Some people’s genetic inheritance from Neandertals may raise their risk of developing severe COVID-19.
A stretch of DNA on human chromosome 3 was previously found to be associated with an increased risk of developing severe disease from coronavirus infection and of being hospitalized. Some genetic heirlooms passed down after humans interbred with Neandertals more than 50,000 years ago are known to affect immune system function and other aspects of human health even today. So researchers decided to see whether Neandertals and other extinct human cousins called Denisovans also share the risky region.
“I fell off my chair. It was really a surprise to see that the genetic variants were exactly the same as Neandertals’,” says evolutionary geneticist Hugo Zeberg of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and the Karolinska Institute in Stockholm. Zeberg and his Max Planck colleague Svante Pääbo report the findings September 30 in Nature.
About half of people whose ancestors hail from South Asia — particularly Bangladesh — and about 16 percent of people in Europe today carry this bit of Neandertal legacy, the new study finds.
The risky DNA was identified as a COVID-19 danger zone in genome-wide association studies, or GWAS, which use statistical methods to find genetic variants that show up more often in people with a particular disease than in those without the disease. In this case, the comparison was between people who have milder forms of COVID-19 and people who required hospitalization.
This stretch on chromosome 3 contains multiple genetic variants that are almost always inherited together, forming a block known as a haplotype. Those variants aren’t necessarily the genetic tweaks that lead to more severe disease, but they flag that one or more genes in the region might be responsible for increasing susceptibility to the coronavirus. The researchers are working to figure out which genes in the region might be contributing to susceptibility, Zeberg says.
Of 13 genetic variants that make up the risky haplotype, 11 were found in the DNA of a 50,000 year-old Neandertal from Vindija Cave in Croatia, and three were shared with two Neandertals from the Altai mountains in Russia. Denisovans, on the other hand, didn’t carry these variants.
Although most non-Africans carry some Neandertal DNA as a relic of ancient interbreeding, inheritance of the COVID-19 susceptibility haplotype was patchy. The haplotype didn’t get passed down in East Asia, but people of South Asian ancestry were more likely to carry the Neandertal legacy. About 63 percent of people in Bangladesh have at least one copy of the disease-associated haplotype, and 13 percent have two copies (one from their mother and one from their father). For them, the Neandertal DNA might be partially responsible for increased mortality from a coronavirus infection. People of Bangladeshi origin living in the United Kingdom, for instance, are twice as likely to die of COVID-19 as the general population.
That patchwork inheritance pattern may indicate that different evolutionary pressures were at work during the haplotype’s history, says Tony Capra, an evolutionary geneticist at the University of California, San Francisco. “It’s an important lesson about genetic variation; what’s good in one place can be bad in another place.”
In Bangladesh, the haplotype may have given people an evolutionary advantage in fighting off other pathogens, such as cholera, allowing it to increase in frequency, Zeberg speculates. In East Asia, it might have been an evolutionary disadvantage when dealing with other illnesses, leading to its decline.
The results don’t mean that carrying Neandertal DNA will cause people to become severely ill — nor that not having it will protect people. East Asians generally have more Neandertal DNA than other groups, but didn’t inherit this risky heirloom. Still, thousands of people in China and other parts of East Asia have died of COVID-19. On the other hand, people of African descent have little to no Neandertal DNA, but Black Americans are among those at highest risk of dying of COVID-19, often for reasons that may have nothing to do with their genes.
Capra stresses that “with COVID-19, there’s a genetic component that is important, but social and other environmental factors are so much more important in determining risk and severity.” For instance, one of the biggest risk factors is age, with young children at the least risk and elderly people far more likely to be hospitalized or die when they contract COVID-19.
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