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Introduction
Plague is caused by the bacteria Yersinia pestis and is being directly transmitted through human-to-human contact (pneumonic plague) or via fleas as a common vector (bubonic or septicemic plague) (Treille and Yersin, 1894). Three historic human plague pandemics have been documented: (1) the First Pandemic, which started with the Plague of Justinian (541–544 AD), but continued intermittently until ~750 AD; (2) the Second Pandemic, which began with the Black Death in Europe (1347–1351 AD) and included successive waves, such as the Great Plague (1665–1666 AD), until the 18th century; (3) the Third Pandemic, which emerged in China in the 1850s and erupted there in a major epidemic in 1894 before spreading across the world as a series of epidemics until the middle of the 20th century (Bos et al., 2011, Cui et al., 2013, Drancourt et al., 1998, Harbeck et al., 2013, Parkhill et al., 2001, Perry and Fetherston, 1997, Wagner et al., 2014). Earlier outbreaks such as the Plague of Athens (430–427 BC) and the Antonine Plague (165–180 AD) may also have occurred, but there is no direct evidence that allows confident attribution to Y. pestis (Drancourt and Raoult, 2002, McNeill, 1976).
The consequences of the plague pandemics have been well-documented and the demographic impacts were dramatic (Little et al., 2007). The Black Death alone is estimated to have killed 30%–50% of the European population. Economic and political collapses have also been in part attributed to the devastating effects of the plague. The Plague of Justinian is thought to have played a major role in weakening the Byzantine Empire, and the earlier putative plagues have been associated with the decline of Classical Greece and likely undermined the strength of the Roman army.
Molecular clock estimates have suggested that Y. pestis diversified from the more prevalent and environmental stress-tolerant, but less pathogenic, enteric bacterium Y. pseudotuberculosis between 2,600 and 28,000 years ago (Achtman et al., 1999, Achtman et al., 2004, Cui et al., 2013, Wagner et al., 2014). However, humans may potentially have been exposed to Y. pestis for much longer than the historical record suggests, though direct molecular evidence for Y. pestis has not been obtained from skeletal material older than 1,500 years (Bos et al., 2011, Wagner et al., 2014). The most basal strains of Y. pestis (0.PE7 clade) recorded to date were isolated from the Qinghai-Tibet Plateau in China in 1961–1962 (Cui et al., 2013).
We investigated the origin of Y. pestis by sequencing ancient bacterial genomes from the teeth of Bronze Age humans across Europe and Asia. Our findings suggest that the virulent, flea-borne Y. pestis strain that caused the historic bubonic plague pandemics evolved from a less pathogenic Y. pestis lineage infecting human populations long before recorded evidence of plague outbreaks. |
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