Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis

Plague of Justinian

Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis

By David M. Wagner, Jennifer Klunk, Michaela Harbeck et al.

The Lancet: Infectious Diseases, Volume 14, No. 4 (2014)

Plague of Justinian

Background: Yersinia pestis has caused at least three human plague pandemics. The second (Black Death, 14–17th centuries) and third (19–20th centuries) have been genetically characterised, but there is only a limited understanding of the first pandemic, the Plague of Justinian (6–8th centuries). To address this gap, we sequenced and analysed draft genomes of Y pestis obtained from two individuals who died in the first pandemic.

Methods:  Teeth were removed from two individuals (known as A120 and A76) from the early medieval Aschheim-Bajuwarenring cemetery (Aschheim, Bavaria, Germany). We isolated DNA from the teeth using a modified phenol-chloroform method. We screened DNA extracts for the presence of the Y pestis-specific pla gene on the pPCP1 plasmid using primers and standards from an established assay, enriched the DNA, and then sequenced it. We reconstructed draft genomes of the infectious Y pestis strains, compared them with a database of genomes from 131 Y pestis strains from the second and third pandemics, and constructed a maximum likelihood phylogenetic tree.

Findings: Radiocarbon dating of both individuals (A120 to 533 AD [plus or minus 98 years]; A76 to 504 AD [plus or minus 61 years]) places them in the timeframe of the first pandemic. Our phylogeny contains a novel branch (100% bootstrap at all relevant nodes) leading to the two Justinian samples. This branch has no known contemporary representatives, and thus is either extinct or unsampled in wild rodent reservoirs. The Justinian branch is interleaved between two extant groups, 0.ANT1 and 0.ANT2, and is distant from strains associated with the second and third pandemics.

Interpretation: We conclude that the Y pestis lineages that caused the Plague of Justinian and the Black Death 800 years later were independent emergences from rodents into human beings. These results show that rodent species worldwide represent important reservoirs for the repeated emergence of diverse lineages of Y pestis into human populations.

Introduction: Between 541 and 543 AD, the Plague of Justinian, traditionally regarded as the first of three human plague pandemics, spread from either central Asia or Africa across the Mediterranean basin into Europe, killing an estimated 100 million people according to the contemporary scholar Procopius (although this history is disputed), contributing to the end of theRoman empire, and marking the transition from the classical to the Medieval period. Subsequent outbreaks of this disease occurred in 8–12 year cycles for two centuries after the initial epidemic with estimated mortality of 15–40%. Although suspected to have been caused by Yersinia pestis, uncertainties in historical epidemiology have led some researchers to propose other pathogens as the causative agent of the Plague of Justinian, such as an influenza virus. However, the symptoms described by Procopius are very similar to those later reported during the second pandemic of the 14–17th centuries (ie, the Black Death), from which Y pestis has been genomically characterised, implicating this bacterial species as the infectious agent of the first pandemic.

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