Instant Genius - Hugo Zeberg: How could Neanderthal genes affect COVID-19?

Episode Date: October 12, 2020

In this week's episode of the Science Focus Podcast, we talk to Hugo Zeberg, a geneticist working at the Karolinska Institute in Stockholm.  Hugo has just published a paper that suggests those of us with a certain set of genes inherited from Neanderthals may suffer from more severe effects of COVID-19. Let us know what you think of the episode with a review or a comment wherever you listen to your podcasts. Subscribe to the Science Focus Podcast on these services: Acast, iTunes, Stitcher, RSS, Overcast Read the full transcription [this will open in a new window] This podcast was supported by brilliant.org, helping people build quantitative skills in maths, science, and computer science with fun and challenging interactive explorations. Listen to more episodes of the Science Focus Podcast: Dr Rachel Brown: Why are some COVID-19 patients suffering from neurological complications? Project Discovery: Could computer games help find a cure for COVID-19? Elisa Raffaella Ferrè: What happens to the brain in space? Sandro Galea: What is the difference between health and medicine? Nessa Carey: Is gene editing inspiring or terrifying? Dean Burnett: What’s going on in the teenage brain? Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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available in print and in several digital formats throughout the world. Find out more at sciencefocus.com or look out for us in your app store. Hello and welcome to the Science Focus podcast. I'm Jason Goodyear, commissioning editor at BBC Science Focus magazine. In this week's episode, I'm talking to Hugo Zberg, a geneticist working at the Karolinska Institute in Stockholm. He's just published a paper that suggests those of us with a certain set of genes inherited from Neanderthals may suffer from more severe effects of COVID-19 if we catch it.

Thanks for taking the time to talk to us, Hugo. Oh, I'm glad to be here. Thank you. That's great. So first off, I guess the first question I would ask is how much of the human genome actually does, has been inherited from Neander? So everyone with roots outside Africa carry roughly 2% of Neanderthal DNA. But if we put all these pieces together, we find more than half of the Neanderthal genome in modern-day humans, in people living today. But it would differ between some will carry some pieces, some would carry other pieces.

So is it people from certain areas? carry more than others? Indeed. So as I started, people in Africa, they never met Neanderthals. Neanderthals were a group of hominists that lived in Europe and Asia before the modern humans enter this part of the world. So it's really people outside Africa. Okay. So how do we know this, that we've inherited Neanderthal DNA? So during the last two decades, people have been working to study this. And the draft genome was published 10 years ago, the draft genome of a Neanderthal. And Svante Pabwe and his colleagues at the Max Planck Institute in Leipzig, with whom I'm

collaborate and also work with, they managed to extract the whole DNA code from bones. And then we can compare. can compare it to people living today. So is that being done just the once, or has that been done several times? So we have three really good genomes, from one Neanderthal living in Croatia, to living that was found in Siberia. Okay, so we can be fairly confident that these were typical Neanderthals with typical Leanderthal DNA?

Yes, I mean, we of course have an issue. with sampling, with just three genomes. But they look, in general, they look striking different. But for this particular gene, what we're discussing today, they actually does not look so similar. Okay. So how did humans come to inherit this Neanderthal DNA, well, modern humans? So when modern humans entered Eurasia, they met probably early,

and then they interbred with Neanderthals and got offspring together. And that occurred some 50 to 60,000 years ago. So do we know if this interbreeding between the two was a common thing or was it quite rare? More and more data suggests that there are multiple events. and during the course of evolution of species, people have interbred everywhere when they met new people. Okay, so it's likely it was a pretty common event. Yes, but since we share so similar amount of 2% almost everyone,

except people in Africa, it probably occurred quite early. So if we're talking 50,000, 60,000 years ago, that's quite a long time. there's a fair amount of time for different genes to evolve or to be picked up. Why did these Neanderthal genes persist for so long? Why do we still have them? So parts 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 genetic variation, and some are probably there because they were. were beneficial in a way. So we did a study earlier this year where it was a gene variant from Neanderthals that actually decreased the risk of miscarriage and bleeds during early pregnancy. So we got probably some good variants and some negative variants. Right. So this isn't the first time that specific functions of inherited Neanderthal genes have been identified. No, no. There's a handful or a little bit more of associations. are kind of very well studied and there are more that we believe we will find.

Let's talk a bit more about your specific study now. So how exactly did you go about finding this fact? 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 even the ICU or even die from the disease. And I've been a small part in this consortium. And then I also worked with a Neanderthaginom and I decided to, why don't I have a look? And it was really, I fell off my chair.

It was really a surprise. So I just had the two days. data sets at hand at my computer. When comparing the major, the biggest risk specter, I saw immediately it was a Neanderthal sequence. It was really striking. So after reading your paper, this is involving chromosome three within the human genome. So can you just give, for those people who don't know,

a bit of a background on what chromosomes are and what their function is, just very briefly? So our human genome consists of 23 chromosomes, and we got two coppers of each. Or if you're a male, you have actually one X and one Y. And this is molecules, this is chunks of DNA in this organized in chromosomes. So all of them contain genes. and some genes are on chromosome 3. Okay.

So what specific functions do the genes that you've identified play in the human body? So this region contains several immune receptors, receptors that are involved in signaling during immune response. So that's very intriguing and interesting in this case. There are also a gene that forms a complex with the receptor for the virus, which is also of high interest, of course. Okay, so you mentioned that the risk is bigger in carriers of these genes. So how big actually is the effect? So initially we saw that it was about 60% increase per copy. As I said, you can one chromosome from your mother and one from your father.

Later, the study has actually put that increase a little bit higher, so that's almost twice the risk if you carry one genetic variant. And 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. Okay, so is it, have we been able to identify the prevalence of specific symptoms in the carriers of these genes? So this genetic variant, we should say there's not Neanderthal genes, but Neanderthal gene variants. So there's not new genes from Neanderthals, but rather genetic variants. And we see that carrying this genetic variance is much more common in people that end up in hospital

and ended up at the ICU. So those that have a bad progression of COVID-19. One study also studied so that it was an increase in need of mechanical ventilation. So we don't believe it has so much to do with susceptibility of the likelihood of actually attracting the virus, but rather how the body respond to it. Do we have any idea as to why this is the case? So it might be this immunoreceptres, and we know that people that get very sick in COVID-19, they seem to have that people have heard about this cytokine storm, some overreaction of the immune system.

So this might be part of that so that the body responds too aggressively against the virus. So are there any sort of precedence 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 us in a certain direction with this. research in the future? So in terms of Neander tells a cluster of also a porto receptor that I've studied before. Most in 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. Okay. So now that we've we've, 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 that are more at risk, or we could expediate certain patients' treatment in thanks to having this knowledge? Yes, indeed. So 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. And as you point out, it could be, we and many others are trying to understand this genetic variants and to see which one of the genes in this region is important.

And some of these receptors are actually what we say, drugable. So that could point towards future treatment for COVID-19. in. And also as equating what you said, risk stratification to identify people at risk might also be very important in dealing with this disease. Okay, so just one final question then. What are your plans, do you have any plans for further studies or moving this research on in the future? Yes, indeed. So we are studying the legacy of Neanderthal interbreeding in general. And for this particular locus, we and many others are trying to look more into detail about the mechanisms at play at this locus, this position in the genome.

Okay, brilliant. Well, best of luck with all that in the future. Thank you so much for taking the time to speak to me. Okay, thank you so much. Nice to be in the show. Thank you for listening to this episode of the Science Focus podcast. That was geneticist Hugo Zeeberg, talking about his research on the carriers of Neanderthal DNA, suffering from more severe effects of COVID-19. For more on the coronavirus and all other things, science, check out the latest at sciencefocus.com.

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