According to a new study, a Neanderthals transmitted a stretch of DNA linked to Covid-19 60,000 years ago.
Scientists do not yet know why this particular segment increases the risk of severe coronavirus disease. But the new findings, which were published online Friday and have yet to be published in a scientific journal, show how some clues to modern health stem from ancient history.
“This crossover effect that occurred 60,000 years ago is still having an impact today,” said Joshua Akey, a geneticist at Princeton University who was not involved in the new study.
This study found that this part of the genome, spanning six genes on chromosome 3, has had a perplexing journey through human history. The variant is now common in Bangladesh, where 63% of people carry at least one copy. Across South Asia, almost a third of people have inherited the segment.
Elsewhere, however, the segment is much less common. Only 8% of Europeans wear it, and only 4% have it in East Asia. It is almost completely absent in Africa.
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It is unclear what evolutionary pattern produced this distribution in the past 60,000 years. “That’s the $ 10,000 question,” said Hugo Zeberg, a geneticist at the Karolinska Institute in Sweden, one of the authors of the new study.
One possibility is that the Neanderthal version is harmful and has become increasingly rare overall. It is also possible that the segment improved people’s health in South Asia, perhaps by providing a strong immune response to viruses in the region.
“One must emphasize that at this point this is pure speculation,” said Zeberg’s co-author Svante Paabo, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
Researchers are just beginning to understand why Covid-19 is more dangerous to some people than to others. Older people are more likely to become seriously ill than younger people. Men are more at risk than women.
Social inequality is also important. In the United States, black people are much more likely than white people to become seriously ill with the coronavirus, for example, probably due in part to the country’s history of systemic racism. It has left black people with a high rate of chronic diseases like diabetes, as well as living and working conditions that can increase exposure to the virus.
Genes also play a role. Last month, researchers compared people in Italy and Spain who became seriously ill with Covid-19 with those who only had mild infections. They found two places in the genome associated with increased risk. One is on chromosome 9 and includes ABO, a gene that determines blood type. The other is the Neanderthal segment on chromosome 3.
But these genetic findings are rapidly updating as more people infected with the coronavirus are studied. Last week, an international group of scientists called the Covid-19 Host Genetics Initiative released a new dataset that minimizes the risk of blood type. “The jury is still in ABO,” said Mark Daly, a geneticist at Harvard Medical School, a member of the initiative.
The new data showed an even stronger link between the disease and the chromosome 3 segment. People who carry two copies of the variant are three times more likely to get serious diseases than people who don’t.
After the new batch of data came out on Monday, Zeberg decided to find out if the chromosome 3 segment was transmitted from Neanderthals.
About 60,000 years ago, some ancestors of modern humans expanded outside of Africa and spread across Europe, Asia, and Australia. These people encountered Neanderthals and mestizos. Once Neanderthal DNA entered our gene pool, it spread through the generations, long after the Neanderthals went extinct.
Most of the Neanderthal genes turned out to be harmful to modern humans. They may have been a burden on people’s health or made it difficult to have children. As a result, Neanderthal genes became rarer, and many disappeared from our gene pool.
But some genes seem to have provided an evolutionary advantage and have become quite common. In May, Zeberg, Paabo and Dr. Janet Kelso, also from the Max Planck Institute, discovered that a third of European women have a Neanderthal hormone receptor. It is associated with higher fertility and fewer miscarriages.
Zeberg knew that other Neanderthal genes that are common today even help us fight viruses. When modern humans expanded to Asia and Europe, they may have found new viruses against which Neanderthals had already developed defenses. We have clung to those genes ever since.
Zeberg observed chromosome 3 in an online database of Neanderthal genomes. He found that the version that increases the risk of severe Covid-19 is the same version found in a Neanderthal who lived in Croatia 50,000 years ago. “I texted Svante right away,” Zeberg said in an interview, referring to Paabo.
Paabo was on vacation in a cabin in the remote Swedish countryside. Zeberg showed up the next day, and they worked around the clock until they published the study online on Friday.
“It’s the craziest vacation I’ve ever had at this cabin,” said Paabo.
Tony Capra, a geneticist at Vanderbilt University who was not involved in the study, thought it was plausible that the Neanderthal DNA fragment originally provided a benefit, perhaps even against other viruses. “But that was 40,000 years ago, and here we are now,” he said.
It is possible that an immune response that worked against old viruses has ended up exaggerating against the new coronavirus. People who develop severe cases of Covid-19 generally do so because their immune systems launch uncontrolled attacks that end up scarring their lungs and causing inflammation.
Paabo said the DNA segment may partly explain why people of Bangladeshi descent are dying at a high rate of Covid-19 in the UK.
It is an open question whether this Neanderthal segment continues to maintain a strong link to Covid-19 as Zeberg and other researchers study more patients. And it can take findings from the segment on ancient fossils of modern humans to understand why it became so common in some places but not others.
But Zeberg said the 60,000-year journey of this piece of DNA in our species could help explain why it is so dangerous today.
“Its evolutionary history may give us some clues,” said Zeberg.
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