Thursday, October 13, 2011

Mysteries of the Black Death solved by genome sequencing


Plague is a deadly infectious disease that still circulates today, with thousands of cases being reported to the World Health Organization each year. It is generally accepted that plague has broken out into a pandemic at least three times over the course of history--the Justinian Plague (AD 541-542), the Black Death (1347-1351), and the Third Pandemic (1855-1959). There has been much great debate among the scientific community over whether Yersinia pestis, the bacteria responsible for modern plague, could have actually caused these historical pandemics, particularly the Black Death which very well may have reduced Europe's population by half.

Many researchers had valid arguments against Y. pestis being the culprit of the Black Death. Symptoms such as buboes and a terrible stench accompanying infection seem to have diminished or disappeared altogether by modern times. Perhaps more importantly, the epidemiology of the disease seems to have made a major shift--outbreaks in the early 1900s saw a death rate of less than 1%, while the Black Death was fatal at least 30% of the time. However, an August 2011 NY Times article revealed that Y. pestis had been recovered from East Smithfield cemetery in London, where burial was reserved for victims of the Black Death, confirming Y. pestis was the culprit of the outbreak that decimated the globe in the 14th Century.

Published in Nature October 12th, scientists now have a draft genome of the ancient Yersinia pestis, the news of which is summarized nicely in this NY Times article. Not only is this a landmark because of what it might reveal about the evolution of one of the deadliest pathogens of all time, but it is the first time the genome of any ancient pathogen has been sequenced. The DNA was again recovered from East Smithfield and used to construct a phylogenetic tree as well as for comparison studies with modern Y. pestis and its ancestor, Yersinia pseudotuberculosis. The ancient East Smithfield sequence was placed near the node of all extant infectious Y. pestis, and was shown to have no unique derived positions from its ancestral strain. Additionally, only 97 single nucleotide differences were observed in the 4.6 million bp genome between ancient and modern Y. pestis. The researchers suggest that the perceived increased virulence of the Black Death may be a result of a network of factors including climate, social conditions, and disease vectors, but most likely not bacterial phenotype.

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