'Black Death' Genome Analysis Shows Links Alive Today

Reconstruction is complete on more than 99% of the genome of the Yersinia pestis strain responsible for the plague that swept Europe in the mid-14th century, killing nearly half of the population, an international team of researchers reported.

A phylogenetic analysis of the reconstructed genome revealed that the plague pathogen is just two substitutions away from the common ancestor of all modern strains of Y. pestis, Johannes Krause, PhD, of the University of Tübingen in Germany, and an international team of colleagues wrote online in Nature.

"It's extremely closely related" to strains circulating today, Krause said on a Tuesday conference call with reporters.

The work of Krause and colleagues marks the first time an historical pathogen has been reconstructed from skeletal remains -- in this case from Black Death victims interred at the East Smithfield mass burial site in London from 1348 to 1350.

Krause said that the evidence points toward the Black Death as the primary event responsible for introducing the ancestor to currently circulating strains of Y. pestis into the human population.

"That, of course, questions some of the historical disease and plague outbreaks such as the Justinian Plague ... and suggests that they were either caused by a Yersinia pestis strain which is completely extinct and didn't leave any descendants which are still around today, or [were] caused by a different pathogen that we have no information about yet," he said.

The researchers recently reported on a technique that could be used to confirm the authenticity of ancient pathogen DNA, a proof-of-principle study that involved just 0.002% of the total genome.

In the current study, they reconstructed nearly the entire genome of the plague pathogen using microarray enrichment and high-throughput sequencing of DNA extracted from the roots and crowns of four teeth taken from Black Death victims.

One of the study co-authors, Hendrik Poinar, PhD, of McMaster University in Hamilton, Ontario, said on the conference call that the team did not identify any substitutions in the ancient genome that are not found in strains that exist today, although the exact collection of substitutions is not found in any single contemporary strain.

He said that it is unclear which of these particular substitutions can explain why the ancient version of the bacterium was so deadly, adding that antibiotic resistance experts have determined that modern antibiotics -- including tetracyclines and fluoroquinolones -- would be able to kill it.

Krause speculated that other factors, such as the climate shifting to become cooler and wetter during the medieval period, and the presence of co-circulating pathogens, might have played a role.

"But I think a large contribution is the fact that it was the first time that it was unleashed," he said.

The researchers theorized that molecular changes in pathogens are just one of many factors contributing to changing infectious disease prevalence and severity, "where genetics of the host population, climate, vector dynamics, social conditions, and synergistic interactions with concurrent diseases should be foremost in discussions of population susceptibility to infectious disease and host-pathogen relationships with reference to Y. pestis infections."

The study was funded by the Carl Zeiss Foundation, the Human Genetics department of the Medical faculty in Tübingen, the Canada Research Chairs program, the Canadian Institutes of Health Research, the Social Science and Humanities Research Council of Canada, the Michael G. DeGroote Institute for Infectious Disease Research, an Early Research award from the Ontario Ministry of Research and Education, the Natural Sciences and Engineering Research Council of Canada, the James S. McDonnell Foundation, and the University at Albany Research Foundation and Center for Social and Demographic Analysis and the Wenner-Gren Foundation.


Primary source: Nature
Source reference:
Bos K, et al "A draft genome of Yersinia pestis from victims of the Black Death" Nature 2011; DOI: 10.1038/nature10549.



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