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Hugo Zeberg on Neanderthal genes and COVID-19

Read the full transcript of our Science Focus Podcast interview with Hugo Zeberg – listen to the full episode at the bottom of the page.

Jason Goodyer: How much of the human genome actually does has been inherited from Neanderthals?

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Hugo Zeberg: So everyone with roots outside Africa carries roughly two percent of Neanderthal DNA. But if we put all these pieces together, we find more than half of the Neanderthal genome in modern day humans. But it will differ between people. Some will carry some pieces, some will carry other pieces.

JG: Do people from certain areas carry more than others?

HZ: Indeed. So people in Africa never met Neanderthals. Neanderthals were a group of hominins that lived in Europe and Asia before modern humans entered this part of the world. So it’s really just people outside Africa.

JG: So how how do we know that we we’ve inherited Neanderthal DNA?

HZ: So during the last two decades, people have been working, studied this, and their draft genome was published 10 years ago. Svante Paabo 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.

JG: So it’s been done several times?

HZ: We have three really good genomes from one Neanderthal living in Croatia and two living in Siberia.

JG: Can we be confident that these were typical Neanderthals with typical Neanderthal DNA?

HZ: We, of course, have an issue with sampling with just three genomes. In general, they look strikingly different but for this particular gene that we’re discussing today, they actually does not look so different.

JG: Okay, so how did humans come to inherit this Neanderthal DNA in modern humans?

HZ: When modern humans entered Eurasia they met and interbred with Neanderthals and created offspring together. That occurred some 50 to 60 thousand years ago.

JG: So do we know if this interbreeding between the two was a common thing or was it quite rare?

HZ: More and more data suggests that it was prevalent. During the course of the evolution of the species, people have interbred everywhere whenever they met new people.

JG: So if we’re talking 50, 60 thousand years ago, that’s quite a quite a long time. It’s a fair amount of time for different genes to evolve it or to be picked up. Why did these Neanderthal genes persist for so long? Why do we still have them?

HZ: So, part of the genome is missing. And we believe that some variants were really detrimental early on. But one should say that this is an extra source of genetic variation and some are probably there because they were beneficial in a way.

We did a study earlier this year where a gene variant from Neanderthals actually decreased the risk of miscarriage and bleeding during early pregnancy. So we got probably some good variants or some negative variants.

JG: Right. So this isn’t the first time that specific functions of inherited Neanderthal genes have been identified now.

HZ: No, there was a handful of associations that are kind of very well studied. And there are more that we believe we will find.

JG: Okay. So let’s talk a bit more about your specific specific study now. So how exactly did you go about finding this fact?

HZ: So, there’s been a large collaborative international effort led from Helsinki, Finland, where scientists and clinicians have genotyped individuals with severe COVID, people that end up in the hospital or in the ICU or even die from the disease. And 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?’. And I fell off my chair. It was really a surprise. I just had the two datasets at hand at my computer and when comparing the biggest risk factor I saw immediately that it was a Neanderthal sequence. It was really striking.

JG: So, what specific functions do the genes that you’ve identified play in in the human body?

HZ: So, 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.

JG: You mentioned that the risk is bigger in carriers of these genes. How big actually is the effect?

HZ: So initially we saw it was about 60 per cent increase per copy. You can as I said, you can have one chromosome from your mother and one from your father. Latest data has actually increased a little bit higher. So that almost twice the risk.

If you carry one genetic variant for being a genetic effect, this is quite large. Most genetic variants, they slightly influence things. And this is, for being genetic, quite a large risk factor.

JG: Have we been able to identify the prevalence of specific symptoms in the carriers of these genes?

HZ: We should say is not Neanderthal genes, but Neanderthal gene variants. It’s not new genes from Neanderthals. But rather genetic variants. And we see that carrying these genetic variants is much more common in people that end up in hospital and end up at the ICU.

So does that have a bad progression of COVID-19. One study also saw an increase then in need of mechanical ventilation. So we don’t believe it has so much to do with susceptibility or the likelihood of actually attracting the virus, but rather how our bodies respond to it.

JG: Do we have any idea as to why this is the case?

HZ: So it might be these immune receptors. And we know that people that 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 so that the body responds to aggressively against the virus.

JG: So are there any sort of precedents to this sort of thing where genes such as these have been studied in immune responses to other diseases that might be able to steer as in in a certain direction with this research in the future?

HZ: So in total, Neanderthals, mostly in what has been studied before, mostly it seems to be a good variant. So it’s definitely not so surprising to see this kind of key mediators of the immune response emerging.

JG: OK, so now that we’ve we’ve got this knowledge about these genes, what can we do with it? Is it possible that this could help us find a treatment? Could it help us identify those more risk or we could expedient certain patients’ treatment thanks to having this knowledge?

HZ: Yes, indeed. So the fact that this 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. And as you point out, it could be. It could be. We and many others are trying to understand these genetic variants and to see which one of the genes in this region is important.

And some of these receptors are actually what we we say “druggable”. So that could point towards future treatment for COVID-19. And also, as as equating what you said, the risk stratification to identify people at risk might also be very important in and dealing with this disease.


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