Covid and Neanderthal genes
"Neanderthal" genes can both reduce and increase the risk of severe COVID-19
"How bizarrely the deck is shuffled," we can say in the words of Woland, looking at our nose, inherited from my grandmother, or the red hair of my paternal great–grandfather. However, our personal family tree did not "grow" for tens or even hundreds of years: among the ancestors of our contemporaries there are also Neanderthals who left the historical scene tens of thousands of years ago. This genetic "inheritance" still affects our appearance and health today, including resistance to diseases, including COVID-19. Although with this infection, as it turned out recently, everything is not as clear as previously thought.
The article by Hugo Zeberg and Svante Pääbo A genomic region associated with protection against severe COVID-19 is inherited from Neandertals is published in PNAS.
Neanderthals came to Western Eurasia about half a million years ago and for a long time lived almost isolated from the African ancestors of modern humans. These primitive people died out about 40 thousand years ago, leaving us their genetic "inheritance": the share of Neanderthal genes in the genome of modern humans is on average about 2%. For hundreds of thousands of years that Neanderthals have lived outside Africa, they have adapted to local infectious diseases, and several genetic variants they introduced into the genome of modern humans are associated with the work of immunity. For example, these are Neanderthal variants of toll-like receptors that reduce susceptibility to gastrointestinal infections caused by the bacterium Helicobacter pylori and the risk of allergies.
As you know, some people are seriously ill when infected with SARS-CoV-2, others are easily or completely asymptomatic. In addition to risk factors such as old age, obesity or diabetes mellitus, the development of severe COVID-19 is also associated with certain gene variants. For example, back in 2020, it was shown that the risk of respiratory failure and even death with a new coronavirus infection is significantly higher in people who have a cluster (haplotype) of six specific variants of different genes inherited jointly on the 3rd chromosome.
Recently, a study by the Consortium for Genetic Research identified seven more genetic loci that affect the course of COVID-19, located on the 6th, 12th, 19th and 21st chromosomes.
Researchers from the Karolinska Institute (Sweden) and the Max Planck Society Institute for Evolutionary Anthropology (Germany) the genomes of modern humans, including representatives of the Yoruba African people who do not have Neanderthal ancestors, as well as the well-known genomes of Neanderthals and Denisovans, were analyzed. As a result, it turned out that the haplotype on the 12th chromosome, associated with a low risk of severe coronavirus infection, also has a Neanderthal origin.
It is known that this region of the genome encodes proteins – the enzymes oligoadenylate synthetase OAS1, OAS2 and OAS3, which inhibit protein synthesis in virus-infected cells, preventing its reproduction. And the Neanderthal variant of OAS obviously works more efficiently: the presence of one copy of this haplotype in the genome reduces the risk of needing intensive therapy for COVID-19 by 22%.
Since genomic "dossiers" on thousands of ancient people have been collected in recent years, it is possible to directly assess the change in the frequency of occurrence of certain genetic variants over time. Applying this approach to Neanderthal haplotypes affecting the course of COVID-19, scientists found out that there is no "harmful" variant located on the 3rd chromosome in 16 studied genomes aged 40-20 thousand years, but it occurs in 10% of people who lived 20-10 thousand years ago. In modern humanity, it occurs with a frequency of about 12.5%, primarily in South Asia and Europe, but is practically absent in East Asia.
As for the "useful" variant, it was found in less than 10% of individuals who lived 40-20 thousand years ago, but since then its frequency in the human population has increased. Almost completely absent in sub-Saharan African populations, it is quite common (25-30%) among the population of most Eurasian populations, and less common on the American continent. So in general, we can say that Neanderthal genes more often protect against the severe course of coronavirus infection than contribute to its development.
By the way, several single mutations in this region of the 12th chromosome have already been studied in connection with other infections caused by RNA-containing viruses. It turned out that they provide increased resistance to diseases such as West Nile fever and hepatitis C. There is also evidence that one of the Neanderthal gene polymorphisms contributes to protection against the SARS-CoV coronavirus, which caused the SARS epidemic in 2003.
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