Cited by 543Paleopathology and ancient diseasesTuberculosis Research and EpidemiologyArchaeology and ancient environmental studies

Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean

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Abstract

BACKGROUND: Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis. It has no environmental reservoir and is believed to have co-evolved with its host over millennia. This is supported by skeletal evidence of the disease in early humans, and inferred from M. tuberculosis genomic analysis. Direct examination of ancient human remains for M. tuberculosis biomarkers should aid our understanding of the nature of prehistoric tuberculosis and the host/pathogen relationship. METHODOLOGY/PRINCIPAL FINDINGS: We used conventional PCR to examine bone samples with typical tuberculosis lesions from a woman and infant, who were buried together in the now submerged site of Atlit-Yam in the Eastern Mediterranean, dating from 9,250-8,160 years ago. Rigorous precautions were taken to prevent contamination, and independent centers were used to confirm authenticity of findings. DNA from five M tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex. CONCLUSIONS/SIGNIFICANCE: Human tuberculosis was confirmed by morphological and molecular methods in a population living in one of the first villages with evidence of agriculture and animal domestication. The widespread use of animals was not a source of infection but may have supported a denser human population that facilitated transmission of the tubercle bacillus. The similarity of the M. tuberculosis genetic signature with those of today gives support to the theory of a long-term co-existence of host and pathogen.

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  • The identification of M. tuberculosis from an individual approximately 2,000 years ago is consistent with our current understanding of Mycobacterium infection and transmission between humans and in humans and domesticated animals.

    “The identification of M. tuberculosis from an individual approximately 2,000 years ago is consistent with our current understanding of Mycobacterium infection and transmission between humans and in humans and domesticated animals [40].”

    From Molecular Exploration of the First-Century Tomb of the Shroud in Akeldama, Jerusalem (2009) · cites this paper as [40]

    The Introduction reports M. tuberculosis in human remains, and the Discussion links its transmission to denser human populations. But the studied remains date to 9,250–8,160 years ago, not approximately 2,000 years ago. The paper also says domesticated animals were not the source of infection in this population; it does not establish transmission between humans and domesticated animals. (LLM, conf=0.88)

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Authors
Hershkovitz, I., Donoghue, H. D., Minnikin, D. E., Besra, G. S., Lee, O. Y.-C., Gernaey, A. M., Galili, E., Eshed, V., Greenblatt, C. L., Lemma, E., Bar-Gal, G. K., & Spigelman, M.
Affiliations
  • University College London (GB)
  • University of Birmingham (GB)
  • University of Salford (GB)
  • Israel Antiquities Authority (IL)
  • Tel Aviv University (IL)
  • Hebrew University of Jerusalem (IL)
Corresponding author
Donoghue, Helen D.
Venue
PLoS ONE
Published
2008-10-15
Volume
3
Issue
10
Pages
e3426
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2052515110
Cited by
506
References
51
Citations by year
2026: 11 · 2025: 13 · 2024: 26 · 2023: 37 · 2022: 30 · 2021: 30 · 2020: 29 · 2019: 42 · 2018: 30 · 2017: 39 · 2016: 40 · 2015: 33 · 2014: 26 · 2013: 36 · 2012: 25
FWCI
167.98
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
Funders
  • Leverhulme Trust
  • Deutsche Forschungsgemeinschaft
  • Dan David Prize
Topics
  • Social Sciences › Arts and Humanities › Archeology › Paleopathology and ancient diseases
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Physical Sciences › Earth and Planetary Sciences › Paleontology › Archaeology and ancient environmental studies
Keywords
Mycobacterium tuberculosis, Neolithic, ancient DNA, host-pathogen coevolution, tuberculosis transmission, animal domestication, human remains, Eastern Mediterranean
MeSH terms
Adult, Bone and Bones, DNA, Bacterial, Female, Humans, Infant, Mycobacterium tuberculosis, Tuberculosis, Polymerase Chain Reaction, Mediterranean Region, History, Ancient

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