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

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.Results - Pathogen identification - Genomic enrichment and reconstruction - Phylogeny and dating Discussion Conclusions Methods - Lung nodule identification - Sampling and extraction - Library preparation and shotgun screening sequencing - Pathogen identification and authentication - In-solution capture probe design - UDG library preparation and in-solution capture - Genomic reconstruction, heterozygosity, and SNP calling - Phylogenetic analysis - Bayesian phylogenetic analysis of full MTBC and L4 dataset

A genomic and historical synthesis of plague in 18th century Eurasia

Plague continued to afflict Europe for more than five centuries after the Black Death. Yet, by the 17th century, the dynamics of plague had changed, leading to its slow decline in Western Europe over the subsequent 200 y, a period for which only one genome was previously available. Using a multidisciplinary approach, combining genomic and historical data, we assembled Y. pestis genomes from nine individuals covering four Eurasian sites and placed them into an historical context within the established phylogeny. CHE1 (Chechnya, Russia, 18th century) is now the latest Second Plague Pandemic genome and the first non-European sample in the post-Black Death lineage. Its placement in the phylogeny and our synthesis point toward the existence of an extra-European reservoir feeding plague into Western Europe in multiple waves. By considering socioeconomic, ecological, and climatic factors we highlight the importance of a noneurocentric approach for the discussion on Second Plague Pandemic dynamics in Europe