From common ancestors

The gene variant that protects a person from the "severe" COVID-19 is half a million years old

"First-hand Science" based on ScienceAlert: Scientists Identify Specific Gene Variant That Protects Against Severe COVID-19

To date, scientists have already managed to identify several areas of our genome associated with both good protection against COVID-19 and, conversely, with the severe course of this disease. The difficulty is that it is still problematic to link these data with the work of specific genes. And recently, an international group of researchers managed to identify a "protective" gene variant common to people of different origins.

One of the risk factors for the development of a severe form of COVID-19, along with old age, overweight and diabetes mellitus, are the genetic characteristics of a person. Back in 2020, a genetic combination (haplotype) was established on the 12th chromosome, the carriers of which have a reduced risk of severe coronavirus infection: for them, the probability of intensive therapy is reduced by almost a quarter.

This region contains genes encoding proteins-enzymes of oligoadenylate synthetase OAS1-3, which are involved in the innate immune response to viral infections. Scientists found out this by analyzing the genetic data of people of predominantly European origin and concluded that modern man received this "protective" haplotype from Neanderthals. But all attempts to understand what exactly in the "Neanderthal site" DNA gives protection from COVID-19 have yielded mixed results.

In particular, one of the variants of the oas1 gene (labeled as rs10774671) with an interesting feature also got into the candidates.

As is known, an RNA molecule read from any gene, before becoming a matrix for protein synthesis, undergoes splicing – a kind of "maturation", during which certain nucleotide sequences are cut out of it. The candidate variant defines an alternative splicing of immature RNA, in which smaller "pieces" are cut out of it. As a result, the synthesized protein-enzyme OAS1 turns out to be longer and about 60% more active than the "standard" one. However, it was not possible to prove that this particular variant of several hundred candidate DNA sequences is associated with the severity of COVID-19.

Now scientists have studied the DNA site where the genes encoding the OAS proteins are located in people of African descent – as is known, most of them do not have the genes of Neanderthals and Denisovans. Therefore, the corresponding section of their genome is shorter.

Scientists analyzed all available genetic information from 6 different studies, where the severity of COVID-19 was assessed (a total of 2,787 cases) people of African descent, as well as more than 130 thousand "control" genomes of Africans. As a result, they identified the same gene variant rs10774671 in them and found that in this group it reduces the risk of severe COVID-19.

Since this genetic "protection" is available to both Africans and Europeans, it begs the conclusion that such a useful gene variant in the current situation is inherited by modern people from a common ancient ancestral population, and it itself arose about half a million years ago.

If this protective effect is actually associated with an increase in the activity of the enzyme OAS1, then this can be used in the development of new therapies.

Article by Huffman et al. Multi-ancestry fine mapping implies OAS1 splicing in risk of severe COVID-19 is published in the journal Nature Genetics.

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