Researchers reconstruct genome of the Black Death

By Michelle Donovan, October 13, 2011

    A skull from the East Smithfield plague pits in London, located under what is now the Royal Mint. Researchers announced today that they have sequenced the entire genome of the Black Death, one of the most devastating epidemics in human history. Photo by Museum of London.
An international team - led by researchers at McMaster University and the University of
Tubingen in Germany - has sequenced the entire genome of the Black Death, one of the
most devastating epidemics in human history.

This marks the first time scientists have been able to draft a reconstructed genome of
any ancient pathogen, which will allow researchers to track changes in the pathogen's
evolution and virulence over time. This work - currently published online in the scientific
journal Nature - could lead to a better understanding of modern infectious diseases.

Geneticists Hendrik Poinar and Kirsten Bos of McMaster University and Johannes Krause
and Verena Schuenemann of the University of Tubingen collaborated with Brian Golding
and David Earn of McMaster, Hernan A. Burbano and Matthias Meyer of the Max Planck
Institute for Evolutionary Anthropology and Sharon DeWitte of the University of South
Carolina, among others.

In a separate study published recently, the team described a novel methodological
approach to pull out tiny degraded DNA fragments of the causative agent of the Black
Death, and showed that a specific variant of the Yersinia pestis bacterium was
responsible for the plague that killed 50 million Europeans between 1347 and 1351.

After this success, the next major step was to attempt to "capture" and sequence the
entire genome, explained Poinar, associate professor and director of the McMaster
Ancient DNA Centre and investigator with the Michael G. DeGroote Institute of Infectious
Disease Research, also at McMaster.

"The genomic data show that this bacterial strain, or variant, is the ancestor of all
modern plagues we have today worldwide. Every outbreak across the globe today stems
from a descendant of the medieval plague," he said. "With a better understanding of the
evolution of this deadly pathogen, we are entering a new era of research into infectious

"Using the same methodology, it should now be possible to study the genomes of all
sorts of historic pathogens," said Krause, one of the lead authors of the study. "This will
provide us with direct insights into the evolution of human pathogens and historical

The direct descendants of the same bubonic plague continue to exist today, killing
some 2,000 people each year.

"We found that in 660 years of evolution as a human pathogen, there have been
relatively few changes in the genome of the ancient organism, but those changes,
however small, may or may not account for the noted increased virulence of the bug
that ravaged Europe," said Poinar. "The next step is to determine why this was so

Major technical advances in DNA recovery and sequencing have dramatically expanded
the scope of genetic analysis of ancient specimens, opening new horizons in the
understanding of emerging and re-emerging infections.

DeWitte, Bos and Schuenemann analyzed skeletal remains from victims buried in the
East Smithfield "plague pits" in London, located under what is now the Royal Mint. By
targeting promising specimens - which had been pre-screened for the presence of Y.
pestis - from the dental pulp of five bodies, they were able to extract, purify and enrich
specifically for the pathogen's DNA, thereby decreasing the background DNA consisting
of human, fungal and other non-plague DNA.

Linking the 1349-1350 dates of the skeletal remains to the genomic data allowed the
researchers to calculate the age of the ancestor of the Yersinia pestis that caused the
medieval plague. This date coalesced sometime between the 12th and 13th centuries,
indicating that earlier plagues such as the Justinian plague of the 6th Century - once
thought to have been caused by the same pathogen - was likely caused by another, yet
to be determined. The Justinian plague spread across the Eastern Roman Empire, killing
an estimated 100 million people worldwide.

The research was funded by the Canadian Institutes for Health Research, the Social
Sciences and Humanities Research Council, Canada Research Chairs, an Early Researcher
Award from the Ontario Government, the Michael G. DeGroote Institute of Infectious
Disease Research, the Wenner Gren foundation, and the Medical Faculty at University of