Neandertal gene variants both increase and decrease the risk for severe COVID-19 | Karolinska Institutet NyheterReaders may remember how, back last October, I reported on a paper from researchers at Karolinska Institutet and the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, which showed that a gene carried on chromosome 3, which we inherited from our Neanderthal cousins, is a significant risk factor for severe Covid-19.
Now the same team have shown that Neanderthals also contributed a protective variant, carried on chromosome 12, that helps us fight RNA viruses. Genes known as OAS, from this region of chromosome 12, code for protein enzymes that break down viral RNA. People with this Neanderthal variant have a 20% lower chance of needing intensive care in hospital if they become infected with the SARS-CoV-2 coronavirus. This allele is present in half the non-African population of the world, showing in conveys a significant benefit and so has been steadily increasing in the human gene pool.
This shows that our heritage from Neandertals is a double-edged sword when it comes to our response to SARS-CoV-2. They have given us variants that we can both curse and thank them for.
It is striking that this Neandertal gene variant has become so common in many parts of the world. This suggests that it has been favourable in the past. It is also striking that two genetic variants inherited from Neandertals influence COVID-19 outcomes in opposite directions. Their immune system obviously influences us in both positive and negative ways today.
Hugo Zeberg, co-author
Department of Neuroscience, Karolinska Institutet,
and the Max Planck Institute for Evolutionary Anthropology
Department of Neuroscience, Karolinska Institutet,
and the Max Planck Institute for Evolutionary Anthropology
It is striking that this Neandertal gene variant has become so common in many parts of the world. This suggests that it has been favourable in the past. It is also striking that two genetic variants inherited from Neandertals influence COVID-19 outcomes in opposite directions. Their immune system obviously influences us in both positive and negative ways today.
Svante Pääbo, coauthor.
Director at the Max Planck Institute for Evolutionary Anthropology.
Director at the Max Planck Institute for Evolutionary Anthropology.
This is as good an example as we could want of how evolution works. A beneficial allele is acquires, in this case by ingress following interbreeding between two related species, and environmental selection pressure, in this case viruses, causes the frequency of the allele to increase in the gene pool.Significance
We show that a haplotype on chromosome 12, which is associated with a ∼22% reduction in relative risk of becoming severely ill with COVID-19 when infected by SARS-CoV-2, is inherited from Neandertals. This haplotype is present at substantial frequencies in all regions of the world outside Africa. The genomic region where this haplotype occurs encodes proteins that are important during infections with RNA viruses.
Abstract
It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.
Zeberg, Hugo; Pääbo, Svante
A genomic region associated with protection against severe COVID-19 is inherited from Neandertals
Proceedings of the National Academy of Sciences March 2, 2021 118 (9) e2026309118; doi: 10.1073/pnas.2026309118
Copyright: © 2021 The authors. Published by PNAS
Open access
Reprinted by a Creative Commons Attribution License 4.0 (CC BY 4.0)
This is part of the process whereby the genes non-African people got from Neanderthals have been sorted by evolution to get rid of any seriously detrimental alleles and to retain and increase their numbers when they are beneficial.
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