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A coronavirus epidemic may have reached East Asia about 25,000 years ago

An ancient coronavirus, or a closely related pathogen, caused an epidemic among the ancestors of present-day East Asians about 25,000 years ago, a new study indicates.

DNA analysis of more than 2,000 people shows that genetic changes in response to that persistent epidemic have accumulated over the next 20,000 years or so, David Enard, an evolutionary geneticist at the University of Arizona in Tucson, reported on April 8. the American Association of Physical Anthropologists. The discovery raises the possibility that some East Asians today inherited biological adaptations to coronaviruses or closely related viruses.

The discovery paves the way for exploring how genes linked to ancient viral epidemics may contribute to outbreaks of modern diseases, such as the COVID-19 pandemic. Genes with long-standing viral histories may also provide clues for researchers looking for better antiviral drugs, although that remains to be demonstrated.

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The Enard group consulted a publicly accessible DNA database of 2,504 individuals from 26 ethnic populations on five continents, including Chinese Dai, Vietnamese Kinh and African Yoruba. The team first focused on 420 proteins that are known to interact with coronaviruses, including 332 that interact with SARS-CoV-2, the virus that causes COVID-19. These interactions can range from increased immune responses to facilitating the sequestration of a cell by a virus.

The substantial increase in the production of the 420 proteins, a sign of past exposures to coronavirus-like epidemics, has only appeared in East Asians. The Enard group tracked the viral responses of 42 of those proteins until about 25,000 years ago.

An analysis of the genes that orchestrate the production of these proteins determined that specific variants became more common about 25,000 years ago before leveling in frequency about 5,000 years ago. That pattern is consistent with an initially vigorous genetic response to a virus that has diminished over time as East Asians have adapted to the virus or when the virus has lost its ability to cause disease, Enard said. Twenty-one of the 42 gene variants act to enhance or deter the effects of a wide variety of viruses, not just coronaviruses, suggesting that an unknown virus that exploded coronavirus-like proteins could have caused the ancient epidemic, Enard said.

These findings "show that East Asians have been exposed to coronavirus-like epidemics for a long time and are more (genetically) adapted to epidemics of these viruses," says evolutionary geneticist Lluis Quintana-Murci of the Pasteur Institute in Paris, who was not involved in the new study.

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It is possible that DNA adjustments to coronavirus epidemics over thousands of years may have contributed to lower reported COVID-19 infection and mortality rates in East Asian nations, compared to European countries and the United States, speculates Quintana-Murci . But at this point it is unknown what effect, if any, such DNA modifications might have. Many factors, including work that cannot be done remotely and lack of access to health care, cause COVID-19 infections, according to him (SN: 11/11/20; SN 7/2/20). And social factors, such as quick, strict blockages and widespread use of masks, can deter infections in some East Asian nations.

Large-scale genetic studies in modern East Asian and ancient human DNA probes spanning the last 25,000 years are needed to explore how the 42 gene variants identified may contribute to COVID-19 or other coronavirus infections. These variants may also present opportunities to develop COVID-19 treatments, Enard said. So far, only four of those genes are targets of 11 drugs that are used or investigated in COVID-19 treatment studies, he said.

Enard’s findings follow related evidence that a set of inherited Neanderthal genetic variants increases the risk of developing severe COVID-19 in some South Asians and Europeans, while others may provide some level of protection (SN: 10/2/20; SN: 2/17/21).

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