The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967
Metagenomic microbial community profiling using unique clade-specific marker genes
Segata, N., Waldron, L., Ballarini, A., Narasimhan, V., Jousson, O., & Huttenhower, C. (2012) · Nature Methods · doi:10.1038/nmeth.2066 · Cited by 1,776
mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters
Jónsson, H., Ginolhac, A., Schubert, M., Johnson, P. L. F., & Orlando, L. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt193 · Cited by 1,669
Self-citationCharting a dynamic DNA methylation landscape of the human genome
Ziller, M. J., Gu, H., Müller, F., Donaghey, J., Tsai, L. T.-Y., Kohlbacher, O., De Jager, P. L., Rosen, E. D., Bennett, D. A., Bernstein, B. E., et al. (2013) · Nature · doi:10.1038/nature12433 · Cited by 1,357
Ancient human genome sequence of an extinct Palaeo-Eskimo
Rasmussen, M., Li, Y., Lindgreen, S., Pedersen, J. S., Albrechtsen, A., Moltke, I., Metspalu, M., Metspalu, E., Kivisild, T., Gupta, R., et al. (2010) · Nature · doi:10.1038/nature08835 · Cited by 849
Self-citationGenome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
Wade, C. M., Giulotto, E., Sigurdsson, S., Zoli, M., Gnerre, S., Imsland, F., Lear, T. L., Adelson, D. L., Bailey, E., Bellone, R. R., et al. (2009) · Science · doi:10.1126/science.1178158 · Cited by 822
DNA analysis of an early modern human from Tianyuan Cave, China
Fu, Q., Meyer, M., Gao, X., Stenzel, U., Burbano, H. A., Kelso, J., & Pääbo, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221359110 · Cited by 608
Partial uracil–DNA–glycosylase treatment for screening of ancient DNA
Rohland, N., Harney, E., Mallick, S., Nordenfelt, S., & Reich, D. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2013.0624 · Cited by 572
A mitochondrial genome sequence of a hominin from Sima de los Huesos
Meyer, M., Fu, Q., Aximu-Petri, A., Glocke, I., Nickel, B., Arsuaga, J.-L., Martínez, I., Gracia, A., de Castro, J. M. B., Carbonell, E., et al. (2014) · Nature · doi:10.1038/nature12788 · Cited by 534
Temporal patterns of nucleotide misincorporations and DNA fragmentation in ancient DNA
Sawyer, S., Krause, J., Guschanski, K., Savolainen, V., & Pääbo, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034131 · Cited by 489
Improving ancient DNA read mapping against modern reference genomes
Schubert, M., Ginolhac, A., Lindgreen, S., Thompson, J. F., AL-Rasheid, K. A., Willerslev, E., Krogh, A., & Orlando, L. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-178 · Cited by 325
Self-citationA Method for Selectively Enriching Microbial DNA from Contaminating Vertebrate Host DNA
Feehery, G. R., Yigit, E., Oyola, S. O., Langhorst, B. W., Schmidt, V. T., Stewart, F. J., Dimalanta, E. T., Amaral-Zettler, L. A., Davis, T., Quail, M. A., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076096 · Cited by 212
Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear
Lindqvist, C., Schuster, S. C., Sun, Y., Talbot, S. L., Qi, J., Ratan, A., Tomsho, L. P., Kasson, L., Zeyl, E., Aars, J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914266107 · Cited by 193
Complete Mitochondrial Genome and Phylogeny of Pleistocene MammothMammuthus primigenius
Rogaev, E. I., Moliaka, Y. K., Malyarchuk, B. A., Kondrashov, F. A., Derenko, M. V., Chumakov, I., & Grigorenko, A. P. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040073 · Cited by 137
Flagged first, then by citations
Research works printed but not linked: 48
- Orlando, L. & Cooper, A. Using Ancient DNA to Understand Evolutionary and Ecological Processes. Annu. Rev. Ecol. Evol. Syst. 45, 573–598 (2014). · DOI
- Ermini, L., Der Sarkissian, C., Willerslev, E. & Orlando, L. Major transitions in human evolution revisited: A tribute to ancient DNA. J. Hum. Evol. 79, 4–20 (2014). · DOI
- Der Sarkissian, C. et al. Ancient genomics. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370, 20130387 (2015). · DOI
- Shapiro, B. & Hofreiter, M. A Paleogenomic Perspective on Evolution and Gene Function: New Insights from Ancient DNA. Science 343, 1236573 (2014). · DOI · Paper page
- Der Sarkissian, C. et al. Shotgun microbial profiling of fossil remains. Mol. Ecol. 23, 1780–1798 (2014). · DOI
- Schubert, M. et al. Prehistoric genomes reveal the genetic foundation and cost of horse domestication. Proc. Natl. Acad. Sci. USA 111, E5661–9 (2014). · DOI · Paper page
- Ávila-Arcos, M. C. et al. Application and comparison of large-scale solution-based DNA capture-enrichment methods on ancient DNA. Sci. Rep. 1, 74 (2011). · DOI
- Gansauge, M.-T. & Meyer, M. Selective enrichment of damaged DNA molecules for ancient genome sequencing. Genome Res. 24, 1543–1549 (2014). · DOI · Paper page
- Fabre, P.-H. et al. Rodents of the Caribbean: origin and diversification of hutias unravelled by next-generation museomics. Biol. Lett. 10, 20140266 (2014). · DOI
- Schuenemann, V. J. et al. Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. Proc. Natl. Acad. Sci. USA 108, E746–752 (2011). · DOI
- Carpenter, M. L. et al. Pulling out the 1%: whole-genome capture for the targeted enrichment of ancient DNA sequencing libraries. Am. J. Hum. Genet. 93, 852–864 (2013). · DOI
- Enk, J. M. et al. Ancient whole genome enrichment using baits built from modern DNA. Mol. Biol. Evol. 31, 1292–1294 (2014). · DOI
- Briggs, A. W. et al. Targeted Retrieval and Analysis of Five Neandertal mtDNA Genomes. Science 325, 318–321 (2009). · DOI
- Mason, V. C., Li, G., Helgen, K. M. & Murphy, W. J. Efficient cross-species capture hybridization and next-generation sequencing of mitochondrial genomes from noninvasively sampled museum specimens. Genome Res. 21, 1695–1704 (2011). · DOI
- Murray, I. A. et al. The methylomes of six bacteria. Nucleic Acids Res. 40, 11450–11462 (2012). · DOI
- Smith, O. et al. Genomic methylation patterns in archaeological barley show de-methylation as a time-dependent diagenetic process. Sci. Rep. 4, 5559 (2014). · DOI · Paper page
- Rebelo, A. P., Williams, S. L. & Moraes, C. T. In vivo methylation of mtDNA reveals the dynamics of protein-mtDNA interactions. Nucleic Acids Res. 37, 6701–6715 (2009). · DOI
- Deaton, A. M. & Bird, A. CpG islands and the regulation of transcription. Genes Dev. 25, 1010–1022 (2011). · DOI · Paper page
- Pedersen, J. S. et al. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome. Genome Res. 24, 454–466 (2014). · DOI · Paper page
- Frederico, L. A., Kunkel, T. A. & Shaw, B. R. A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy. Biochemistry 29, 2532–2537 (1990). · DOI
- Shen, J. C., Rideout, W. M., 3rd & Jones, P. A. The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA. Nucleic Acids Res. 22, 972–976 (1994). · DOI
- Segata, N. et al. Metagenomic biomarker discovery and explanation. Genome Biol. 12, R60 (2011). · DOI · Paper page
- Llamas, B. et al. High-resolution analysis of cytosine methylation in ancient DNA. PLoS One 7, e30226 (2012). · DOI · Paper page
- Gokhman, D. et al. Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan. Science 344, 523–527 (2014). · DOI · Paper page
- Orlando, L. & Willerslev, E. Evolution. An epigenetic window into the past? Science 345, 511–512 (2014). · DOI
- Schwarz, C. et al. New insights from old bones: DNA preservation and degradation in permafrost preserved mammoth remains. Nucleic Acids Res. 37, 3215–3229 (2009). · DOI
- Sved, J. & Bird, A. The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model. Proc. Natl. Acad. Sci. USA 87, 4692–4696 (1990). · DOI
- Dabney, J. & Meyer, M. Length and GC-biases during sequencing library amplification: a comparison of various polymerase-buffer systems with ancient and modern DNA sequencing libraries. Biotechniques 52, 87–94 (2012). · DOI · Paper page
- Rauch, T. & Pfeifer, G. P. Methylated-CpG island recovery assay: a new technique for the rapid detection of methylated-CpG islands in cancer. Lab. Invest. 85, 1172–1180 (2005). · DOI
- Smith, C. I., Chamberlain, A. T., Riley, M. S., Stringer, C. & Collins, M. J. The thermal history of human fossils and the likelihood of successful DNA amplification. J. Hum. Evol. 45, 203–217 (2003). · DOI
- Forbes, S. L. Decomposition chemistry in a burial environment. Soil Analysis in Forensic Taphonomy. New York: CRC Press, Taylor & Francis 203–223 (2008). · DOI
- Orlando, L. et al. Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse. Nature 499, 74–78 (2013). · DOI · Paper page
- Schuenemann, V. J. et al. Genome-wide comparison of medieval and modern Mycobacterium leprae. Science 341, 179–183 (2013). · DOI · Paper page
- Yang, D. Y., Eng, B., Waye, J. S., Dudar, J. C. & Saunders, S. R. Technical note: improved DNA extraction from ancient bones using silica-based spin columns. Am. J. Phys. Anthropol. 105, 539–543 (1998). · DOI
- Fisher, D. C. et al. X-ray computed tomography of two mammoth calf mummies. J. Paleontol. 88, 664–675 (2014). · DOI
- Mashchenko, E. et al. The partial carcass of the mammoth “Zhenya” (Mammuthus primigenius) from western Taymyr Peninsula, Russia: preliminary analysis and results. in VIth International Conference on Mammoths and their Relatives, Grevena - Siatista (ed. Scientific Annals, School of Geology, Aristotle University of Thessaloniki, Greece) 102, 121–122 (2014).
- Meyer, M. & Kircher, M. Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb. Protoc. 2010, db.prot5448 (2010). · DOI
- Seguin-Orlando, A. et al. Ligation Bias in Illumina Next-Generation DNA Libraries: Implications for Sequencing Ancient Genomes. PLoS One 8, e78575 (2013). · DOI · Paper page
- Schubert, M. et al. Characterization of ancient and modern genomes by SNP detection and phylogenomic and metagenomic analysis using PALEOMIX. Nat. Protoc. 9, 1056–1082 (2014). · DOI · Paper page
- Xu, X. & Arnason, U. The complete mitochondrial DNA sequence of the horse, Equus caballus: extensive heteroplasmy of the control region. Gene 148, 357–362 (1994). · DOI
- Andrews, R. M. et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat. Genet. 23, 147 (1999). · DOI · Paper page
- Anderson, S. et al. Sequence and organization of the human mitochondrial genome. Nature 290, 457–465 (1981). · DOI
- Miller, W. et al. Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change. Proc. Natl. Acad. Sci. USA 109, E2382–90 (2012). · DOI · Paper page
- Li, H. et al. The Sequence Alignment/Map (SAM) Format and SAMtools. Bioinformatics btp352 25, 2078–2079 (2009). · DOI · Paper page
- Liu, S. et al. Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears. Cell 157, 785–794 (2014). · DOI · Paper page
- Suzuki, R. & Shimodaira, H. Pvclust: an R package for assessing the uncertainty in hierarchical clustering. Bioinformatics 22, 1540–1542 (2006). · DOI
- Fierer, N. et al. Cross-biome metagenomic analyses of soil microbial communities and their functional attributes. Proc. Natl. Acad. Sci. USA 109, 21390–21395 (2012). · DOI
- The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012). · DOI · Paper page
Cited by
Sorted by citations
Orlando, L., Allaby, R., Skoglund, P., Der Sarkissian, C., Stockhammer, P. W., Ávila-Arcos, M. C., Fu, Q., Krause, J., Willerslev, E., Stone, A. C., et al. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-020-00011-0 · Cited by 411
Self-citationHuman evolution: a tale from ancient genomes
Llamas, B., Willerslev, E., & Orlando, L. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0484 · Cited by 100
Self-citationAssessing DNA sequence alignment methods for characterizing ancient genomes and methylomes
Poullet, M., & Orlando, L. (2020) · Frontiers in Ecology and Evolution · doi:10.3389/fevo.2020.00105 · Cited by 61
Self-citation
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
- PMC
- PMC4488743
- Cited by
- 58
- References
- 14
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review