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Separating endogenous ancient DNA from modern day contamination in a Siberian Neandertal
Open accessAbstract
One of the main impediments for obtaining DNA sequences from ancient human skeletons is the presence of contaminating modern human DNA molecules in many fossil samples and laboratory reagents. However, DNA fragments isolated from ancient specimens show a characteristic DNA damage pattern caused by miscoding lesions that differs from present day DNA sequences. Here, we develop a framework for evaluating the likelihood of a sequence originating from a model with postmortem degradation-summarized in a postmortem degradation score-which allows the identification of DNA fragments that are unlikely to originate from present day sources. We apply this approach to a contaminated Neandertal specimen from Okladnikov Cave in Siberia to isolate its endogenous DNA from modern human contaminants and show that the reconstructed mitochondrial genome sequence is more closely related to the variation of Western Neandertals than what was discernible from previous analyses. Our method opens up the potential for genomic analysis of contaminated fossil material.
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“By characterizing damage patterns, users can distinguish authentic aDNA from modern contaminants, thereby ensuring the integrity of the dataset (Jónsson et al. 2013, Skoglund et al. 2014).”
From Unravelling reference bias in ancient DNA datasets (2024) · cites this paper as Skoglund et al. 2014
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“Cytosine deamination can also be estimated using the tool PMDtools 55 on data generated following full USER-treatment by conditioning on CpG dinucleotides 125 , since these are heavily methylated in the nuclear genomes of vertebrates and protected from USER degradation.”
From Ancient DNA analysis (2021) · cites this paper as [55]
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“For highly degraded or contaminated material, analyses may be conditioned on reads showing evidence of post-mortem DNA damage 55,189,192 and/or limited to transversions 7 so as to mitigate both rampant contamination and damage-related nucleotide misincorporation.”
From Ancient DNA analysis (2021) · cites this paper as [55]
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“The list of factors to consider extends far beyond the minimal data requirement for specific analyses 330 and includes: platform-specific sequence error profiles 169 ; the magnitude of post-mortem DNA damage and contamination and their impact on downstream inference 55 ; base quality rescaling 57 ; read alignment parameters 180,182 ; database selection and taxonomic classifier parameters 27,238 ;”
From Ancient DNA analysis (2021) · cites this paper as [55]
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“By characterizing damage patterns, users can distinguish authentic aDNA from modern contaminants, thereby ensuring the integrity of the dataset (J � onsson et al. 2013, Skoglund et al. 2014).”
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Metadata
- Authors
- Skoglund, P., Northoff, B. H., Shunkov, M. V., Derevianko, A. P., Pääbo, S., Krause, J., & Jakobsson, M.
- Affiliations
- Uppsala University (SE)
- Max Planck Institute for Evolutionary Anthropology (DE)
- Russian Academy of Sciences (RU)
- Palaeolithic Department, Institute of Archaeology and Ethnography, Russian Academy of Sciences Siberian Branch, Novosibirsk 630090, Russia; and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-01-27
- Volume
- 111
- Issue
- 6
- Pages
- 2229-2234
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3926038
- OpenAlex
- W2112954194
- Cited by
- 499
- References
- 58
- Citations by year
- 2026: 45 · 2025: 68 · 2024: 50 · 2023: 44 · 2022: 35 · 2021: 52 · 2020: 49 · 2019: 27 · 2018: 36 · 2017: 29 · 2016: 24 · 2015: 22 · 2014: 18
- FWCI
- 20.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- ancient DNA, Neanderthals, contamination control, mitochondrial genome, Siberia
- MeSH terms
- Animals, DNA, Mitochondrial, Humans, Molecular Sequence Data, Siberia, Neanderthals
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