Researchers from Karolinska University have discovered a gene that reduces the severity of Covid infections by 20%. In their paper the scientists state that this explains why the disease’s symptoms are so variable, hitting some harder than others.
Why do some people fall severely ill from COVID-19 while others don’t? In addition to risk factors like age or obesity and plenty of other environmental factors, it also comes down to our varying genetic makeup. Therefore, researchers across the globe have begun the mammoth task of mapping the genes involved in making people more susceptible to catching SARS-CoV-2 (COVID-19) and developing a severe infection.
These large-scale efforts have thrown up more than a dozen genomic regions along the human chromosome containing large clusters of genes associated with severe COVID-19. However, the specific causal genes in these regions are yet to be identified, hampering our ability to understand COVID-19’s often selective pathology.
Now, scientists build on these findings to pinpoint a gene that confers protection from critical illness.
Neanderthal DNA protects against severe COVID-19
The previous studies from 2020 concentrated on the genetic data of people of European ancestry recorded by multi-disciplinary teams all over the world for the 1000 Genomes Project. This monumental collaboration uncovered a specific segment of DNA known as the OAS1/2/3 cluster, which lowers the risk of developing an acute COVID-19 infection by 20%. Inherited from Neanderthals in roughly half of all people outside of Africa, this segment is responsible for encoding genes in the immune system.
The genetic array came about as a result of the migration of an archaic human species out of the African continent about 70,000 years ago who mated and mingled DNA with Neanderthals reproduced in their offspring’s haplotypes, a set of inheritable DNA variations close together along a chromosome.
However, most human haplotypes outside Africa now include DNA from Neanderthals and Denisovans (an ancient human originating in Asia). Consequently, this ancient region of DNA is heaving with numerous genetic variants, making it challenging to distinguish the exact protective gene that could serve as a target for medical treatment against severe COVID-19 infection.
A possible solution is that people of African descent do not contain these archaic genes in their haplotypes, making them shorter and easier to decipher.
To test this theory, the researchers checked the 1000 Genomes project database for individuals carrying only parts of this DNA segment – focusing on individuals with African ancestry who lack heritage from the Neanderthals. Remarkably, the researchers found that individuals of predominantly African ancestry had the same protective gene cluster as those of European origin.
Genetic studies should be a multi-cultural affair
Once they established this, the researchers collated 2,787 COVID-19 cases with the genetic data of 130,997 individuals of African ancestry to reveal the gene variant rs10774671 G thought to convey protection against COVID-19 hospitalization. Their results correspond to a previous, more extensive study of individuals of European heritage, with analysis suggesting it is likely the only causal variant behind the protective effect.
Surprisingly, this previously ‘useless’ ancient variant was found to be widespread, present in one out of every three people of white European ancestry and eight out of ten individuals of African descent.
In evolutionary terms, the researchers write that the variant exists today in both these gene pools “as a result of their inheritance from the ancestral population common to both modern humans and Neanderthals.” Accordingly, their data adds more weight to the standard held theory that a common ancestor originated in Africa millions of years ago before sharing their DNA across the globe.
And while there’s much more to uncover regarding the newly discovered variant, the researchers can firmly suggest at this stage that the protective gene variant (rs10774671 G) works by determining the length of a protein encoded by the gene OAS1. As the longer version of the protein is more effective at breaking down the virus than the unaltered form, a life-threatening infection is less likely to occur.
Using genetic risk factors to design new COVID-19 drugs
Despite their promising results, the team cautions that the 1000 Genomes Project does not provide a complete picture of this genomic region for different ancestries. Nevertheless, it’s clear that the Neanderthal haplotype is virtually absent among individuals of primarily African ancestry, adding, “How important it is to include individuals of different ancestries” in large-scale genetic studies.
Senior researcher Brent Richards from McGill University says that it is in this way “we are beginning to understand the genetic risk factors in detail is key to developing new drugs against COVID-19.”
If these results are anything to go by, we could be on the cusp of novel treatments that can harness the immune system to fight this disease.
