Dr Hugo Zeberg, assistant professor in the department of neuroscience at the Karolinska Institute in Stockholm, Sweden, talks to Jason Goodyer about his research into Neanderthal genes and the impact they could have on COVID-19 patients.
How much of the human genome has been inherited from Neanderthals?
If you have roots from outside of Africa, then roughly 2 per cent of your DNA is Neanderthal. But if we put all these pieces together, we find more than half of the Neanderthal genome in modern humans. But it will differ between people: some carry some pieces, some carry other pieces.
How do we know that modern humans inherited Neanderthal DNA?
During the last two decades people have been studying this, and a draft Neanderthal genome was published 10 years ago. Svante Pääbo and his colleagues at the Max Planck Institute in Leipzig, with whom I collaborate, managed to extract the whole DNA code from Neanderthal bones that we can compare to people living today.
We have three really good Neanderthal genomes: one from a Neanderthal found in Croatia, and two found in Siberia.
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How did modern humans come to inherit this Neanderthal DNA?
When modern humans entered Eurasia, they met and interbred with Neanderthals and created offspring together. That occurred some 50,000 to 60,000 years ago. More and more data suggests that this interbreeding was prevalent.
During the course of the evolution of the species, people have interbred everywhere, whenever they met new people.
Why have these Neanderthal genes persisted in modern humans for so long?
Part of the Neanderthal genome is missing, but we believe that some variants were really detrimental early on. But some are probably there because they were beneficial in a way.
We did a study earlier this year and found that a gene variant from Neanderthals actually decreased the risk of miscarriage and bleeding during early pregnancy. So we probably got some good variants and some negative variants.
Tell us about your study.
There’s been a large collaborative international effort led from Helsinki, Finland, where scientists and clinicians have genotyped individuals with severe COVID – those people who have ended up in hospital or in the ICU or have even died from the disease.
I’ve played a small part in this consortium, but I also work with the Neanderthal genome so I thought, ‘Why not have a look?’ When I did, I fell off my chair. It was really a surprise. When comparing the biggest risk factor [of severe COVID], I saw immediately that it was a Neanderthal sequence. It was really striking.
How much does the Neanderthal gene variant affect the risk?
Initially we saw it was about a 60 per cent increase in risk per copy of the variant. You get one copy from your mother and one from your father. The latest estimate has actually increased a little bit higher to almost twice the risk if you carry one genetic variant. For a genetic effect, this is quite large. Most genetic variants only slightly influence things.
What specific functions do these neanderthal genes that you’ve identified play in the human body?
This region contains several immune receptors that are involved in the immune response. So that’s very intriguing and interesting. There is also a gene that forms a complex with the receptor for the virus, which is also of high interest, of course.
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Do we have any idea why people with these Neanderthal genes are affected badly by COVID-19?
It might be the immune receptors. And we know that people who get very sick with COVID-19 seem to have this ‘cytokine storm’ – some overreaction of the immune system. So this might be part of that, with the body responding too aggressively against the virus.
Have we been able to identify the prevalence of specific COVID symptoms in the carriers of these genes?
We see that carrying these genetic variants is much more common in people who end up in hospital and at the ICU, so in those who have a bad progression of COVID-19.
One study also saw an increase in need of mechanical ventilation [in these patients]. We don’t believe it has so much to do with susceptibility or the likelihood of actually contracting the virus, but rather how our bodies respond to it.
Is it possible that this could help us find a treatment, or help us identify those people who are more risk?
The fact that these genetic variants are from Neanderthals is perhaps more of an academic interest. But, of course, identifying the genes is important for understanding the disease.
We, and many others, are trying to understand these genetic variants to see which of the genes in this region is important. So that could point towards future treatment for COVID-19, and it could also help to identify people at risk and might also be very important in dealing with this disease.