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

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

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

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

Enard’s group consulted a publicly available DNA database of 2,504 individuals from 26 ethnic populations on five continents, including Chinese Dai, Vietnamese Kinh and African Yoruba people. The team first focused on 420 proteins known to interact with coronaviruses, including 332 that interact with SARS-CoV-2, the virus that causes COVID-19. These interactions could range from boosting immune responses to making it easier for a virus to hijack a cell.

Substantially increased production of all 420 proteins, a sign of past exposures to coronavirus-like epidemics, appeared only in East Asians. Enard’s group traced the viral responses of 42 of those proteins back to roughly 25,000 years ago.

An analysis of the genes known to orchestrate production of those proteins determined that specific variants became more common around 25,000 years ago before leveling off in frequency by around 5,000 years ago. That pattern is consistent with an initially vigorous genetic response to a virus that waned over time, either as East Asians adapted to the virus or as the virus lost its ability to cause disease, Enard said. Twenty-one of the 42 gene variants act either to enhance or deter the effects of a wide array of viruses, not just coronaviruses, suggesting that an unknown virus that happened to exploit similar proteins as coronaviruses could have instigated 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.

It’s possible that DNA adjustments to coronavirus epidemics over many thousands of years may contribute to lower COVID-19 infection and death rates reported in East Asian nations, versus European countries and the United States, Quintana-Murci speculates. But it’s unknown at this point what, if any, effect those DNA tweaks could have. Many factors, including jobs that can’t be done remotely and lack of health care access, drive COVID-19 infections, he says (SN: 11/11/20; SN 7/2/20). And social factors, such as quick, strict lockdowns and widespread mask wearing, may have deterred infections in some East Asian nations.

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

Enard’s findings follow related evidence that a set of inherited Neandertal gene variants raise 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).