Genetic study reveals that humanity faced a coronavirus epidemic 20 thousand years ago

Researchers have found evidence that the epidemic was devastating enough to leave an evolutionary imprint on the DNA of people alive today. They used the largest public database of common human genetic variations

Since January 2020, the increasing proliferation of the new Coronavirus has become one of humanitys greatest challenges. In the last 20 years, three serious epidemics caused by viruses of the Coronaviridae family have been reported: severe acute respiratory syndrome (SARS), which appeared in China and killed more than 800 people worldwide between 2002 and 2003; Middle East Respiratory Syndrome (MERS), which erupted in Saudi Arabia in 2012 and killed more than 850 people; and SARS-CoV-2, which has killed more than 4 million people worldwide. In the relentless search for concrete information about the origin of the current pandemic, a study published in late June in the journal Current Biology entitled An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia revealed that this viral family is already known to mankind.

Scientists have studied the evolution of the human genome and identified remnants of a major coronavirus epidemic that erupted 20 years ago in East Asia, a region that includes China, Japan, Mongolia, North Korea, South Korea and Taiwan, and left a trail in the DNA of people from China, Japan and Vietnam. The researchers used data from the 1,000 Genomes Project, the most detailed catalog of human genetic variation ever created, and analyzed changes in genes encoding proteins that interact with the Sars-CoV-2. virus. Then, they synthesized both the proteins of this coronavirus and others that are common in humans and noticed that the samples showed signs of how the infectious agent invades human cells. And so they discovered that the ancient peoples of East Asia suffered from a disease caused by a virus similar to the one that causes COVID-19.

To carry out the study, the researchers applied computer analysis to the genomes of more than 2,500 people from 26 populations around the world and found signatures in 42 different human genes. These signs were present in only five populations, all from East Asia, the likely ancestral homeland of the coronavirus family. This suggests that the ancestors of modern East Asians were first exposed to coronaviruses about 20 thousand years ago.

University of Queensland biology professor and leader of the research that uncovered the ancestral epidemic, Dr. Kirill Alexandrov explains that all genomes constantly accumulate mutations, most are harmless and do not lead to any change in the function of the genes they affect. “We can look at the mutation rate as a genetic clock in a constant ticking. However, when there is selection pressure, the clocks of some genes start to run much faster as they accumulate advantageous mutations. This is due to the fact that people with useful mutations in their genes survive a pandemic better than individuals without such mutations. As a result, these adaptive mutations accumulate in the population. When comparing a very large number of sequenced human genomes it was shown that >20,000 of the clocks of many human genes that SARS-CoV2 is using to manipulate human cells started to work faster simultaneously, probably indicating that there was a viral pandemic caused by a similar virus”, details the professor.

Looking to the past for clues about the future

Unraveling the evolutionary history of past coronavirus outbreaks may offer clues about how to respond to future pandemics. Asked whether the findings can help fight the current pandemic, Dr. Alexandrov argues that the study shows genes that are likely to be essential for the viruss ability to invade and subvert human cells and that this information can be exploited for the development of antiviral therapies. He also recalls that the study indirectly emphasizes the importance of vaccination as the old pandemic lasted hundreds of years. Furthermore, by discovering the genes affected by historical viral outbreaks, the research points to the promise of evolutionary genetic analysis as a new tool to combat future crises. This allows us to compile a list of potentially dangerous viruses and then develop diagnoses, vaccines and medications in case they return. By obtaining information about ancient viral enemies, the scientific community advances in understanding how the human genome adapted to viruses and how it managed to convert them into allies of the evolutionary process.

Twenty thousand years ago, there was no medical knowledge, public health policy, vaccines, or coordinated global response to address an epidemic. So, how did humanity overcome the coronavirus? In the opinion of Dr. Alexandrov, probably, over hundreds of years of epidemic, the population of East Asia adapted to the disease and became milder and presumably resulted in a decrease in viral loads. This, perhaps, in combination with environmental factors led to a natural termination of the pandemic. That is, while the disease was spreading, an evolutionary natural selection ended up favoring human genes with favorable adaptive changes. Possibly, this caused the disease to affect the population less severely over time.

For Dr. Alexandrov, the relevance of this study lies in providing the methodology for analyzing severe pandemics, in addition to giving an insight into the impact of the current coronavirus pandemic on the population. “In addition, the study left us some important messages: in the past there have been large and long-lasting coronavirus pandemics that have led to a large number of deaths in the population; it is possible to identify and experimentally validate molecular mechanisms of old pandemics”, he emphasizes. By developing a better understanding of ancient viral enemies, the team also gained an understanding of how the genomes of different human populations adapted to the viruses and concluded that during the epidemic, natural selection favored genes that adapted to the disease, which probably led to less severe effects.

Asked if they found evidence that the virus involved in the old outbreak invaded cells in a similar way to SARS-CoV-2, the professor notes that both viruses used an overlapping set of genes and, therefore, are probably related. However, this is circumstantial evidence and not direct evidence. Understanding how the interaction between the virus and the host cell takes place is fundamental for the development of drugs against Covid-19, whether for prevention or treatment. To learn more about this, the researchers combed through human genes looking for mutations that could explain previous contacts between coronaviruses and individuals of our species.

Having this information before the pandemic could have taken some steps forward in providing better and more diagnostics, more first-line drugs, and perhaps some initial vaccine trials. This was an international, interdisciplinary, and interagency study that came to life in the first months of the pandemic. Experts from the Universities of Arizona and California, both in the United States, and the University of Adelaide, in Australia, contributed.