Over 20,000 Years Ago, a Coronavirus Epidemic Left Marks in Human DNA

The oldest modern coronavirus is about 820 years old, but humanity has been fighting similar viruses for millennia

Transmission electron microscopic image of the SARS-CoV-2 coronavirus
This transmission electron microscopic image shows the pandemic coronavirus SARS-CoV-2. CDC/ Cynthia S. Goldsmith and A. Tamin

A crown of spike-shaped proteins make coronaviruses recognizable when viewed under a microscope. But modern genetic analysis offers another way to find evidence of coronaviruses: detecting the marks the virus leaves behind in the populations it infects.

In a study published on June 24 in the journal Current Biology, researchers analyzed the DNA of thousands of people from around the world from 26 populations to look for signs of ancient coronavirus epidemics. The researchers found that people living in China, Japan and Vietnam faced a coronavirus for about 20,000 years in an epidemic that ended 5,000 years ago, Gemma Conroy and Anna Salleh report for ABC Science.

"There have always been viruses infecting human populations," said University of Arizona evolutionary biologist David Enard, who led the study, to Live Science’s Yasemin Saplakoglu in April, when the study was first published as a preprint. "Viruses are really one of the main drivers of natural selection in human genomes."

When coronaviruses infect humans, they rely on the microscopic machinery made by human genes in order to make more virus particles. So the research team focused on a few hundred human genes that interact with coronaviruses—but not other microbes—during an infection, reports Carl Zimmer for the New York Times.

In five groups of people, 42 of those genes had enough mutations to suggest they had evolved because of an epidemic. The genes may have become better at fighting off the viral infection, or less hospitable for the virus to use to copy itself. People with those mutations would have been more likely to survive an outbreak of the disease, and later, have children with the same genetic mutations.

“So what happens over several generations is the gene variants that are beneficial will rise in frequency," says University of Adelaid bioinformatics specialist Yassine Souilmi, a co-author of the study, to ABC Science. "And that leaves a very distinctive mark several generations later.”

It takes at least 500 to 1,000 years for that mark to become a noticeable, shared trait of a population, per ABC Science. But thousands of years ago, people only had infection-avoiding behaviors and their genes to protect them.

To determine how long ago the trait emerged, the researchers looked for random mutations within the 42 genes that they identified. The longer the trait had been around, the more random mutations happen. Because all 42 genes tended to have the same number of mutations, they probably became common in the population at the same time.

“This is a signal we should absolutely not expect by chance,” says Enard to the New York Times. So the researchers estimate that the coronavirus-fighting traits became common between 20,000 and 25,000 years ago.

"Viruses exert some of the strongest selective pressures on humans to adapt, and coronaviruses have presumably been around for a long time before humans existed," says University of California, San Diego systems biologist Joel Wertheim, who was not involved in the study, to Live Science. "So although it is not unexpected that coronaviruses would have driven adaptation in humans, this study presents a fascinating investigation into how and when this played out."

Modern medical interventions, like vaccines, mean the current coronavirus pandemic is unlikely to make a lasting mark on the human genome. And today, social factors have a greater impact on a person’s risk from a coronavirus infection than genetic factors.

"Things like the job a person does, existing health problems, and socioeconomic disadvantage are more likely to have an effect an individual's risk of disease," says Vicki Jackson, a statistical geneticist at the Walter and Eliza Hall Institute of Medical Research who was not involved in the study, to ABC Science.

However, Jackson adds the findings may inform research into treatments for Covid-19 and other coronavirus diseases, because the 42 genes once protected people from coronaviruses.

Souilmi says to the New York Times, “It’s actually pointing us to molecular knobs to adjust the immune response to the virus.”

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