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

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

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

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Hershkovitz, Israel, Donoghue, Helen D., Minnikin, David E., Besra, Gurdyal S., Lee, Oona Y-C., Gernaey, Angela M., Galili, Ehud, Eshed, Vered, Greenblatt, Charles L., Lemma, Eshetu, Bar-Gal, Gila Kahila, Spigelman, Mark·2008·PLoS ONE
DOI 10.1371/journal.pone.0003426PMC PMC2565837
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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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Figures

Figure 1 Map of Atlit-Yam site in the North Bay of Atlit, 10 km south of Haifa (34°56′ E, 32°42.5′ N). Inset shows general geographical location.
Figure 1 Map of Atlit-Yam site in the North Bay of Atlit, 10 km south of Haifa (34°56′ E, 32°42.5′ N). Inset shows general geographical location.CC BY · PubMed Central
Figure 2 Paleopathological lesions on Neolithic infant bones. A. Endocranial surface of the infant showing marked engravings (serpens endocrania symmetrica, SES), which indicate chronic respiratory malfunction, and are usually associated with tuberculosis. B. Fragment of long bone of the infant. Note the intensive bone remodeling (hypertrophic osteoarthropathy, HOA) at the surface on the right side. C. Higher magnification of the HOA on the infant bone.
Figure 2 Paleopathological lesions on Neolithic infant bones. A. Endocranial surface of the infant showing marked engravings (serpens endocrania symmetrica, SES), which indicate chronic respiratory malfunction, and are usually associated with tuberculosis. B. Fragment of long bone of the infant. Note the intensive bone remodeling (hypertrophic osteoarthropathy, HOA) at the surface on the right side. C. Higher magnification of the HOA on the infant bone.CC BY · PubMed Central
Figure 3 Detection of Mycobacterium tuberculosis mycolic acid pyrenebutyric acid-pentafluorobenzyl (PBA-PFB) derivatives by reverse phase fluorescence high performance liquid chromatography (HPLC), from the Neolithic woman and infant. The characteristic tight envelopes of peaks are the total mixture of homologues for the different α-, methoxy- and ketomycolates. The Y-axis in the profiles represents absorbance; absolute values of the mycolates detected are shown in Supporting Table 5.
Figure 3 Detection of Mycobacterium tuberculosis mycolic acid pyrenebutyric acid-pentafluorobenzyl (PBA-PFB) derivatives by reverse phase fluorescence high performance liquid chromatography (HPLC), from the Neolithic woman and infant. The characteristic tight envelopes of peaks are the total mixture of homologues for the different α-, methoxy- and ketomycolates. The Y-axis in the profiles represents absorbance; absolute values of the mycolates detected are shown in Supporting Table 5.CC BY · PubMed Central

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Research works printed but not linked: 1

  1. DE Minnikin, 1987, Mass spectrometric analysis of multimethyl branched fatty acids and phthiocerols from clinically-significant mycobacteria., Proc Jap Soc Med Mass Spectrom, 12, 23

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Metadata

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.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2008-10-15
Volume
3
Issue
10
Pages
e3426
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0003426
PMC
PMC2565837
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
Licence
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 (arts and humanities) › Paleopathology and ancient diseases
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Social Sciences › Archeology › 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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