Pros and cons of methylation-based enrichment methods for ancient DNA

Andaine Seguin-Orlando, Cristina Gamba, Clio Der Sarkissian, Luca Ermini, Guillaume Louvel, Eugenia Boulygina, Alexey Sokolov, Artem Nedoluzhko, Eline D. Lorenzen, Patricio Lopez, H. Gregory McDonald, Eric Scott, Alexei Tikhonov, Thomas W. Stafford, Ahmed H. Alfarhan, Saleh A. Alquraishi, Khaled A.S. Al-Rasheid, Beth Shapiro, Eske Willerslev, Egor ProkhortchoukLudovic Orlando*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)


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.

Original languageEnglish
Article number11826
JournalScientific Reports
Publication statusPublished - 2 Jul 2015
Externally publishedYes


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