Genes reveal recent origin for the plague.

One bacterium, carried by fleas, is the plague-causing microbe behind the Black Death, which slew 25 million people in the Middle Ages. Another, shed in rodent feces that can contaminate food, simply triggers a week or two of fever, vomiting, and diarrhea in people.

A new genetic analysis confirms that despite their dramatic differences, these two microbes share a remarkably close ancestry, like parent and child. Yersinia pestis, which causes bubonic plague, is a relatively recent offshoot, perhaps only 1,500 to 20,500 years old, of the less dangerous Yersinia pseudotuberculosis, Mark Achtman of the Max Planck Institute for Molecular Genetics in Berlin and his colleagues report in the Nov. 23 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

Historians have documented three worldwide epidemics of the plague. The first started during the reign of the Byzantine emperor Justinian, around A.D. 542. The second, the Black Death, swept from Asia into Europe during the 14th century. The third broke out in China just before the turn of this century.

Some scholars have argued that Y pestis has existed for millions of years and only betrayed its presence when human populations grew dense enough to sustain epidemics. However, there's little scientific data that establishes an age for the microbe, notes Achtman. To address that issue, he joined forces with Elisabeth Carniel of the Pasteur Institute in Paris. She and her colleagues maintain and study a collection of Y pestis strains from around the world.

The researchers compared the DNA sequences of six fundamental genes among 36 strains. "There was no diversity. All the sequences were identical. That's a highly unusual finding and difficult to explain, unless you say that there simply hasn't been time for [mutations] to accumulate," says Achtman.

If Y. pestis experiences mutations at the same rate as the well-studied bacterium Escherichia coli, then it arose sometime within the past 20,500 years, the researchers calculate. If it was any older, it should show some diversity in the genes examined, they say.

"This age estimate will be controversial," admits Achtman, noting that scientists disagree on whether they can use the mutation rate of one bacterium to gauge the age of another.

The scientists also compared the Y. pestis genes with those from Y. pseudo tuberculosis. They found so few differences in the DNA that the investigators argue that the microbes aren't distinct species. Two decades ago, less detailed DNA comparisons between the two bacteria also led scientists to suggest eliminating the Y. pestis designation, but tradition prevailed. "There's no justification, except for its medical significance, for the term Yersinia pestis," says Achtman.

"For a long time, it's been assumed that the bacterium that causes plague and Y. pseudotuberculosis were closely related, but no one has done a molecular analysis like Achtman and his colleagues did," says Tom G. Schwan of the National Institute of Allergy and Infectious Disease in Rocky Mountain, Colo.

Understanding its divergence from Y. pseudotuberculosis may help scientists explain how Y. pestis evolved into such a dangerous microbe. Investigators have nearly finished sequencing the plague bacterium's genes. They suspect that the largest difference between the two microbes stems from the two extra plasmids, or rings of DNA, that only Y. pestis possesses.

"We're in a perfect position to make some significant advances now that the genome of Y. pestis is being completed," says Schwan.