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

Seguin-Orlando, Andaine, Gamba, Cristina, Sarkissian, Clio Der, Ermini, Luca, Louvel, Guillaume, Boulygina, Eugenia, Sokolov, Alexey, Nedoluzhko, Artem, Lorenzen, Eline D., Lopez, Patricio, McDonald, H. Gregory, Scott, Eric, Tikhonov, Alexei, Stafford,, Thomas W., Alfarhan, Ahmed H., Alquraishi, Saleh A., Al-Rasheid, Khaled A. S., Shapiro, Beth, Willerslev, Eske, Prokhortchouk, Egor, Orlando, Ludovic·2015·Scientific Reports

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.

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  • Immunoprecipitation is likewise extremely limited in practice due to the fast postmortem decay of CpG dinucleotides and DNA fragmentation, which reduce the number of potential DNA methylation targets available per fragment.

    “Immunoprecipitation is likewise extremely limited in practice due to the fast postmortem decay of CpG dinucleotides 167 and DNA fragmentation 62 , which reduce the number of potential DNA methylation targets available per fragment.”

    From Ancient DNA analysis (2021) · cites this paper as [62]

    The Results (Size and base compositional bias; page unavailable) find that shorter ancient DNA fragments have fewer CpG targets and that fragmentation limits MBD enrichment efficiency. The paper studies MBD-based enrichment, not immunoprecipitation specifically, so it does not establish that limitation for the method named in the claim. (LLM, conf=0.86)

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Metadata

Authors
Seguin-Orlando, A., Gamba, C., Sarkissian, C. D., Ermini, L., Louvel, G., Boulygina, E., Sokolov, A., Nedoluzhko, A., Lorenzen, E. D., Lopez, P., McDonald, H. G., Scott, E., Tikhonov, A., Stafford, Alfarhan, A. H., Alquraishi, S. A., Al-Rasheid, K. A. S., Shapiro, B., Willerslev, E., Prokhortchouk, E., & Orlando, L.
Venue
Scientific Reports
Published
2015-07-02
Volume
5
Issue
1
ISSN
2045-2322
Cited by
58
References
14
Language
en

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