In Ancient DNA, Evidence of Plague Much Earlier Than Previously Known

Bacteria can change history.

In the 14th century, a microbe called Yersinia pestis caused an epidemic of plague known as the Black Death that killed off a third or more of the population of Europe. The long-term shortage of workers that followed helped bring about the end of feudalism.

Historians and microbiologists alike have searched for decades for the origins of plague. Until now, the first clear evidence of Yersinia pestis infection was the Plague of Justinian in the 6th century, which severely weakened the Byzantine Empire.

But in a new study, published on Thursday in the journal Cell, researchers report that the bacterium was infecting people as long as 5,000 years ago.

Exactly what those early outbreaks were like is impossible to know. But the authors of the new study suggest that plague epidemics in the Bronze Age may have opened the doors to waves of migrants in regions decimated by disease.

“To my mind, this leaves little doubt that this has played a major role in those population replacements,” said Eske Willerslev, a co-author of the new study and the director of the Center for GeoGenetics at the University of Copenhagen.

David M. Wagner, a microbial geneticist at Northern Arizona University who was not involved in the study, said that the new research should prompt other scientists to look at mysterious outbreaks in early history, such as the epidemic that devastated Athens during the Peloponnesian War. “It opens up whole new areas of research,” he said.

The new study arose from previous research by Dr. Willerslev and his colleagues. They were able to extract human DNA from101 bones found in Europe and Asia, ranging in age from about 3,000 to 5,000 years old.

As they reported in June, the genetic profiles of people during that 2,000-year period changed with surprising abruptness. About 4,500 years ago, for example, the DNA of Europe’s inhabitants suddenly took on a strong resemblance to that of the Yamnaya, a nomadic people from western Russia.

Wondering what could have triggered such a shift, Dr. Willerslev and his colleagues realized they could test one hypothesis: that epidemics had decimated some populations, allowing new groups to establish themselves.

When researchers search for ancient human genetic material in a piece of bone, they begin by retrieving all the DNA in the sample. Most of it is not human, belonging instead to bacteria and other microbes that colonize bones after death.

Once scientists have gathered all the DNA, they assemble the genetic fragments into larger pieces and try to match them to sequences already identified in earlier research. Normally they set aside microbial DNA to focus on the human material.

Dr. Willerslev and his colleagues wondered if some of the nonhuman DNA they had collected from Bronze Age remains might belong to pathogens. They decided to look for traces of Yersinia pestis, even though the earliest evidence of the infection dates to thousands of years later.

“Plague was just a long shot,” said Dr. Willerslev.

But sometimes long shots pay off. Of 101 Bronze Age individuals, the researchers found Yersinia pestis DNA in seven. Plague DNA was present in teeth recovered from sites stretching from Poland to Siberia.

By comparing the ancient Yersinia to more recent strains, the scientists also were able to reconstruct its evolutionary history.

Plague can take several different forms. In bubonic plague, the most common, the bacteria invade the lymphatic system. Left untreated, it can kill a victim within days.

The infection is spread by fleas hopping between rats and humans. But 5,000 years ago, Dr. Willerslev and his colleagues found, Yersinia pestis didn’t yet have a gene known to be essential for survival in fleas.

The bacterium did have many of the genes that make it deadly to humans. Dr. Wagner suggested that people may have become infected with plague in ancient times not by fleas, but bybreathing in the microbes or by hunting infected rodents for food.

After acquiring the ability to infect fleas, Yersinia pestis may have begun to spread more readily from one rodent to another, eventually causing widespread epidemics. “It really says something about the rapid evolution of pathogens,” said Dr. Wagner.

Hendrik N. Poinar, a geneticist at McMaster University who was not involved in the study, found this evolutionary scenario persuasive — “a slam dunk,” he said. But he isn’t convinced that huge outbreaks of primitive plague rocked ancient societies and questioned whether the bacteria could have spread quickly without infecting fleas.

“It is speculation as to whether these strains were responsible for high mortality rates in the Bronze Age,” he said.

Dr. Willerslev and his colleagues are now looking for more clues to how the plague affected the Bronze Age world — as well as other pathogens that may have left behind genetic traces. He is now grateful that he and his colleagues didn’t simply throw out all their nonhuman DNA.

“It was just annoying waste lying there that we had to bully our way through,” said Dr. Willerslev. “Now it’s not waste anymore. It’s a potential gold mine.”