Science Friday - Your Pain Tolerance May Have Been Passed Down From Neanderthals

Episode Date: July 11, 2024

There’s a little bit of Neanderthal in most of us. Neanderthals and Homo sapiens had a long history of intermingling, before the former went extinct about 40,000 years ago. That mixing means most modern humans have some amount of Neanderthal DNA—and it accounts for up to 3% of the genome in some people.While these genetic remnants don’t have much impact on our day-to-day lives, they may be responsible for one surprising effect: pain tolerance. Recent research shows that people with Neanderthal variants in the gene SCN9A have a lower pain tolerance than people without the gene.This isn’t the only Neanderthal remnant that’s been passed down. A study from earlier this year pinpointed a certain genome region that impacts nose shape. Taller, wider noses were passed down from our Neanderthal ancestors who lived in colder climates. A larger nose warmed air before it hit the sensitive lungs. Ira speaks with Dr. Kaustubh Adhikari, assistant professor of statistics at the Open University in the United Kingdom, who worked on both of these studies.  Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

Learning about our distant past isn't all about digging in the dirt. What really drives our work is really curiosity, I would say. It is just as if you do an archaeological excavation to find out about the past, we sort of make excavations in the human genome. It's Thursday, July 11th. It's also Science Friday. I'm John Dankowski, and that was the voice of Nobel laureate Savante Paavo. Back in 1997, on this very date, his team was the first to sequence DNA extracted from a Neanderthal specimen. It was research they published in the journal's

cell. My biggest interest is actually to study the genetic differences between present-day people and our closest relatives in Neanderthals, particularly genetic changes that exist in everybody today or almost everybody. And that may be important for why modern humans became so numerous, foreign big societies and so on. That research led to some really remarkable findings. like that there are billions of people who carry some percentage of Neanderthal DNA. This work has spun off more research that traces Neanderthal genes into our neural processes and immune system. And in this archival interview from last November, we also learned that Neanderthal genes might even affect how we feel pain. Here's Iroflato.

There's a little bit of Neanderthal in most of us. Neanderthals and Homo sapiens had a long history of intermingling until the former when extinct about. through 40,000 years ago. That mixing has led to some modern people having up to 3% of Neanderthal DNA. And while these genetic remnants don't have a lot of impact on our day-to-day life, it may have one surprising effect, pain tolerance. Joining me now to talk about new research in this field is my guest, Dr. Kostobadakari, assistant professor of statistics at the Open University and the United Kingdom. Welcome to Science Friday. Hi, Ira. Thanks so much for having me.

Nice. Thank you. So there is some Neanderthal in most of us? It is indeed. So most people in what we call Eurasia and the Native Americans, we all have some ancestry from ancient human cousins called Neanderthals and also another related family called Denisovans. That is cool. Let's get right into your study. There are different kinds of pain, right? the pain I feel when I stub my toe. It's like different from chronic back pain, for example. What kind of pain were you looking at in this study? Yeah, exactly. So we were looking at normal pain sensitivity or pain perception. And as you said, if we end up touching a hot pan while cooking,

we want to feel that pain because that then keeps us safe, not burning our hand. And that is very different from chronic pain, which is not so good for us, and is in fact something that healthcare systems spend billions trying to manage and treat. So we were looking at the first kind of pain, which is the normal pain perception, and that would vary a little bit between people to people. So that's what we were studying. And for the people who have these Neanderthal genetic variants, just how much of a difference in pain tolerance was there? It wasn't a lot. So because we are talking about normal pain perception, so for example, if we touch a plate, that's our body temperature, we won't feel pain. But if we start increasing the temperature

slightly, at a certain point, I will say that it's starting to feel hot and then we will stop that experiment. So it's that kind of sensitivity we are talking about. That's one particular kind of pain perception or pain sensitivity we are measuring. And that would vary between people, say you may feel that at 40 degrees Celsius, I may feel that at 42 degrees Celsius. So it's a relatively small variation. And correspondingly, the Neanderthal contribution we saw were at this relatively moderate amount as well. But that is noticeable enough once you study a large enough group of people. So the Neanderthals had a lower pain threshold. Do we have any idea why that would be? That is a very interesting research question, which unfortunately we haven't figured out yet.

and that's part of the next step in our research. So it certainly did something because we see that particular bit of gene that we inherited was under positive natural selection. So it certainly gave us some sort of advantage, but we don't know exactly what it was. If Neanderthals had a lower pain threshold, would they have to be a little more cautious in how they live their lives? Well, that's a good question.

Might have been. So we don't exactly know what would the ramifications be in people's daily lives. As I said, it's a relatively small variation. And essentially, every gene our body does a lot of different things. So it's not necessarily that pain was the ultimate outcome characteristic that was influencing this natural selection. It would have been some other function of this gene. So it's a very interesting question. We don't know the answer yet, I'm afraid.

Do you think that because we humans survived with a little more pain tolerance, it increased natural selection toward us? That is possible. There are hypotheses that even between different groups of modern humans, there are variations in pain tolerance, and that might have some advantages. So a common example is malaria, for example, that there are selective advantages of people having malaria protective genes in certain parts of the world, and that might have been helpful. Right.

So something similar could have happened. So we know that these near-and-ethal people lived at colder climates, and they had various adaptations that helped them survive in these colder conditions. So we also know that they passed some of those genes that conferred these evolutionary advantage to modern people living in those areas. So might have been the same story with these pain genes that. something like that happened, but we exactly don't know yet. Very interesting. A few months ago, you found that nose shape is dictated by Neanderthal genetic

variations. Tell me about that. What you found there? So that was studied with the same group of people. What we do is, so that's how we found that there were certain changes in certain genes that modified our nose shape within, of course, the range of normal human variation. And when we did that, we found certain genetic changes in certain genes. But we also looked at whether we could have inherited those genetic changes from Neanderthals or from Denisophon's, the two ancient groups of humans we intermingled with. And when we did that, we saw that there was one particular gene which was influencing our nose height, which we seem to have inherited from the Neanderthals. and again there was probably some evolutionary advantage of having that particular genetic change.

And we hypothesized that because the Neanderthals started living in these colder northern climates about 400,000, 300,000 years ago. They were much better adapted to that climate already when modern humans started to move in. So it's quite possible that when we intermixed with them, we said, oh, these genes are already giving you some advantage to living in these climates. We'll borrow them. And we did. And that's what we postulate in this paper. What kinds of noses were inherited from Neanderthals? I was looking up Neanderthals and it seems they had longer, broader noses.

Was that an advantage? What kind of advantage did that give them? So what we hypothesize, this is not something. we can do an experiment to improve but what we hypothesized in our study and in several other studies by other research groups is that when you have a colder climate where the air temperature is much lower you don't want that very cold air to reach your lungs directly so what you want to do is heat up the air a little bit when it passes through your nose and your breathing to you so if you have a nose shape which gives you a bigger surface area inside

that helps to warm the air more. So that is what we think is the reason. There was this other species, the Denisovans. They were also early hominids. Do we know if modern humans have their genetics too? Yeah, we definitely do. So we have recovered DNA from Denisovans. And when we compare that to worldwide populations of modern humans,

several groups have them. So East stations, Southeast stations, Native Americans, there are certain parts of Southeast Asia, which have up to 8 or 10% of Denisovan ancestry. So that's quite interesting. Wow, that is interesting. Is it possible that if you have Neanderthal or Denisovan genetic variants, if someone is curious about it, is there some testing panel? Can I get it tested to see if I have those genes? I don't think you can get it tested directly from the consumer genetic tests. So this is a slightly more sophisticated genetic analysis that we do. But I think it's

possible. So these testing companies might one day be able to implement these comparisons to say at least overall what percentage of your DNA could be netheral or could be dynosophon. I think a couple of companies might do that already. But if you wanted to look at specific variants, whether those are inherited from Neanderthals or Denisovans. Right now, we know a fair amount about certain genetic variants. So these companies may one day decide to put those variants on the chip, and then at that point you would be able to find out. Is it possible that there are more Neanderthal or Denisovan genetic variants out there

than that we just don't know yet about? Yeah, there's certainly that possibility. So you know that globally there are many populations that are understudied and there have been research efforts to increase representation in genetics research. So if that happens and we study more and more groups of people around the world,

we'll probably find out more about it, yes, certainly. And as far as the pain threshold, there's no way that I could know just by maybe being more sensitive to pain that I have that Nanditol variant gene, could I? I mean, what you're saying is it's really not that striking a difference? No, you're completely right.

It's not that striking a difference. So there are certain characteristics and certain genes which are linked in a very obvious way. For example, whether you are able to digest milk or not, usually in Europeans' populations, that's down to a single change in a single gene which gives you the ability to digest lactose. So those are examples in which is very obvious. and if I see that you are able to digest lactose or not, I will be able to see if you have the genetic variance or not. It doesn't work that way for most of the other characteristics that we study, like height, like face shape, like pain. So there would be a lot of genetic changes in a lot of genes that each give you a very small advantage or disadvantage,

and therefore it is very difficult to say. I mean, the other thing, of course, is that there is a huge effect of environment as well. So, for example, when it's a colder climate and you stub your little finger on your feet, it feels worse. So there would be those kinds of variation. Or, for example, for height, you know, nutrition has a huge effect on height. So, of course, there would be, in general, a lot of difficulty in trying to link a specific characteristic to a specific gene. Right. Well, next time I stub my toe, I can't say, darn those Neanderthal genes in me.

Indeed. Fascinating. That's about all the time we have today. Thank you for taking time to be with us today. Thank you for having me on the show. Dr. Costa Badakari, assistant professor of statistics at the Open University in the UK. Thanks, Ira.

That's all the time we have today. As always, there's a lot of people who help to make the show possible, including Santiago Flores. Dee Petersmith. Full of Samares. Thanks, everyone. Tomorrow we're going to wrap up the week's top science stories, and we'll try to see if we can use science

to stop my cat from scratching the furniture. Find out more. Hope you can join us. I'm John Dankoski.