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Left-Over Neanderthal DNA Affects Our Vulnerability To COVID-19

Biden recently called Texas “Neanderthal” (pronounced “ne-ander-TALL,” not “THall”) for doing away with pandemic restrictions. Texas did so because it has seen a sharp decline in COVID-19, and it just reported its first day with no COVID-19 deaths. Maybe Biden is right, who knows? But maybe Texan’s residual Neanderthal genes could explain its drop in infections and deaths.

Neanderthals evolved in Western Eurasia about half a million years ago and died out around 40,000 years ago, but they did leave a bit behind. In the past decade, sequencing of DNA extracted from fossils and other samples from ancient hominids have shown that Neanderthals and Homo sapiens co-existed, and even consorted, producing hybrid offspring. Almost half of the Neanderthal genome still survives, scattered among almost all modern people’s DNA. The exception is those with mostly Sub-Saharan African ancestors, since Neanderthals seem never to have lived in Africa.

Such ancient genes in modern humans have been associated with things like hairiness and fat metabolism. Some of the left over Neanderthal genes also are linked with how our system affects things like risk of lupus, Crohn's disease, allergies, and diabetes. A pair of recent papers now suggests that COVID-19 belongs on that list as well. Two long stretches of DNA we inherited from Neanderthals, appear to confer either resistance or susceptibility to severe COVID-19.

Researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig, where research on Neanderthal DNA was pioneered, published in the Journal Nature last September that one Neanderthal DNA string on human chromosome 3 provides the major genetic risk factor for serious COVID-19 illness (other non-genetic risk factors include co-morbid conditions such as age, being male, obesity, diabetes, etc.). Those who carry one copy of that archaic DNA sequence have a 2-fold risk of a trip to the ICU upon infection. Those who have two copies of that sequence, one from each parent, have another doubling of risk for serious disease. The distribution of that ancient sequence around the world is uneven, possibly explaining regional differences in the incidence of severe COVID-19. In Bangladesh, 63% of Bengalis carry at least one copy, whereas it is found in only about 16% of Europeans. Not surprisingly, it is almost absent in Africa, and more surprisingly, rare in large areas of Eastern Asia. One can only speculate that it also might be rare in Texans.

How the gene affects COVID-19 severity is not known, but one gene within the sequence encodes a protein that interacts with the cell receptors used by the CoV-2 virus to enter cells. The sequence is also thought to affect cytokine production. An over-exuberant cytokine “storm” response to infection is one way that COVID-19 leads to severe disease. It is interesting that such a cytokine response is protective against cholera and that cholera has long been a problem in Bangladesh and India. That could explain why this specific Neanderthal DNA sequence has been fixed at a high frequency in the genomes of those populations—it confers a survival advantage to an endemic infectious disease. This is reminiscent of why the sickle cell genetic trait is prevalent in Sub-Saharan Africa. That genetic trait protects carriers against malaria, so it confers a survival advantage to people living in areas endemic with malaria.

The second study, published by the same lab in February in the Proceedings of the National Academy of Sciences links another Neanderthal DNA sequence found on human chromosome 12 to protection from serious disease. Carriers of this sequence are 22% less likely to develop serious disease. About 25-35% of the population in Eurasia carries at least one copy of the sequence, while about 50% in Vietnam and Eastern China do. Even before this area of chromosome 12 was discovered to come from Neanderthals, a gene in the area was known to hinder spread of RNA viruses like CoV-1 (SARS), West Nile virus, hepatitis C, and perhaps CoV-2. It instructs cells to commit suicide when they are infected by one of these viruses, hence reducing the viral load the infected cell can pump out.

All of this provides genetic clues on why some countries and populations have been hit harder by COVID-19 than others, and why others do better.

So, just how Neanderthal are Texans? Do they have more of the good gene or just less of the bad gene? Alternatively, it might just be the chili—eat a bowl of Texas red and go maskless…..

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