TY - JOUR
T1 - Pros and cons of methylation-based enrichment methods for ancient DNA
AU - Seguin-Orlando, Andaine
AU - Gamba, Cristina
AU - Sarkissian, Clio Der
AU - Ermini, Luca
AU - Louvel, Guillaume
AU - Boulygina, Eugenia
AU - Sokolov, Alexey
AU - Nedoluzhko, Artem
AU - Lorenzen, Eline D.
AU - Lopez, Patricio
AU - McDonald, H. Gregory
AU - Scott, Eric
AU - Tikhonov, Alexei
AU - Stafford, Thomas W.
AU - Alfarhan, Ahmed H.
AU - Alquraishi, Saleh A.
AU - Al-Rasheid, Khaled A.S.
AU - Shapiro, Beth
AU - Willerslev, Eske
AU - Prokhortchouk, Egor
AU - Orlando, Ludovic
N1 - Funding Information:
This work was supported by the Danish Council for Independent Research, Natural Sciences (FNU); the Danish National Research Foundation (DNRF94); “Chaires d’Attractivité 2014” IDEX, University of Toulouse; a Marie-Curie Career Integration grant (FP7 CIG-293845); the International Research Group Program (IRG14-08), Deanship of Scientific Research (King Saud University, Saudi Arabia). CG and LE were supported by Marie-Curie Intra-European Fellowships (FP7-IEF-328024 and FP7 IEF-302617). BS was supported by the Gordon and Betty Moore Foundation. Equid samples were obtained from the GNL Quintero project and the Natural and Cultural History Museum of the Atacama Desert (Museo de Historia Natural y Cultural del Desierto de Atacama). We thank the Smithsonian Institution for allowing us to sample Equus lambei and use its data for this study; S. Liu for providing access to the annotations on the polar bear genome; T. Brand, P. Selmer Olsen and the staff of the Danish National High-throughput DNA Sequencing Centre for technical assistance.
PY - 2015/7/2
Y1 - 2015/7/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84934783998&partnerID=8YFLogxK
U2 - 10.1038/srep11826
DO - 10.1038/srep11826
M3 - Article
C2 - 26134828
AN - SCOPUS:84934783998
SN - 2045-2322
VL - 5
JO - Scientific Reports
JF - Scientific Reports
M1 - 11826
ER -