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 Lorenzen; Patricio Lopez; H. Gregory McDonald; Eric Scott; Alexei Tikhonov; Thomas Stafford jr.; Ahmed H. Alfarhan; Saleh A. Alquraishi; Khaled A. S. Al-Rasheid; Beth Shapiro; Eske Willerslev; Egor Prokhortchouk; Ludovic Antoine Alexandre Orlando

doi:10.1038/srep11826

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 Lorenzen, Patricio Lopez, H. Gregory McDonald, Eric Scott, Alexei Tikhonov, Thomas Stafford jr., Ahmed H. Alfarhan, Saleh A. Alquraishi, Khaled A. S. Al-Rasheid, Beth Shapiro, Eske Willerslev, Egor ProkhortchoukLudovic Antoine Alexandre Orlando^*

^*Corresponding author for this work

24 Citations (Scopus)

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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.

Original language	English
Article number	11826
Journal	Scientific Reports
Volume	5
Number of pages	15
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep11826
Publication status	Published - 2015

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Seguin_Orlando_2015_Pros_and_consFinal published version, 979 KBLicence: CC BY

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Seguin-Orlando, A., Gamba, C., Der Sarkissian, C., Ermini, L., Louvel, G., Boulygina, E., Sokolov, A., Nedoluzhko, A., Lorenzen, E., Lopez, P., McDonald, H. G., Scott, E., Tikhonov, A., Stafford jr., T., Alfarhan, A. H., Alquraishi, S. A., Al-Rasheid, K. A. S., Shapiro, B., Willerslev, E., ... Orlando, L. A. A. (2015). Pros and cons of methylation-based enrichment methods for ancient DNA. Scientific Reports, 5, [11826]. https://doi.org/10.1038/srep11826

Seguin-Orlando, A, Gamba, C, Der Sarkissian, C, Ermini, L, Louvel, G, Boulygina, E, Sokolov, A, Nedoluzhko, A, Lorenzen, E, Lopez, P, McDonald, HG, Scott, E, Tikhonov, A, Stafford jr., T, Alfarhan, AH, Alquraishi, SA, Al-Rasheid, KAS, Shapiro, B, Willerslev, E, Prokhortchouk, E & Orlando, LAA 2015, 'Pros and cons of methylation-based enrichment methods for ancient DNA', Scientific Reports, vol. 5, 11826. https://doi.org/10.1038/srep11826

@article{ee20884dc4c14c309e8b31500f99428e,

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.",

author = "Andaine Seguin-Orlando and Cristina Gamba and {Der Sarkissian}, Clio and Luca Ermini and Guillaume Louvel and Eugenia Boulygina and Alexey Sokolov and Artem Nedoluzhko and Eline Lorenzen and Patricio Lopez and McDonald, {H. Gregory} and Eric Scott and Alexei Tikhonov and {Stafford jr.}, Thomas and Alfarhan, {Ahmed H.} and Alquraishi, {Saleh A.} and Al-Rasheid, {Khaled A. S.} and Beth Shapiro and Eske Willerslev and Egor Prokhortchouk and Orlando, {Ludovic Antoine Alexandre}",

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doi = "10.1038/srep11826",

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journal = "Scientific Reports",

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T1 - Pros and cons of methylation-based enrichment methods for ancient DNA

AU - Seguin-Orlando, Andaine

AU - Gamba, Cristina

AU - Der Sarkissian, Clio

AU - Ermini, Luca

AU - Louvel, Guillaume

AU - Boulygina, Eugenia

AU - Sokolov, Alexey

AU - Nedoluzhko, Artem

AU - Lorenzen, Eline

AU - Lopez, Patricio

AU - McDonald, H. Gregory

AU - Scott, Eric

AU - Tikhonov, Alexei

AU - Stafford jr., Thomas

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 Antoine Alexandre

PY - 2015

Y1 - 2015

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.

U2 - 10.1038/srep11826

DO - 10.1038/srep11826

M3 - Journal article

C2 - 26134828

AN - SCOPUS:84934783998

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 11826

ER -

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

Abstract

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