TY - JOUR

T1 - A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex

AU - Sabin, Susanna

AU - Herbig, Alexander

AU - Vågene, Åshild J.

AU - Ahlström, Torbjörn

AU - Bozovic, Gracijela

AU - Arcini, Caroline

AU - Kühnert, Denise

AU - Bos, Kirsten I.

PY - 2020

Y1 - 2020

N2 - 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 modernMycobacterium tuberculosiscomplex (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 coverageM.tuberculosisgenome. 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.

AB - 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 modernMycobacterium tuberculosiscomplex (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 coverageM.tuberculosisgenome. 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.

KW - Tuberculosis

KW - Ancient DNA

KW - Mycobacterium tuberculosis

KW - Molecular dating

KW - Metagenomics

KW - MYCOBACTERIUM-TUBERCULOSIS

KW - TIME DEPENDENCY

KW - GENOME SEQUENCE

KW - DNA

KW - CAVE

KW - EVOLUTIONARY

KW - EPIDEMIC

KW - LIGURIA

KW - PROGRAM

U2 - 10.1186/s13059-020-02112-1

DO - 10.1186/s13059-020-02112-1

M3 - Journal article

C2 - 32778135

VL - 21

JO - Genome Biology (Online Edition)

JF - Genome Biology (Online Edition)

SN - 1474-7596

M1 - 201

ER -