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Cited by 97Tuberculosis Research and EpidemiologyPaleopathology and ancient diseasesForensic and Genetic Research

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A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex

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Sabin, Susanna, Herbig, Alexander, Vågene, Åshild J., Ahlström, Torbjörn, Bozovic, Gracijela, Arcini, Caroline, Kühnert, Denise, Bos, Kirsten I.·2020·Genome Biology
DOI 10.1186/s13059-020-02112-1PMC PMC7418204

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Abstract

Background: Although tuberculosis accounts for the highest mortality from a bacterial infection on a global scale, questions persist regarding its origin. One hypothesis based on modern Mycobacterium tuberculosis complex (MTBC) genomes suggests their most recent common ancestor followed human migrations out of Africa approximately 70,000 years before present. However, studies using ancient genomes as calibration points have yielded much younger dates of less than 6000 years. Here, we aim to address this discrepancy through the analysis of the highest-coverage and highest-quality ancient MTBC genome available to date, reconstructed from a calcified lung nodule of Bishop Peder Winstrup of Lund (b. 1605–d. 1679). Results: A metagenomic approach for taxonomic classification of whole DNA content permitted the identification of abundant DNA belonging to the human host and the MTBC, with few non-TB bacterial taxa comprising the background. Genomic enrichment enabled the reconstruction of a 141-fold coverage M . tuberculosis genome. In utilizing this high-quality, high-coverage seventeenth-century genome as a calibration point for dating the MTBC, we employed multiple Bayesian tree models, including birth-death models, which allowed us to model pathogen population dynamics and data sampling strategies more realistically than those based on the coalescent. Conclusions: The results of our metagenomic analysis demonstrate the unique preservation environment calcified nodules provide for DNA. Importantly, we estimate a most recent common ancestor date for the MTBC of between 2190 and 4501 before present and for Lineage 4 of between 929 and 2084 before present using multiple models, confirming a Neolithic emergence for the MTBC.

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  • While the analyses of ancient pathogen genomes have shown plague to be older than expected, they suggest that the origins of the tuberculosis complex in humans may have evolved more recently (~3,000-6,000 years ago).

    “While the analyses of ancient pathogen genomes have shown plague to be older than expected, they suggest that the origins of the tuberculosis complex (M.tuberculosis and related strains) in humans may have evolved more recently (~3,000-6,000 years ago) [307][308] .”

    From Ancient DNA analysis (2021) · cites this paper as [307]

    The Discussion dates the common ancestor of known tuberculosis-complex diversity to approximately 2,000–6,000 years before present, supporting the claim of a relatively recent emergence but not its 3,000-year lower bound. The Discussion also cautions that a closely related ancestor may have infected humans before 6,000 years ago, so the estimate does not establish when tuberculosis-like infections in humans began. (LLM, conf=0.84)

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  • Ancient DNA analysis

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Metadata

Authors
Sabin, S., Herbig, A., Vågene, Å. J., Ahlström, T., Bozovic, G., Arcini, C., Kühnert, D., & Bos, K. I.
Affiliations
  • Max Planck Society (DE)
  • Lund University (SE)
  • National Historical Museums (SE)
  • Max Planck Institute of Geoanthropology (DE)
Corresponding author
Kühnert, Denise
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2020-08-10
Volume
21
Issue
1
Pages
201-201
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-020-02112-1
PMC
PMC7418204
OpenAlex
W3048218099
Cited by
97
References
14
Citations by year
2026: 17 · 2025: 15 · 2024: 15 · 2023: 16 · 2022: 17 · 2021: 7 · 2020: 7
FWCI
1.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lund University Publications (Lund University) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • Figshare (cc-by)
Funders
  • Max-Planck-Gesellschaft (na)
  • Erik Philip-Sörensen Foundation (na)
  • Crafoord Foundation (na)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Social Sciences › Arts and Humanities › Archeology (arts and humanities) › Paleopathology and ancient diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords
Mycobacterium tuberculosis complex, ancient DNA, birth-death model, Bayesian phylogenetics, lineage 4, DNA preservation
MeSH terms
Africa, Bayes Theorem, Humans, Lung, Mycobacterium tuberculosis, Phylogeny, Tuberculosis, Genome, Bacterial, History, 17th Century, Metagenomics, Phylogeography

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