February 25, 2024

Researchers have found evidence that a coronavirus epidemic swept East Asia about 20,000 years ago and was devastating enough to leave an evolutionary imprint on the DNA of people living today.

The new study suggests that the region was plagued by an ancient coronavirus for many years, researchers say. The finding could have devastating effects on the Covid-19 pandemic if it is not brought under control soon with vaccinations.

“It should worry us,” said David Enard, an evolutionary biologist at the University of Arizona who led the study, which was published Thursday in the journal Current Biology. “What is happening now could last for generations.”

So far, researchers have not been able to look very far back into the history of this family of pathogens. Over the past 20 years, three coronaviruses have adapted to infect people and cause serious respiratory illnesses: Covid-19, SARS, and MERS. Studies on each of these coronaviruses suggest that they jumped into our species from bats or other mammals.

Four other coronaviruses can also infect people, but usually only cause mild colds. Scientists didn’t directly observe how these coronaviruses became human pathogens, so they relied on indirect clues to gauge when the jumps happened. Coronaviruses acquire new mutations at roughly regular rates, and so by comparing their genetic variation it can be determined when they deviated from a common ancestor.

The youngest of these mild coronaviruses, called HCoV-HKU1, crossed species boundary in the 1950s. The oldest, called HCoV-NL63, can be up to 820 years old.

But before that, the coronavirus trail got cold – until Dr. Enard and his colleagues applied a new method to the search. Instead of looking at the coronavirus genes, the researchers looked at the effects on the DNA of their human hosts.

Viruses cause enormous changes in the human genome over generations. A mutation that protects against a viral infection can make the difference between life and death and is passed on to the offspring. For example, a life-saving mutation could allow humans to hack up the proteins of a virus.

But viruses can also develop. Your proteins can change shape to overcome a host’s defenses. And these changes could spur the host to develop even more counter-offensives, which leads to more mutations.

If a random new mutation creates resistance to a virus, it can quickly become more common from one generation to the next. And other versions of this gene are becoming rarer. So if, in large groups of people, one version of a gene dominates all the others, scientists know that it is most likely a sign of rapid evolution in the past.

In recent years, Dr. Enard and his colleagues searched the human genome for these genetic variation patterns to reconstruct the history of a number of viruses. When the pandemic broke out, he wondered if ancient coronaviruses had left their own mark.

He and his colleagues compared the DNA of thousands of people from 26 different populations around the world and examined a combination of genes known to be crucial for coronaviruses but not other types of pathogens. In East Asian populations, the scientists found that 42 of these genes had a dominant version. That was a strong signal that people in East Asia had adapted to an ancient coronavirus.

But whatever happened in East Asia seemed to be confined to that region. “When we compared them to populations around the world, we couldn’t find the signal,” said Yassine Souilmi, postdoctoral fellow at the University of Adelaide in Australia and co-author of the new study.

The scientists then tried to estimate how long East Asians had already adapted to a coronavirus. They took advantage of the fact that once a dominant version of a gene begins to be passed down through the generations, it can acquire harmless random mutations. The more time goes by, the more of these mutations accumulate.

Dr. Enard and his colleagues found that all 42 genes had about the same number of mutations. That meant they had all evolved rapidly at about the same time. “This is a signal that we should definitely not expect by chance,” said Dr. Enard.

They estimated that all of these genes developed their antiviral mutations sometime between 20,000 and 25,000 years ago, most likely over the course of a few centuries. This is a surprising finding, since the East Asians did not live in dense communities at the time, but rather formed small groups of hunters and gatherers.

Aida Andres, an evolutionary geneticist at University College London who was not involved in the new study, said she found the work compelling. “I’m pretty sure there is something,” she said.

Still, she didn’t think it was possible to give an accurate estimate of how long ago the ancient epidemic was. “Timing is a complicated thing,” she said. “Whether that happened a few thousand years before or after – I personally think we can’t be so sure about it.”

Scientists looking for drugs to fight the new coronavirus may want to study the 42 genes that evolved in response to the old epidemic, said Dr. Souilmi. “It actually points us to molecular buttons to adjust the immune response to the virus,” he said.

Dr. Anders agreed, saying that the genes identified in the new study should receive special attention as drug targets. “You know they are important,” she said. “That’s the beauty of evolution.”