Temporal patterns of nucleotide misincorporations and DNA fragmentation in ancient DNA
Open accessAbstract
DNA that survives in museum specimens, bones and other tissues recovered by archaeologists is invariably fragmented and chemically modified. The extent to which such modifications accumulate over time is largely unknown but could potentially be used to differentiate between endogenous old DNA and present-day DNA contaminating specimens and experiments. Here we examine mitochondrial DNA sequences from tissue remains that vary in age between 18 and 60,000 years with respect to three molecular features: fragment length, base composition at strand breaks, and apparent C to T substitutions. We find that fragment length does not decrease consistently over time and that strand breaks occur preferentially before purine residues by what may be at least two different molecular mechanisms that are not yet understood. In contrast, the frequency of apparent C to T substitutions towards the 5'-ends of molecules tends to increase over time. These nucleotide misincorporations are thus a useful tool to distinguish recent from ancient DNA sources in specimens that have not been subjected to unusual or harsh treatments.
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Ancient DNA typically consists of short fragments in the range of 10-150 bp.
“Ancient DNA typically consists of short fragments in the range of 10–150 bp (Sawyer et al. 2012).”
From Unravelling reference bias in ancient DNA datasets (2024) · cites this paper as Sawyer et al. 2012
The Introduction identifies short fragment length as a feature of ancient DNA, and the Results report median mitochondrial-DNA fragment lengths of 44–170 bp across the sampled libraries. The paper does not establish the claimed typical range of 10–150 bp for ancient DNA generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredaDNA damage results in C-to-T and G-to-A substitutions.
“This therefore results in a pattern of C-to-T substitutions. When a double-stranded library preparation is used, these substitutions can occur on the opposite strand thus resulting in G-to-A substitutions due to base complementarity.”
From <tt>SAFARI</tt> : pangenome alignment of ancient DNA using purine/pyrimidine encodings (2025) · cites this paper as [5]
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- Authors
- Sawyer, S., Krause, J., Guschanski, K., Savolainen, V., & Pääbo, S.
- Affiliations
- Max Planck Society (DE)
- University of Tübingen (DE)
- University of Lausanne (CH)
- Imperial College London (GB)
- Corresponding author
- Sawyer, Susanna
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-03-30
- Volume
- 7
- Issue
- 3
- Pages
- e34131
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3316601
- OpenAlex
- W2022327489
- Cited by
- 489
- References
- 26
- Citations by year
- 2026: 26 · 2025: 31 · 2024: 22 · 2023: 29 · 2022: 33 · 2021: 56 · 2020: 54 · 2019: 27 · 2018: 52 · 2017: 46 · 2016: 31 · 2015: 33 · 2014: 25 · 2013: 19 · 2012: 4
- FWCI
- 15.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- Max-Planck-Gesellschaft
- Natural Environment Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Archaeology and ancient environmental studies
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Keywords
- ancient DNA, DNA fragmentation, nucleotide misincorporation, strand breaks, mitochondrial DNA, DNA damage, DNA contamination, temporal patterns, museum specimens, endogenous DNA
- MeSH terms
- Animals, Base Composition, DNA, DNA Damage, DNA, Mitochondrial, Gorilla gorilla, Humans, Paleontology, Time Factors, Gene Library, Polymerase Chain Reaction, Sequence Analysis, DNA, DNA Fragmentation
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