The neandertal genome and ancient DNA authenticity
Open accessAbstract
Recent advances in high-thoughput DNA sequencing have made genome-scale analyses of genomes of extinct organisms possible. With these new opportunities come new difficulties in assessing the authenticity of the DNA sequences retrieved. We discuss how these difficulties can be addressed, particularly with regard to analyses of the Neandertal genome. We argue that only direct assays of DNA sequence positions in which Neandertals differ from all contemporary humans can serve as a reliable means to estimate human contamination. Indirect measures, such as the extent of DNA fragmentation, nucleotide misincorporations, or comparison of derived allele frequencies in different fragment size classes, are unreliable. Fortunately, interim approaches based on mtDNA differences between Neandertals and current humans, detection of male contamination through Y chromosomal sequences, and repeated sequencing from the same fossil to detect autosomal contamination allow initial large-scale sequencing of Neandertal genomes. This will result in the discovery of fixed differences in the nuclear genome between Neandertals and current humans that can serve as future direct assays for contamination. For analyses of other fossil hominins, which may become possible in the future, we suggest a similar 'boot-strap' approach in which interim approaches are applied until sufficient data for more definitive direct assays are acquired.
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aDNA samples typically have contamination from microbial DNA and present-day humans, which often represents the bulk of the DNA extracted from ancient remains.
“Moreover, there will typically be contamination from microbial DNA (modern or ancient), which often represents the bulk of the DNA extracted from ancient remains as well as contamination from present-day humans who have handled the sample [3].”
From <tt>SAFARI</tt> : pangenome alignment of ancient DNA using purine/pyrimidine encodings (2025) · cites this paper as [3]
In “MtDNA as an inroad to the Neandertal genome” (page unavailable), the paper says Neandertal DNA libraries contain at most a few percent Neandertal DNA, with the rest coming from microbes that colonized the bones. “Ancient DNA and authenticity” (page unavailable) calls human DNA a common contaminant of fossils and laboratory experiments. These passages support the contamination concern, but the microbial-majority finding is stated for Neandertal libraries rather than ancient remains generally, and the paper does not specifically attribute human contamination to people handling the sample. (LLM, conf=0.84)
Experimental — accuracy not yet measuredaDNA data tends to be very low-coverage.
“This entails that the data will tend to be very low-coverage.”
From <tt>SAFARI</tt> : pangenome alignment of ancient DNA using purine/pyrimidine encodings (2025) · cites this paper as [3]
The Autosomal contamination estimates section says one method requires relatively high genome coverage and substantial sequencing, but does not say ancient DNA datasets generally have very low coverage. The Conclusions and prospects section discusses the possibility of sequencing ancient genomes to high coverage. Searches for low coverage and limited sequencing depth found no passage establishing the claimed tendency. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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<tt>SAFARI</tt> : pangenome alignment of ancient DNA using purine/pyrimidine encodings
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“Moreover, there will typically be contamination from microbial DNA (modern or ancient), which often represents the bulk of the DNA extracted from ancient remains as well as contamination from present-day humans who have handled the sample [ 3 ].”
- Authors
- Green, R. E., Briggs, A. W., Krause, J., Prüfer, K., Burbano, H. A., Siebauer, M., Lachmann, M., & Pääbo, S.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- Max Planck Society (DE)
- Corresponding author
- Pääbo, Svante
- ORCID
- Venue
- The EMBO Journal
- Published
- 2009-08-06
- Volume
- 28
- Issue
- 17
- Pages
- 2494-2502
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2725275
- OpenAlex
- W2092369215
- Cited by
- 190
- References
- 46
- Citations by year
- 2026: 3 · 2025: 19 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 9 · 2020: 13 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 16 · 2015: 10 · 2014: 19 · 2013: 9 · 2012: 8
- FWCI
- 19.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by-nc-nd)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Max-Planck-Gesellschaft
- Topics
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- ancient DNA, human contamination, contamination detection, mitochondrial DNA, Y chromosome, fossil hominins, derived allele frequency, DNA fragmentation
- MeSH terms
- Animals, Base Sequence, DNA, DNA, Mitochondrial, Fossils, Humans, Phylogeny, Genetic Variation, Hominidae, Genome, Sequence Analysis, DNA, Evolution, Molecular
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