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NIAID Grantees Trace Evolution of the Plague

NIAID-funded scientists recently completed a study on the evolution of Yersinia pestis, the bacterium that causes the plague. They found that Y. pestis evolved in China and spread through multiple migrations to other parts of the world, leading to country-specific lineages that can be traced genetically. “These results will give us the tools to detect, understand, and explain why and how plagues occur and cause such high morbidity,” said Suman Mukhopadhyay, Ph.D., of NIAID’s Bacteriology and Mycology Branch.

The study was conducted by the NIAID Genome Sequencing Centers for Infectious Diseases (GSC), with genetic sequencing done at the J. Craig Venter Institute (JCVI), and analysis performed at the Institute for Genome Sciences at the University of Maryland School of Medicine. The article was published online in October 2010, in the journal Nature Genetics.

Assembling Plague Genomes From Around the World

The researchers analyzed one of the largest global collections ever assembled of bacteria that cause plague, beginning by sequencing the genomes of a diverse set of 11 Y. pestis strains. They then compared the genomes of these 11 isolates and six more that had been previously sequenced.

“The phylogenomic analysis of these 17 genomes yielded the cataloguing of hundreds of variable sites in the DNA, which were later used to examine a global collection of 286 additional isolates,” explained Mark Eppinger, Ph.D., of the University of Maryland, a coauthor on the study. Using the rare polymorphisms that they discovered in this pathogen, they reconstructed a detailed history of past plague pandemics. “Obtaining the additional genome sequences was essential in characterizing the evolution of this devastating human pathogen,” said Dr. Eppinger.

Following Historical Trade Routes To Explain Pandemics

The researchers also found strong geographic clustering of Y. pestis populations, with each population in a different region of the world. Tracing the evolutionary tree back through time, they concluded that the bacterium evolved in China and then spread to other areas, since descendants of the Chinese strain were found all over the world. They were also able to trace multiple radiations of Y. pestis from China via historic trade routes and connect these to historical pandemics. For example, the data support historical records that plague was imported to the United States in 1899 on a ship from Hong Kong that docked in Hawaii and arrived in San Francisco. The most recent plague pandemic, in 1894, spread to India and from there to many parts of the globe, including the United States, which was infected by a single radiation still persisting today in wild rodents.

In the future, the investigators plan to look more closely at Y. pestis strains from regions that are currently undersampled, like Africa or the former Soviet Union. The resulting framework of the plague bacterium will be useful for future surveillance efforts and outbreak preparedness. In addition, this phylogenomic methodology can serve as a model for the control of other epidemic diseases, such as Salmonella, E. coli, and influenza.


G Morelli et al. Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nature Genetics. DOI: 10.1038/ng.705 (2010).

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Last Updated January 03, 2011