Ancient tooth DNA reveals how ‘cold sore’ herpes virus has evolved

Researchers found ancient herpes DNA in the teeth of a man from the eighteenth century who was a fervent pipe smoker.Credit: Dr Barbara Veselka

Ancient DNA extracted from the teeth of humans who lived long ago is yielding new information about pathogens past and present.

In one of the latest studies, researchers uncovered and sequenced ancient herpes genomes for the first time, from the teeth of long-dead Europeans. The strain of herpes virus that causes lip sores in people today — called HSV-1 — was once thought to have emerged in Africa more than 50,000 years ago. But the new data, published in Science Advances on 27 July1indicate that its origin was much more recent: around 5,000 years ago during the Bronze Age.

The findings hint that changing cultural practices during the Bronze Age — including the emergence of romantic kissing — could have factored into HSV-1’s meteoric rise.

This and other studies related to tooth-extracted DNA are leading to surprising insights into our shared history with disease, says Christiana Scheib, an archaeomolecular biologist at the University of Tartu in Estonia. “All of the pathogens we have today were once novel infections,” she says. “It’s important to study ancient DNA so we can understand these past experiences and keep future generations safe from epidemics.”

Breakthroughs in bones

Teeth are treasure chests for ancient DNA because of their ability to protect biological molecules from degradation. In the past decade, scientists have used increasingly powerful sequencing technologies to reconstruct the genomes of long-dead humans and animals — the oldest being a mammoth that died 1.6 million years ago — using DNA found in their teeth.

In the process, they have also sorted through the genetic material of bacteria and viruses preserved in teeth. Molars, incisors and the like have blood vessels in their roots, so when a person or animal dies, these bones become repositories for whatever pathogens were moving through their bloodstream at the time of death.

The realization that teeth are caches for pathogen DNA has opened the study of ancient diseases to “a completely different kind of knowledge than what we could have accessed before”, says Martin Sikora, an ancient-genomics researcher at the University of Copenhagen in Denmark.

This genetic information has provided researchers with molecular evidence to pinpoint when and where pathogens were at a given time, Sikora says. In 2013, scientists used DNA extracted from teeth to confirm that the Justinian plague, which swept across the Mediterranean and northern Europe in the sixth century, was the first major outbreak of the plague bacteria Yersinia pestis2. And in June, a different group of researchers reported that the strain of Y. pestis that launched the Black Death — which killed upwards of 60% of people in some parts of Eurasia in the fourteenth century — probably evolved in modern-day Kyrgyzstan, on the basis of DNA from teeth found in that region3.

Sifting through remains

Studying ancient DNA can also help researchers to learn about the history of less deadly pathogens, such as the strain of oral herpes that has infected about two-thirds of the global population under age 50 today. In 2016, Scheib and her colleagues were looking for traces of Y. pestis in the 600-year-old tooth of a teen who died at St. John’s Hospital in Cambridgeshire, UK, when they stumbled across genetic sequences that seemed to match those of HSV-1.

Until that point, “there was no published ancient herpes DNA at all”, she says. The oldest herpes genome on record had been isolated from someone living in New York in 1925. The discovery led Scheib and her colleagues to look for signs of herpes in other remains. For this, the team needed to find people who had died with active infections. HSV-1 spends most of its time hiding in the nervous system of its host. But during times of stress, the virus moves into the bloodstream and flares up into ‘cold’ sores.

After sorting through dozens of remains, the researchers eventually found and extracted herpes DNA from the teeth of three people who died with active infections, including a young woman buried outside modern-day Cambridge, UK, in the sixth century.

By evaluating the genetic mutations that evolved among the four ancient genomes and comparing them with modern HSV-1 strains, the researchers deduced that they all had a common ancestor that popped up around 5,000 years ago. Before this, different versions of herpes were circulating, Scheib says. But HSV-1 evolved to ruthlessly outcompete them.

Kiss and tell

Exactly what led this new variety of herpes to be more successful than older versions is still unclear. But Scheib says the team’s analysis suggests that HSV-1 emerged during a period of intense migration during the Bronze Age, when it could have hitched a ride with people as they moved into Europe from the steppe grasslands of Eurasia.

And it might also have spread with the growing practice of romantic kissing, which was invented around 3,500 years ago on the Indian subcontinent and was probably later taken up in Europe, during Alexander the Great’s military campaigns in the fourth century. Herpes is usually spread from parent to child through close contact. Romantic kissing might have provided HSV-1 with a faster route to infect people and could have helped the virus outcompete earlier versions of herpes, the researchers say.

Fully unraveling the history of herpes and other pathogens will require older and more geographically diverse samples, but this study is a good example of the kind of information that can be accessed with ancient DNA, says Daniel Blanco-Melo, an evolutionary virologist at the University of Washington in Seattle.

Theoretically, researchers could sequence DNA from pathogens that infected even older humans and animals, potentially living one million years ago, Sikora says. This might allow scientists to learn about the organisms that infected ancient human species, such as Neanderthals and Denisovans. But technological limitations mean that researchers are currently able to sequence only the genetic material of pathogens that contain double-stranded DNA, excluding many important RNA viruses such as the ones that cause polio and measles.

Still, ancient DNA is providing a window into our shared history with disease, Sikora says. “We’re at the beginning of the maturation of this field,” he adds. “I expect we’re going to get very exciting new insights in the next couple of years.”

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