Res. 2021. https://doi.org/10.1101/gr.266551.120 .
doi: 10.1101/gr.266551.120 pmcid: 8256858 pubmed: 34140313
Pääbo S. Ancient DNA: extraction, characterization, molecular cloning, and enzymatic amplification. Proc Natl Acad Sci U S A. 1989;86:1939–43.
pmcid: 286820 doi: 10.1073/pnas.86.6.1939 pubmed: 2928314
Noonan JP, Hofreiter M, Smith D, Priest JR, Rohland N, Rabeder G, et al. Genomic sequencing of Pleistocene cave bears. Science. 2005;309:597–9.
doi: 10.1126/science.1113485 pubmed: 15933159
Llamas B, Holland ML, Chen K, Cropley JE, Cooper A, Suter CM. High-resolution analysis of cytosine methylation in ancient DNA. PLoS ONE. 2012;7:e30226.
pmcid: 3261890 doi: 10.1371/journal.pone.0030226 pubmed: 22276161
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.
pmcid: 4445908 doi: 10.1371/journal.pone.0125344 pubmed: 26016479
Schmidt M, Maixner F, Hotz G, Pap I, Szikossy I, Pálfi G, et al. DNA methylation profiling in mummified human remains from the eighteenth-century. Sci Rep. 2021;11:15493.
pmcid: 8322318 doi: 10.1038/s41598-021-95021-7 pubmed: 34326450
Briggs AW, Stenzel U, Johnson PLF, Green RE, Kelso J, Prüfer K, et al. Patterns of damage in genomic DNA sequences from a Neandertal. Proc Natl Acad Sci U S A. 2007;104:14616–21.
pmcid: 1976210 doi: 10.1073/pnas.0704665104 pubmed: 17715061
Sawyer S, Krause J, Guschanski K, Savolainen V, Pääbo S. Temporal patterns of nucleotide misincorporations and DNA fragmentation in ancient DNA. PLoS ONE. 2012;7:e34131.
pmcid: 3316601 doi: 10.1371/journal.pone.0034131 pubmed: 22479540
Briggs AW, Stenzel U, Meyer M, Krause J, Kircher M, Pääbo S. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res. 2010;38:e87.
doi: 10.1093/nar/gkp1163 pubmed: 20028723
Gokhman D, Lavi E, Prüfer K, Fraga MF, Riancho JA, Kelso J, et al. Reconstructing the DNA methylation maps of the Neandertal and the Denisovan. Science. 2014;344:523–7.
doi: 10.1126/science.1250368 pubmed: 24786081
Hanghøj K, Renaud G, Albrechtsen A, Orlando L. DamMet: ancient methylome mapping accounting for errors, true variants, and post-mortem DNA damage. Gigascience. 2019;8. Available from: https://doi.org/10.1093/gigascience/giz025 .
Gokhman D, Mishol N, de Manuel M, de Juan D, Shuqrun J, Meshorer E, et al. Reconstructing Denisovan anatomy using DNA methylation maps. Cell. 2020;180:601.
doi: 10.1016/j.cell.2020.01.020 pubmed: 32032517
Gokhman D, Nissim-Rafinia M, Agranat-Tamir L, Housman G, García-Pérez R, Lizano E, et al. Differential DNA methylation of vocal and facial anatomy genes in modern humans. Nat Commun. 2020;11:1189.
pmcid: 7055320 doi: 10.1038/s41467-020-15020-6 pubmed: 32132541
Gokhman D, Malul A, Carmel L. Inferring past environments from ancient epigenomes. Mol Biol Evol. 2017;34:2429–38.
pmcid: 5850778 doi: 10.1093/molbev/msx211 pubmed: 28957511
Liu X, Seguin-Orlando A, Chauvey L, Tressières G, Schiavinato S, Tonasso-Calvière L, et al. DNA methylation-based profiling of horse archaeological remains for age-at-death and castration. iScience. 2023;26:106144.
pmcid: 9950528 doi: 10.1016/j.isci.2023.106144 pubmed: 36843848
Niiranen L, Leciej D, Edlund H, Bernhardsson C, Fraser M, Quinto FS, et al. Epigenomic modifications in modern and ancient genomes. Genes. 2022;13. Available from: https://doi.org/10.3390/genes13020178 .
Barouch A, Mathov Y, Meshorer E, Yakir B, Carmel L. Reconstructing DNA methylation maps of ancient populations. Nucleic Acids Res. 2024;52(4):1602–12.
Website. Available from: David Reich, Swapan Mallick. 2024. “Allen Ancient Genome Diversity Project/John Templeton Ancient DNA Atlas.” Https://reich.hms.harvard.edu/ancient-Genome-Diversity-Project .
Mathieson I, Alpaslan-Roodenberg S, Posth C, Szécsényi-Nagy A, Rohland N, Mallick S, et al. The genomic history of southeastern Europe. Nature. 2018;555:197–203.
pmcid: 6091220 doi: 10.1038/nature25778 pubmed: 29466330
Lazaretov IP, Polyakov AV. Chronology and periodization of the Southern Siberia bronze age sites. In: Shamshin AB, editor. Etnokul’turnye processy v Verhnem Priob’e I sopredelnykh regionakh v konce epokhi bronzy. Barnaul: Koncept; 2008. p. 33–55.
Ráduly E. A váci Fehérek templom kriptafeltárása. Műtárgyvédelem. 1997;26:21–7.
Zomborka M. Excavation of the crypt of the Dominican Church. Vác Magyar Múzeumok. 1996;2:3–7.
Fletcher HA, Donoghue HD, Holton J, Pap I, Spigelman M. Widespread occurrence of Mycobacterium tuberculosis DNA from 18th-19th century Hungarians. Am J Phys Anthropol. 2003;120:144–52.
doi: 10.1002/ajpa.10114 pubmed: 12541332
Kay GL, Sergeant MJ, Zhou Z, Chan JZ-M, Millard A, Quick J, et al. Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe. Nat Commun. 2015;6:6717.
doi: 10.1038/ncomms7717 pubmed: 25848958
Pap I, Józsa L, Repa I, Bajzik G, Lakhani SR, Donoghue HD, Spigelman M. 18–19th century tuberculosis in naturally mummified individuals (Vác, Hungary). In: Pálfi Gy, Dutour O, Deák J, Hutás I, editors. Tuberculosis: past and present. Budapest:Golden Book Publisher; 1999. p. 421–8.
Pap I, Susa É, Józsa L. Mummies from the 18-19th century Dominican Church of Vác, Hungary. Acta Biol Hung. 1997;42:107–12.
Pap I, Szikossy I, Kustár Á, Bajzáth J. Behind the curtain: secrets, fates, MUMMIES – temporary exhibition of the Hungarian Natural History Museum, Budapest. In: Wieczorek A, Rosendahl W, Wiegand H, editors. Mumien und Museen Kolloquium zur Ausstellung MUMIEN Der Traum vom ewigen Leben REMmagazin Sonderveröffentlichung 2, Proceedings of the Symposium Mumien und Museen. Mannheim:Reiss-Engelhorn-Museum; 2009. p. 57–60.
Ildikó S. Sebészeti beavatkozások nyomai a XVIII. századi váci múmiákon [phd]. szte; 2020. Available from: http://doktori.bibl.u-szeged.hu/10693/ . Cited 2023 Oct 27.
Szikossy I, Kustár Á, Guba ZS, Kristóf LA, Pap I. Mummies from Hungary. Naturally mummified corpses from the Dominican Church in Vác, Hungary. In: Wieczorek A, Rosendahl W, editors. Mummies of the World American Exhibitions Inc, Reiss-Engelhorn-Museum, Mannheim. Munich:Prestel Verlag; 2010. p.160–171.
Szikossy I, Kristóf LA, Pap I. Mummies found in the Dominican Church of Vác, Hungary. In: Wieczorek A, Rosendahl W, editors. Mummies of the World American Exhibitions Inc, Reiss-Engelhorn-Museum, Mannheim. Munich:Prestel Verlag; 2010. p. 355–356.
Donoghue HD, Pap I, Szikossy I, Spigelman M. Detection and characterization of Mycobacterium tuberculosis DNA in 18th century Hungarians with pulmonary and extra-pulmonary tuberculosis. In: Gill-Frerking H, Rosendahl W, Zink A, Piombino-Mascasli D, editors. Yearbook of mummy studies. Munich:Verlag Dr. Friedrich Pfeil; 2011. p. 51–56.
Donoghue HD, Pap I, Szikossy I, Spigelman M. The Vác Mummy Project: investigation of 265 eighteenth-century mummified remains from the TB pandemic era. In: Shin DH, Bianucci R, editors. The Handbook of Mummy Studies: New Frontiers in Scientific and Cultural Perspectives. Singapore: Springer Singapore; 2021. p. 777–805.
doi: 10.1007/978-981-15-3354-9_21
Antonio ML, Weiß CL, Gao Z, Sawyer S, Oberreiter V, Moots HM, et al. Stable population structure in Europe since the Iron Age, despite high mobility. bioRxiv. 2022. Available from: https://doi.org/10.1101/2022.05.15.491973 .
Meyer M, Kircher M. Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb Protoc. 2010;2010:db.prot5448.
doi: 10.1101/pdb.prot5448
Kapp JD, Green RE, Shapiro B. A fast and efficient single-stranded genomic library preparation method optimized for ancient DNA. J Hered. 2021;112:241–9.
pmcid: 8141684 doi: 10.1093/jhered/esab012 pubmed: 33768239
Gansauge M-T, Gerber T, Glocke I, Korlevic P, Lippik L, Nagel S, et al. Single-stranded DNA library preparation from highly degraded DNA using T4 DNA ligase. Nucleic Acids Res. 2017;45: e79.
pmcid: 5449542 pubmed: 28119419
Gansauge M-T, Meyer M. Single-stranded DNA library preparation for the sequencing of ancient or damaged DNA. Nat Protoc. 2013;8:737–48.
doi: 10.1038/nprot.2013.038 pubmed: 23493070
Glocke I, Meyer M. Extending the spectrum of DNA sequences retrieved from ancient bones and teeth. Genome Res. 2017;27:1230–7.
pmcid: 5495074 doi: 10.1101/gr.219675.116 pubmed: 28408382
Bokelmann L, Glocke I, Meyer M. Reconstructing double-stranded DNA fragments on a single-molecule level reveals patterns of degradation in ancient samples. Genome Res. 2020;30:1449–57.
pmcid: 7605269 doi: 10.1101/gr.263863.120 pubmed: 32963029
Kircher M, Sawyer S, Meyer M. Double indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform. Nucleic Acids Res. 2012;40:e3.
doi: 10.1093/nar/gkr771 pubmed: 22021376
Meyer M, Kircher M, Gansauge M-T, Li H, Racimo F, Mallick S, et al. A high-coverage genome sequence from an archaic Denisovan individual. Science. 2012;338:222–6.
pmcid: 3617501 doi: 10.1126/science.1224344 pubmed: 22936568
Lee J-H, Park S-J, Nakai K. Differential landscape of non-CpG methylation in embryonic stem cells and neurons caused by DNMT3s. Sci Rep. 2017;7:11295.
pmcid: 5595995 doi: 10.1038/s41598-017-11800-1 pubmed: 28900200
Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LT-Y, Kohlbacher O, et al. Charting a dynamic DNA methylation landscape of the human genome. Nature. 2013;500:477–81.
pmcid: 3821869 doi: 10.1038/nature12433 pubmed: 23925113
Loyfer N, Magenheim J, Peretz A, Cann G, Bredno J, Klochendler A, et al. A DNA methylation atlas of normal human cell types. Nature. 2023;613:355–64.
pmcid: 9811898 doi: 10.1038/s41586-022-05580-6 pubmed: 36599988
Rohland N, Harney E, Mallick S, Nordenfelt S, Reich D. Partial uracil–DNA–glycosylase treatment for screening of ancient DNA. Philos Trans R Soc Lond B Biol Sci. 2015;370:20130624.
pmcid: 4275898 doi: 10.1098/rstb.2013.0624 pubmed: 25487342
Ziller MJ, Hansen KD, Meissner A, Aryee MJ. Coverage recommendations for methylation analysis by whole-genome bisulfite sequencing. Nat Methods. 2015;12:230–2 1 p following 232.
doi: 10.1038/nmeth.3152 pubmed: 25362363
Olova N, Krueger F, Andrews S, Oxley D, Berrens RV, Branco MR, et al. Comparison of whole-genome bisulfite sequencing library preparation strategies identifies sources of biases affecting DNA methylation data. Genome Biol. 2018;19:33.
pmcid: 5856372 doi: 10.1186/s13059-018-1408-2 pubmed: 29544553
Feng S, Zhong Z, Wang M, Jacobsen SE. Efficient and accurate determination of genome-wide DNA methylation patterns in Arabidopsis thaliana with enzymatic methyl sequencing. Epigenetics Chromatin. 2020;13:42.
pmcid: 7542392 doi: 10.1186/s13072-020-00361-9 pubmed: 33028374
Morrison J, Koeman JM, Johnson BK, Foy KK, Beddows I, Zhou W, et al. Evaluation of whole-genome DNA methylation sequencing library preparation protocols. Epigenetics Chromatin. 2021;14:28.
pmcid: 8214260 doi: 10.1186/s13072-021-00401-y pubmed: 34147133
Pinhasi R, Fernandes DM, Sirak K, Cheronet O. Isolating the human cochlea to generate bone powder for ancient DNA analysis. Nat Protoc. 2019;14:1194–205.
doi: 10.1038/s41596-019-0137-7 pubmed: 30842617
Dabney J, Knapp M, Glocke I, Gansauge M-T, Weihmann A, Nickel B, 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.
pmcid: 3785785 doi: 10.1073/pnas.1314445110 pubmed: 24019490
Rohland N, Mallick S, Mah M, Maier R, Patterson N, Reich D. Three assays for in-solution enrichment of ancient human DNA at more than a million SNPs. Genome Res. 2022;32:2068–78.
pmcid: 9808625 doi: 10.1101/gr.276728.122 pubmed: 36517229
Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal. 2011;17:10–2.
doi: 10.14806/ej.17.1.200
Krueger F, Andrews SR. Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics. 2011;27:1571–2.
pmcid: 3102221 doi: 10.1093/bioinformatics/btr167 pubmed: 21493656
Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V, Pollard MO, et al. Twelve years of SAMtools and BCFtools. Gigascience. 2021;10. https://doi.org/10.1093/gigascience/giab008 .
Website. Available from: R. Core Team. An introduction to R. 2015. https://www.R-project.org .
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60.
pmcid: 2705234 doi: 10.1093/bioinformatics/btp324 pubmed: 19451168
Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26:841–2.
pmcid: 2832824 doi: 10.1093/bioinformatics/btq033 pubmed: 20110278
Akalin A, Kormaksson M, Li S, Garrett-Bakelman FE, Figueroa ME, Melnick A, et al. methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 2012;13:R87.
pmcid: 3491415 doi: 10.1186/gb-2012-13-10-r87 pubmed: 23034086
Sawyer S, Gelabert P, Yakir B, Lizcano AL, Sperduti A, Bondioli, et al. Improved detection of methylation in ancient DNA. Dataset. European nucleotide archive. https://www.ebi.ac.uk/ena/browser/view/PRJEB71420 .

Auteurs

Susanna Sawyer (S)

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria. susanna.sawyer@univie.ac.at.
Human Evolution and Archaeological Sciences, University of Vienna, Vienna, Austria. susanna.sawyer@univie.ac.at.
ORCID: 0000-0002-8477-6089

Pere Gelabert (P)

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.
Human Evolution and Archaeological Sciences, University of Vienna, Vienna, Austria.

Benjamin Yakir (B)

Department of Statistics, The Faculty of Social Science, The Hebrew University Mount Scopus, Jerusalem, Israel.

Alejandro Llanos-Lizcano (A)

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.
Facultad de Química y Farmacia, Universidad del Atlántico, Barranquilla, Colombia.

Alessandra Sperduti (A)

Museo Delle Civiltà, Servizio Di Bioarcheologia, Rome, Italy.
Dipartimento di Asia, Africa e Mediterraneo, Università degli Studi di Napoli "L'Orientale", Naples, Italy.

Luca Bondioli (L)

Università Di Padova, Dipartimento Dei Beni Culturali, Padua, Italy.

Olivia Cheronet (O)

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.
Human Evolution and Archaeological Sciences, University of Vienna, Vienna, Austria.

Christine Neugebauer-Maresch (C)

Austrian Archaeological Institute, Austrian Academy of Sciences, Vienna, Austria.
Institute of Prehistory and Early History, University of Vienna, Vienna, Austria.

Maria Teschler-Nicola (M)

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.
Department of Anthropology, Natural History Museum Vienna, Vienna, Austria.

Mario Novak (M)

Centre for Applied Bioanthropology, Institute for Anthropological Research, Zagreb, Croatia.
Department of Archaeology and Heritage, Faculty of Humanities, University of Primorska, Koper, Slovenia.

Ildikó Pap (I)

Department of Biological Anthropology, Institute of Biology, University of Szeged, Szeged, Hungary.
Department of Anthropology, Hungarian Natural History Museum, Budapest, Hungary.
Department of Biological Anthropology, Eötvös Loránd University, Budapest, Hungary.

Ildikó Szikossy (I)

, Budapest, Hungary.

Tamás Hajdu (T)

Department of Biological Anthropology, Eötvös Loránd University, Budapest, Hungary.

Vyacheslav Moiseyev (V)

Peter the Great Museum of Anthropology and Ethnography (Kunstkamera), RAS, Saint Petersburg, Russia.

Andrey Gromov (A)

Peter the Great Museum of Anthropology and Ethnography (Kunstkamera), RAS, Saint Petersburg, Russia.

Gunita Zariņa (G)

Institute of Latvian History, University of Latvia, Riga, Latvia.

Eran Meshorer (E)

The Edmond and Lily Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

Liran Carmel (L)

Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

Ron Pinhasi (R)

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria. ron.pinhasi@univie.ac.at.
Human Evolution and Archaeological Sciences, University of Vienna, Vienna, Austria. ron.pinhasi@univie.ac.at.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Improved detection of methylation in ancient DNA.
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN ancien › Improved detection of methylation in ancient DNA.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Improved detection of methylation in ancient DNA.
questionsmedicales.fr › Produits chimiques inorganiques › Sulfites › Improved detection of methylation in ancient DNA.
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Improved detection of methylation in ancient DNA.