title: Pros and cons of methylation-based enrichment methods for ancient DNA.
abstract: The recent discovery that DNA methylation survives in fossil material provides an opportunity for novel molecular approaches in palaeogenomics. Here, we apply to ancient DNA extracts the probe-independent Methylated Binding Domains (MBD)-based enrichment method, which targets DNA molecules containing methylated CpGs. Using remains of a Palaeo-Eskimo Saqqaq individual, woolly mammoths, polar bears and two equine species, we confirm that DNA methylation survives in a variety of tissues, environmental contexts and over a large temporal range (4,000 to over 45,000 years before present). MBD enrichment, however, appears principally biased towards the recovery of CpG-rich and long DNA templates and is limited by the fast post-mortem cytosine deamination rates of methylated epialleles. This method, thus, appears only appropriate for the analysis of ancient methylomes from very well preserved samples, where both DNA fragmentation and deamination have been limited. This work represents an essential step toward the characterization of ancient methylation signatures, which will help understanding the role of epigenetic changes in past environmental and cultural transitions.
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.|National High-throughput DNA Sequencing Centre, Øster Farimagsgade 2D, 1353K Copenhagen, Denmark.
authors.forename: Andaine
authors.initials: A
authors.lastname: Seguin-Orlando
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gamba
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.
authors.forename: Clio Der
authors.initials: C
authors.lastname: Sarkissian
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.
authors.forename: Luca
authors.initials: L
authors.lastname: Ermini
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Louvel
authors.affiliation: National Research Centre Kurchatov Institute, 1, Akademika Kurchatova, Moscow, 123182, Russian Federation.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Boulygina
authors.affiliation: Centre Bioengineering, Russian Academy of Sciences, Prospekt 60-Letiya Oktyabrya 7/1, Moscow, 117312, Russian Federation.
authors.forename: Alexey
authors.initials: A
authors.lastname: Sokolov
authors.affiliation: National Research Centre Kurchatov Institute, 1, Akademika Kurchatova, Moscow, 123182, Russian Federation.
authors.forename: Artem
authors.initials: A
authors.lastname: Nedoluzhko
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.|Department of Integrative Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Eline D
authors.initials: ED
authors.lastname: Lorenzen
authors.affiliation: Department of Anthropology, Universidad de Chile, Ignacio Carrera Pinto 1045, Ñuñoa, Santiago, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Park Museum Management Program, National Park Service, 1201 Oakridge Drive, Suite 150, Fort Collins, Colorado 80525, USA.
authors.forename: H Gregory
authors.initials: HG
authors.lastname: McDonald
authors.affiliation: San Bernardino County Museum, Division of Geological Sciences, 2024 Orange Tree Lane, Redlands, California 92374, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Scott
authors.affiliation: Zoological Institute of Russian Academy of Sciences, 199034 St. Petersburg, Russian Federation.|Institute of Applied Ecology of the North, North-Eastern Federal University, 677980 Yakutsk, Russian Federation.
authors.forename: Alexei
authors.initials: A
authors.lastname: Tikhonov
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Stafford
authors.affiliation: Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Alfarhan
authors.affiliation: Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Alquraishi
authors.affiliation: Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Khaled A S
authors.initials: KAS
authors.lastname: Al-Rasheid
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California Santa Cruz, Santa Cruz, CA 95060, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Shapiro
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.
authors.forename: Eske
authors.initials: E
authors.lastname: Willerslev
authors.affiliation: National Research Centre Kurchatov Institute, 1, Akademika Kurchatova, Moscow, 123182, Russian Federation.
authors.forename: Egor
authors.initials: E
authors.lastname: Prokhortchouk
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.|Université de Toulouse, University Paul Sabatier (UPS), Laboratoire AMIS, CNRS UMR 5288, 37 allées Jules Guesde, 31000 Toulouse, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Orlando
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D019175:DNA Methylation / Q000235:genetics*; D005580:Fossils; D056665:Mammoths / Q000235:genetics*; D001503:Ursidae / Q000235:genetics*
chemical_list: D004247:DNA