Mind & Matter
Mind & Matter
Evolution & Genetics of Human Diet, Metabolism, Disease Risk, Skin Color and Origins of Modern Europeans | Eske Willerslev | #154

Evolution & Genetics of Human Diet, Metabolism, Disease Risk, Skin Color and Origins of Modern Europeans | Eske Willerslev | #154

Download, watch, or listen to M&M episode #154

About the guest: Eske Willerslev, PhD is an evolutionary biologist and Professor of evolution at both the University of Copenhagen and University of Cambridge.

Episode summary: Nick and Dr. Willerslev discuss: human evolution out of Africa; the origins of modern Europeans; hunter gatherers, early farmers, and pastoralists; genetics of human disease risk; evolution of diet & metabolism; evolution of light skin color; and more.

*This content is never meant to serve as medical advice.


Full AI-generated transcript below. Beware of typos & mistranslations!

Eske Willerslev 2:25

I'm calling in from Lagos just north of Copenhagen, Denmark. So I'm both a professor here at University of Copenhagen and also at the University of Cambridge in Britain. So that they are tomorrow I'll head off to Cambridge.

Nick Jikomes 2:40

And are you Danish? Originally?

Eske Willerslev 2:43

I'm Danish. Yes, exactly.

Nick Jikomes 2:45

Well, by birth, yes. Can you tell everyone a little bit about who you are? And what you do as a scientist? Yeah.

Eske Willerslev 2:51

So I'm an evolutionary biologist. And my primary tool is what we call ancient DNA. Right. So it's it's genetic information from the past. And we're both retrieving such information from human teeth from animals, but also, from ecosystem, entire ecosystems by retrieving it directly in a directly from ancient soil. So we we are, you can see, using this tool to address quite diverse questions, everything from you can say, human spread across the world, you know, changes in lifestyle with humans, to the extinction of the last big portrait mega fauna, I mean, the big part of mammals in the end of the last ice age, to you know, how ecosystems are changing. And right now, actually, my focus is to try to take some of these changes from the past adaptive changes, and then see if we can get them into present day crops to make them more resilient towards climate change, for example. So it's, we also look at pathogens, human pathogens, so it's very diverse, you can see what we're doing. But the toolkit is a most parts, this ancient DNA

Nick Jikomes 4:22

in terms of looking at ancient human DNA, one so in one sense, you're looking at things that are very old, you're looking at, you know, humans that were around 1000s 10s of 1000s of years ago, in another sense, you're looking at actually recent human evolution, because it's, it's a much more recent picture of how humans changed just in the last few 1000 years, compared to say, someone who's studying like Neanderthals or humans from millions of years ago. So when you're studying humans, that, that we that are our ancestors 1000s of years ago, 10s of 1000s of years ago. What's special about that time period, and how do you actually How do you actually obtain this DNA? Yeah?

Eske Willerslev 5:02

Well, it's a you can see, it's, you know, a lot is happening within the last 10,000 years of you can see human history, human evolution, right. It's, it's the period where we are undergoing the changes in different parts of the world from being on the gathering, which we have been, you know, since we emerged as a species around 600,000 years ago, into new lifestyles. So, so in terms of lifestyle, there's not that much you can say, it seems that is changing until around 10,000 years ago, and then everything changes. And so therefore, it's, it's a very, you know, this more recent, if you can say, the more recent part of, of human history and human evolution is actually very interesting. We are, we are getting a DNA from all kinds of ancient skeletons. So it's really, you can say it's from collections that has, in some cases existed, you know, for more than 100 years in, in various museums, sometimes we also participating in excavations ourselves, I mean, so basically getting the material fresh out of the ground. And there's really two types of materials from humans we are particularly interested in one is teeth, because teeth, has in general, pretty good preservation of DNA. But they also we have learned, they also contain DNA from the blood borne viruses and DNA viruses and bacteria that the humans were carrying at the time of death. So

Nick Jikomes 6:46

you can, you can get a picture of not just the human DNA, but the pathogens that they were interacting with.

Eske Willerslev 6:51

That's exactly right. And the other piece is what is known as the petrous bone, which is basically fused to the inner side of your skull is part of the year. And that's the most dense bone in the human body. And therefore, it's particularly well preserved the DNA they are part opposite the teeth, you are, you're normally not getting, there's not much of blood flow in the petrol, so you're normally not getting the pathogens. So the beauty about the teeth is if you can get DNA out of the teeth, you're both getting the human as well as the pathogen that humans were carrying at the time of death.

Nick Jikomes 7:29

And when you recover DNA is this typically nuclear DNA of the full genome is this Mitochondrial DNA is it both?

Eske Willerslev 7:40

It's both. So we are been saying for many years now, my team actually did the first ancient human genome, back in 2013. And that was, you can say, a major achievement at the time. But they, you know, due to a sequencing technology, and, you know, drop in prices of sequencing, etc, I mean, we are basically shotgun sequencing, all materials we're getting right from human. So depending on the DNA preservation, you can get either, you know, what we will call a low call rich human genome, which means not every position is covered once, but still, you know, it's kind of covered across the genome, a, and in some cases, you will get like, even fairly high call rich human genome, if, if the DNA endogenous DNA allows for it. And at the same time, when you're doing the shotgun sequencing, you're also getting the mitochondria. Because the mitochondria is present in many, many more copies per cell than any fragment of of nuclear genome, right. So we will typically get a very high coverage of the mitochondria. And then obviously, you will get anything else which are in there, it can be soil, bacteria, viruses, fungi that have penetrated the tools after death, but also the human pathogens that has been deposited through the blood flow has been deposited in the cement some of the teeth. So you're getting all that by shotgun sequencing. And this is what we do. If you're then a particularly interested in a certain Britain, where you want a higher call rate, you can then additionally do what is known as a targeted capture, where you go in and try to pull out, you know, as many copies as you can of this particular piece of DNA you're interested in.

Nick Jikomes 9:39

Before we get into some of the the interesting findings that you have uncovered over the years, I want to talk about the quality of the data and how we know that we're actually looking at the DNA that was present in these people. So when you recover samples, you know, you've got a copy of the genome in every cell and then as you said, You've got many copies of every mitochondrial genome inside of every single Sal, so, you know, when we think about the preservation of DNA and how much it degrades over time, are you able to just sort of like, figure out what the what the real genome sequence was, because you've got multiple copies in every cell and every mitochondrion. Yes. So

Eske Willerslev 10:16

until we got what is known as this next generation sequencing, where you do the shotgun sequencing, the biggest problem for for any ancient DNA work, but particularly in in human DNA work was contamination with modern DNA, right? Because the DNA in any ancient specimen is highly degraded, it's fragmented into short pieces very often is the is the majority of the DNA may be in the range of 30 to 50, base pairs, long, so very short pieces, and there's also very little of it. And therefore, in the old days, you know, where where you use kind of traditional PCR, then the shortest fragment of DNA, you could amplify. And still, you can say have some information, of value would be around 9200 base pairs. And, and because the vast majority of the DNA is actually of the ancient DNA of the endogenous DNA is shorter than that, right? You, it became a numbers game. I mean, if you had very, very little DNA that was that length, or longer, then very often, it would be swamped by contaminant DNA, right, and there was no way to really distinguish the two. But with next generation sequencing, you can target these very short pieces of DNA. And those this you can say, if you imagine this, this reverse relationship, exponential relationship between fragment length, right, the length of the fragments, and copy numbers, you know, number of copies of endogenous DNA. So as soon as you went very short, suddenly, the amount of endogenous DNA just increased enormously, right? Accumulation just just by that exercise, became way less of a problem. But then secondly, you know, it's clear, because you preserve with shotgun sequencing, you're serving the cermony of the read, of the DNA reads, so it means this is the place where it's particularly attacked by DNA damage, you know, termination of cytosine. So you can see that DNA damage, so we can actually see which one is a damaged ancient fragment versus what is most likely a contaminant. And then finally, because next generation sequencing allows you to produce this enormous amount of data, I mean, full genomes, right? Then you also have a statistical power to ask, for example, let's say you have a male, right, I mean, how many Y chromosomes? Do I have? A, you should only have one, right? Is there something additional and you can quantify, then the amount of contamination that additional is, and you can basically take it into account in your downstream minutes. So shortly, I mean, contamination that was a huge, huge problem for decades, is really becoming you can say, a minor problem today in the field.

Nick Jikomes 13:27

And so it sounds like an early an early part of the research process for for your team is literally stitching together genomes, so the genome is fragmented. And you have to you have to piece it together like a puzzle, almost. Yes.

Eske Willerslev 13:41

So we do this by using a reference genome, right? So use them, you can say, a modern human genome. And then you basically take all your small pieces, and see where do they stick, right. And what is quite surprising is when you have something down to, let's say, 50, base pair fragments. It's in the range of, I think, 70% or 80% of the human genome, that way, you can uniquely map these very short fragments. So even if they're short, you can uniquely map them. I mean, the kind of the cut off is around 30 base pairs, when you go below 30 base pairs. You know, there's multiple places they can, can stick in the genome, right. So so normally the cut off for what we can work with is around 30 base pairs by party. So this is what you do. And then more recently, you know, we and some of our collaborators has used very successfully what is known as imputation. I mean, so if you imagine you have you have a kind of this, you can say genome of an ancient human portals, a number of holes in it. There's a number of places where you don't have information and you can actually based on on knowledge about populations and the frequency of different bases in the genome, you can actually predict with very high security, what are these missing bases. So it means you are almost at a stage where almost where an ancient human genome is as good if you want of quality as that of a modern living, modern human being.

Nick Jikomes 15:28

Okay, so you have almost as much confidence in in the genome sequence from people living 1000s of years ago, as you would if you sequenced my DNA tonight, basically, yes. And so, I want to talk to you about fairly recent human evolution, but I want to, I want to give people a sense for what we're talking about, for when certain things happen. So I want to I want to start to build a picture for people right now, help them triangulate certain things in their mind. So all of us have a common ancestor that came out of Africa. When did human beings first emerge out of Africa, human, Homo sapiens emerge out of Africa? And were those human beings what we would consider anatomically modern human beings? And what does that even mean to you? As an evolutionary biologist? What is a modern human being? Yeah,

Eske Willerslev 16:17

no, is this good questions? So I mean, it's, it's generally believed, right? That you can say, the lineage leading to modern humans and the lineage leading to modern day chimps, which is our closest, present the relative, right, this is they are diversifying from each other, it means they start evolving in two different directions. Sometimes around 6 million, maybe a little older, a million years ago, right. And on you can say on, and this is happening, believed to have happened in Africa. And, and, and, and the evidence behind this is mainly, you can say, of traditional fasade character, you'll find basically, you can say early types of humans, which are not anatomically modern human or our species, but you can say things that are believed to be on the human lineage, right. And along the way, you know, a number of different hominin types, human types, if you want, early human types are merging. I mean, we have Australopithecines, we both have rational and robust forms. So one should imagine a world where there's more than one, you can see type of human in the landscape, right? So you even in Africa, you actually, it seems to be that you, you can have a, you know, different types of hominins. Where, well, if you, if you looked at them, you will probably recognize Well, it's some kind of human like creature, but if they met each other, they will be quite distinct from each other. Right? And so, so this process kind of continues, and it's not, you know, it's not different from what you see in other mammals, right? I mean, it's, you see different types pop popping off, right. You know, some survives, some are replacing others, et cetera. So, you know, we along along that route, you can say we also see very massive increases in brain size, right? There's still debate whether this increase is something that happens very rapidly, because that's how it looks in the foresight record, right, you're going from one group with a very small brain to suddenly one which has an ultra brain, but that could also just be a result of the fossil record itself, right? You don't have any everything from the fossil record. So there's no discussion, you're gonna know, how fast does does this happen? But it happens. And there's a couple of instances where you in the fossil record, see kind of the toppling of the brain size, right. And we also learn along the way to have some kind of tool use, right. And the first of these hominins that seems to have left Africa, as far as we know, is what is known as Homer racers, right? So it's, it's, as far as I recall, it's around you know, a million to half a million years ago, something like that, but they, we they are the first ones kind of getting out of Africa. And also the first ones that we know of that you can see having fire for example. They had they have a substantial smaller brain than we had. We have but but they you know, a very thick eyebrows, etc. But you see them both within Africa and in in Southeast Asia. Then you can say the second group that seems to be leaving Africa As far as we know, seems to be a Neanderthals, right, which is, you can say the a group of hominins, that that has actually been genome sequenced. It's the only, I would say, only hominin, that has really been genome sequenced besides modern humans. And that certainly have a capability of producing tools, etc. And then you can say then, in terms of our own species, Homo sapiens, the anatomically modern human, well, based on mythology, this is based on mythology, you find skulls, if you want that looks like modern humans, sometimes around 600,000 years ago in Africa, in and in Africa. Exactly. And the, you know, we are then leaving Africa, there's a lot of debate whether there's been attempts, early attempts to leave, you know, maybe you have, you know, samples, for example, from Israel, you know, which are dating around 120,000 years ago, a bot bought these. In any event, it doesn't seem like these early attempts, if they have been there to leave Africa have given rise to two non Africans today. So, it looks like the migration that kind of give rise to all non Africans, as far as we can see, is migration out of Africa happening sometimes between 90,060 1000 years ago. Okay,

Nick Jikomes 21:39

so, so 90 to 60,000 years ago, is when we think humans left Africa, the humans that gave rise to all non Africans, left Africa, there may have been attempts of anatomically modern humans to leave before them, there probably were, maybe they just didn't spread very far. Maybe Maybe they just died out. But you're talking over half a million years ago, you've got anatomically modern humans, and a little under 100,000 years ago, they leave Africa eventually give rise to all non Africans. Yes, that's right. It wasn't when that group left Africa 60 to 90,000 years ago, our ancestors were talking about what was the earth? Where did they go first? And what was going on geologically and ecologically was that during an ice age? What was happening? Yeah,

Eske Willerslev 22:26

it's a good question. I mean, so. I mean, it seems like there's still debate from where they came out of Africa. Was it out of North Africa? Or was it actually further to the south? It's Bob Ludwig. And and exactly what are they doing out there? And why? How can it be that they're first so successful? quite late? I mean, think about it, right. Modern humans has, presumably originates around 600,000. I mean, it's a long time, right, that they have stayed in Africa, hundreds of 1000s of years. Yeah, exactly. So So there has been different. I mean, nobody knows for sure, right. But some of the some of the assumptions has been that Neanderthals that had left Africa at that point, you can say, we kind of occupied the regions outside Africa, and made it difficult for modern humans to really establish themselves outside Africa. And the, you know, at the time, when modern humans didn't successfully leave and give rise to present day humans, outside Africa, it's a time whether the under tiles are already in massive decline. I mean, so that's, that's one interpretation.

Nick Jikomes 23:44

I would imagine, too. I mean, if we're coming out of Africa, I would imagine that much of Africa for much of this time, was habitable and fertile and had plenty of food. So maybe there was not a lot of need to leave. Yeah,

Eske Willerslev 23:59

it's a good question, you know, but then, and this is kind of the traditional, I guess, view of how to look at a modern human, anatomically modern human Well, we are kind of a sort of an animal that are basically going for resources, we're staying in the same place until the resources are depleted, and then we move on, right. But I would say some of our more recent studies, for example of peopling of the Americas, I think is really challenging that. Because this is also basically Stone Age people. It's a group of hunter gatherers, right coming into the Americas, and injuring completely on habitated continent. And you'd hope to our great surprise, I mean, as soon as they have bypassed the so called Pleistocene ice caps that at that time we're covering most of of Canada and they get south of the ice caps. Coming within, within 1000 years, right, they are all over North and South America. They across the Rockies, they have you know, they have adapted to a everything you know, from Desert to tropical regions, etc. So it's not, it's very hard to see that the behavior is a result of you can say depleted resource. Yeah, they're not

Nick Jikomes 25:26

just staying somewhere until everything's gone leaving, they're moving the whole time.

Eske Willerslev 25:29

Moo, moo, moo, explore, explore, explore. And, and to me at least it suggests that that at least early and tropical modern humans are not that different from us. Right? Why do people climb? You know, Mount Everest? Right? There's no, well, there's no reason for it in terms of resources, right? They do it because the curious they want to understand this is what is typical of our, our species, right? Is we are exploring, right? And we adapt.

Nick Jikomes 26:01

We have we have the physical and physiological capability to move long distances to go into different climates. And then we also have the mental proclivity to want to just see what's over there.

Eske Willerslev 26:12

Exactly. And, you know, you see people we can also see from the early modern humans that left Africa, right, I mean, what happens to them? Well, the first one we know of, which still have descendants today, that are kind of taking off, if you want from the rest are kind of saying, well, we want to explore the world. You know, we want to see what's out there. That's that as far as we can see that the ancestors of Aboriginal Australians and Highland Park that happens. So they they kind of say bye, bye. To the rest. It's already something like 70 80,000 years ago, where you can say, our ancestors, European and Asian ancestors kind of stay put they stay in the same room and

Nick Jikomes 27:01

stay put, where would that be like in the present a Middle East? Roughly?

Eske Willerslev 27:05

It's a good question. Nobody knows for sure. But the assumption is, it's somewhere roughly in that area in that area. Right. Okay.

Nick Jikomes 27:13

So so you got a population that lives in Africa, it gets to roughly that general region? Yes. Heart of that branches off if presumably, follows the coast to Australia.

Eske Willerslev 27:23

That's the assumption, you know, they follow certainly Southeast Asia. That's the idea. And they make this incredibly journey, right, which is, is remarkable, really, I mean, they are, they're crossing Asia. And they're crossing from mainland Asia into pathway and Australia, which at this time, are connected together, but still isolated from the mainland, right. So they're basically crossing the ocean already around 60,000 years ago, presumably, but presumably by boat, and they do it, you can say with the sufficient population that they can establish themselves. And they keep going basically, on to the present day, right. So this is a remarkable journey. And then you can say, Asian and European ancestors at this time that doesn't exist Asians, that doesn't exist, Europeans, neither, not genetically, they're not separated from each other. But around 50,000 years ago, you see that as different groups taking off, right? So one group becomes if you want, present, the Europeans and other groups become present the Asians and then there's a third group that we actually didn't know about until we did ancient genomics. You know, it's a group that just after the Asians and Europeans are splitting from each other, around 50,000 years on the European side, are basically branching off and this group is occupying most of North and Central Asia, as far as we can see. And these, this is the group that becomes one of the main groups that are ancestral to Native Americans. But it dies out, you can say it dies out in in Asia. Later on, so we, we were not aware of it. I mean, we basically, you know, everybody thought Native Americans is a group of Asians, right. But in fact, what we can see is that Native Americans is the meeting between two different populations and Asian population that are meeting this very ancient group of people that are living from Mammoth hunting and hunting of woolly rhinoceros, etc.

Nick Jikomes 29:45

Okay, so, so by 600,000 years ago, anatomically modern humans have evolved in Africa by about 90,000 years ago, they have left Africa, somewhere in roughly the Middle Eastern region. Roughly speaking, by about 70 80,000 years ago, so shortly after that, some of those people branch off, and they become the Australian aborigines of today. So they travel to the east and down that way. So 60 70,000 years ago, that's happening. And there's no white people in Europe, there's no Asian peoples. We think of them today that hasn't emerged yet. No, exactly.

Eske Willerslev 30:22

And so then you see this kind of emergence, as I said, 50,000 years ago, you start seeing the emergence of what becomes the Asians and, and Europeans. But I mean, what probably many people don't realize is that, you know, Europeans, and Asians have no, I mean, today, we think about Europeans or in Europe, Asians are in Asia, right. That's how we look at it. And, but when you go back in time, it has not always remained like that, you know, so there has been plenty of periods where, you know, large part of Asia was actually occupied of genetically speaking European populations, and also periods where Asians are moving, for example, you know, they are in North Asia, and then they're moving into Southeast Asia, kind of mixing up with, you can say, the, some of the, the people who were left behind, when people crossed into Australia, it's not like everybody went to Australia, right? We, so it's, you can say, the world that we know of today, I mean, the world that you and I and everybody else learned in school and see, you know, Asians in Asia, Europeans in Europe, you know, this is a very, very young world. It's for for the you can see the whole genetic composition of present day Europeans. You can see the main, the main characteristics, if you want is formed within the just the last 5000 years. And when we go to Western and Central Asia, we are only back in the medieval times. I mean, right, around 1000 years ago. So it's the it's one of the things that ancient genomics really have, I think there's two things that it has really changed our minds with compared to what we generally thought before. One is that people are super mobile, right? I mean, there was this notion that, that when we left Africa, we went to the different parts of Europe, different parts of Asia, etc. And then we kind of stayed put, you know, wherever we went, right. And when we had a cultural change, it was always because the same people learn to do something new. Right? So when you went from a hunter gatherer to agriculture in Europe, it was because you learn to do something new, right? But it was the same people who basically state and ancient genomics have very clearly shown this is not the case. I mean, people have been super mobile. And many of these, you can say, historical transitions, or prehistoric transitions from on the gathering to farming from farming to Bronze Age, from wrong seats to Ireland, H, from Ireland, H to Viking period and so forth, is actually a result of migration of people. I mean, new people entering an area meeting somebody else, mixing up with them, right, transferring different types of knowledge with them, so so. So the world, you can, as I said, the world that that we observe today is is very, very young. I mean, for most parts. So

Nick Jikomes 33:49

50 60,000 years ago, I think you said, that's when the populations that gave rise to present day Europeans and present the East Asians first started diverging. So at that time, 50 60,000 years ago, everyone's still had like, dark skin.

Eske Willerslev 34:03

Yeah. Yeah. As far as we know.

Nick Jikomes 34:06

And were they all still like hunter gatherers at that time? I wonder the take from them to get to the first farming societies? Yeah.

Eske Willerslev 34:15

So I mean, the first farming, there's still debate about exactly when you see it, right. But, you know, something around 12,000 years ago, is where you see the early attempts. And it's happening in the Middle East and Near East, right, where you both domesticate plants and animals. And then there seems to be an independent domestication event, if you want of rice happening in in the Yangtze region in China. And you also see close to the same time, same time period, maybe slightly later. You see the domestication of corn in America, right. So you have you can say you have these kind of three to me is the occasion events in the world that, as far as we know, have not much to do with each other, it happens kind of independently, more or less independently, but very closely around the same time.

Nick Jikomes 35:12

I see. So farming probably didn't develop one place and then spread for a cultural transmission from there probably was independently discovered in different time, times and places. Exactly.

Eske Willerslev 35:23

And and for many years before ancient genetics, the general notion was that yes, it was developed in these different places, but it's spread as culture. Right? It was not by humans, it was spreading by culture, you know, I heard from my neighbor that heard from his neighbor from his, his, his his neighbor, all the way down to the Middle East. Well, you can do this, right. So I learned in school is can you derive from the Stone Age man in Denmark, direct lineage up to today. And for both, where we have really done some investigation on this is for Europe, and is from for Asia. And in both cases, the story is wrong. So it's very clear that the, that domestication practices are being spread by humans moving. So what humans moving from the middle and Near East up through Europe, particularly Western Europe, and its peoples from the youngster region in in China moving south, right into Southeast Asia, bringing with them rice. And in both cases, you can say it resolved in, in some places by a mixture of the two populations, I mean, the hunter gatherers and and you can say the farmers, right. And in some regions, we can also see that it actually resulted in a replacement. I mean, it means one group is is basically killing off or replacing another group. So in Denmark, for example, where you have the most skeletons from this transition period, I think anywhere in the world, really, they are everybody first thought, Well, okay, it's it's just, you know, farmers entering Denmark in the end, and then mixing with the Danes. But more recently, we could see, when we seek with a lot of these, this is not the case, what happens is they're coming at mixed from the south, right? So we can say there was happy days in the south where hunters made farmers, they mixed, got children, changed to become agriculturalists. And then when they these guys move further north, and when they move further north and get into northern Germany and Denmark, at least, then they replace all the original hunter gatherers within one to two generations. Right? So, to me, at least, we don't know exactly how it happened. We don't find any pathogens. So it looks to me like it's some kind of genocide, to be honest. So so. So it varies from region to region, exactly what happened. But it's very clear, it's this kind of movement of people bringing with them new technology, right.

Nick Jikomes 38:14

When people in the middle eastern region that eventually become the Europeans start to move into the geographic region of Europe as we define it today. When did that start to happen? And how much of it had to do with receding glaciers or the Ice Age or climate climate change?

Eske Willerslev 38:32

Well, I mean, at that time, you can see when this is happening, it's starting around 10,000 years ago. And at that time, you are well into what we call the Holocene, the bombing period we're living in today. So the glaciers have disappeared, right? I mean, it's, it's, it's, you can say it, it's a non plushie that landscape that they're moving into, so it hasn't really much to do with the glaciers. I mean, the glaciers play a role earlier, in terms of you can say, the survival of the hunter gatherers in there, you know, and some seems to be surviving in some refugia you know, where those lists are harsh. A and then when the ice retreats, you know, they expanding out and so forth, but the lifestyle remains the same it's and as far as we can see, you know, it's kind of the same people so if you want it's maybe one pocket that are surviving and expanding out but oh, well, it's the same where where you can see the real changes are happening as I said is from around 10,000 years ago, right, because first you have the agricultural is coming. And they have a severe impact right. I mean, you are going from from a diet, which has been mainly you know, meat, fish, berries, roots, right what you would call a stone age diet. Today, some people want to to you No even leaving like this today, I believe it's healthy. But these agriculturalists are basically coming with a diet that is similar to muesli, right to present a muesli. So very rich in carbohydrates, right. And, and the it you can say the the implication of this lifestyle change is massive. So it's both in terms, of course, the dietary, it's in terms of, you know, you go from being very mobile, right, the hunter gatherers are super mobile, they are living in very small groups, right. And suddenly, you become stationary you live in, in larger groups. And we see, you know, massive selection of the so called fats written. So, so fatty

Nick Jikomes 40:52

acid metabolism gene, yes, exactly. So so when

Eske Willerslev 40:55

you when you get when you eat fish and and meat, you're getting long chain fatty acids directly from the diet, right, and you need that for your brain and for your nervous system, etc. But when you eat grain, you'll get it as short chain fatty acids, and the body needs to basically make it into long chain fatty acids. And, and the fats. Richard is involved in this, and we see massive selection. I mean, that means it's a matter of survival, and reproduction by whether you you're capable of doing this. So

Nick Jikomes 41:29

meaning you're seeing selection for the spread of genes that can handle shorter chain fatty acids that you find in more carb rich diet.

Eske Willerslev 41:38

Exactly. That's exactly right. Right. So So you see, so it really changes you can say, the genetic makeup really of, of the peoples in Europe, right? In order to adapt to this new lifestyle. And then, you know, in Europe, you can see then we have in way, it's quite interesting because in, in Western Europe, this is where you see this movement going up, right. But there is actually a client going from, from the Baltic countries all the way down to the Black Sea, where for whatever reason, we don't know why. But you see that the hunter gatherers, on the east side of the client is actually genetically different from those on the west side. And for some reason, you know, the, these farmers from the Middle East, are only really entering on the west side. So the west side gets, you know, so the client between East and West get further deepened, right? Because the the farmers are only going in and mixing with the groups on the west side. Maybe it's something to do with ethnic, you know, culture. They are more hostile, we don't know, but it's very clear. It's not a physical, it's not a graphical barrier. There's not, you know, that should kind of separate the two, but it does. And that barrier actually, first, this solves in the Bronze Age around 5000 years ago, so around 5000 years ago, you had the last major migration into Europe. So now, you know, we have farmers in the West, and on the east side West, they still remain hunter gatherers. So

Nick Jikomes 43:31

so there's like this invisible barrier between them. There's no there's not like a giant mountain. They're separating them with something maybe language, maybe cultures preventing them from mixing. And then you said there's a last major migration into Europe. Yes, who is who's migrating Who is this migrating? Yes. So

Eske Willerslev 43:46

this last migration, major migration is from the pontic steppe, and the pontic steppe is the area, which is Ukraine today, below is part of Bella rock roots and Russia. And the people that that are you can say pastoralists, they are drinking milk. They have you know, big herds of cattle, sheep and so forth. We call this group yamnaya. A, and they are expanding. You know, this is also something that you didn't know before in genomics but 5000 years ago, we see an expansion from this pontics they both northwest into Europe and eastwards into Asia, and they have a enormous cultural and genetic impact in Europe, particularly in North Western Europe. So they are coming in. They are very tall.

Nick Jikomes 44:52

I was about to ask you. Is their stature different? Is their bone structure different? Oh,

Eske Willerslev 44:56

totally. Totally. I mean so, so the hunt the girl was Were quite tall, many of them and they were actually this is interesting. They weren't quite healthy. I mean, when you look at the quite healthy, the farmers are very short, small, generally short and statue and and actually surprisingly unhealthy. I mean their teeth in very bad shape. You know,

Nick Jikomes 45:20

I've heard about this before is that probably because the farming lifestyle the things that they started eating, were driving that unhealthy. Yeah,

Eske Willerslev 45:30

probably probably was part of it at least and, and it's kind of you know, it's interesting to think about right because farming obviously is the lifestyle that wins the battle. Right? And it actually winds not only 10,000 years ago in Europe, but a all across the globe, right? I mean, everybody are eating pizza and drinking Coke, which is just an advanced form of muesli, right? And so farming is winning as a lifestyle. And it's a bit surprising when you look at the hunter gatherers and the farmers, right? Because the hunter gatherer is a super healthy looking the skeletons the farmers look really poor, right? In but evolution, it just reminds us really that evolution is not about

Nick Jikomes 46:22

you know, the physically strongest per se.

Eske Willerslev 46:25

It's getting most kids, right? That's why yes, that's really what it's all about, like, so you can have a pretty horrible life, as long as you get enough kids that survive. I guess the conclusion is? Well, for some reason, the farmers are simply getting more kids that survives. And they're winning this battle, but it means that that the you can see the Europeans after the farmers have been inside I actually much smaller in stature. I mean, they got a lot of farming was

Nick Jikomes 46:58

do you think that was? Do you think that was purely driven by diet and lifestyle, so like Rob pasture is bigger, because they drink milk or their genetic differences? Clearly

Eske Willerslev 47:07

genetic differences, and we can see that the yamnaya, the Bronze Age people, these tall people getting in, very light skinned, right, they also have brown eyes, the hunter, the people they are meeting, they are the in Europe, the dominant eye color is blue, or gray. These guys have brown eyes, they're tall, they have light skin. And we can see genetically we know this, right, we can see that some of you can say these genetic traits that are giving you increase the probability of becoming tall, or coming in with yamnaya. And it makes good sense, right? Because yamnaya Were they really a you can say have a major genetic contribution in Europe, the largest genetic contribution is in North Europe and Northwestern Europe, and generally, Northwestern Europeans are some of the really tall ones right? In Europe. Of course, you can say type determines whether you can you can express your full potential, right? So so if you get a shaped dial, I mean, you can have all these genes, but you will not get as tall as you could have been

Nick Jikomes 48:21

right. But that potential is set based on the lineage.

Eske Willerslev 48:24

Exactly the potential he said. And another thing, they're bringing several things with them, right. They're bringing you know, this is the light skinned the blue the brown eyes, they also a bringing with them the ability to adjust milk sugar as

Nick Jikomes 48:41

adults. Yes, I was gonna ask you about that. Yeah, exactly.

Eske Willerslev 48:44

Right. So so if you look across the world today, I mean, obviously, all babies can drink milk, basically digest milk sugar. But for the vast majority of the world's population, you lose this ability when you when you become an adult, right when you grow up. And and you can actually become kind of ill sick if you if you drink, untreated milk. But in Europe, North Europe, Northwestern Europe, around 80% of the adult population can actually digest milk sugar, right. And this is a trait that seems to come in with yamnaya.

Nick Jikomes 49:27

So they first evolved it presumably because they domesticated animals that could be used to for

Eske Willerslev 49:33

dairy. Exactly, exactly.

Nick Jikomes 49:36

So if that was happening, we're talking like what you said, like 10,000 years ago or less. How quickly did that spread? It must have been very, very quick, which would imply a very strong advantage. Yeah,

Eske Willerslev 49:45

it's interesting because it actually first seems to become high frequent in Europe much later. So it's getting into Europe, round 5000 Something along those lines and And, but it's first in, in really in the irony Ah, it seems to reach high frequencies. So it's 1000s of years later, right? So the, and we don't know exactly why, but maybe there has been some kind of famine, right? Where you can say if you if people slaughter the cow, right, they have maybe one month, one month of meal, if they milk it instead and drink it, you know, they can survive longer, we don't know. But they so it's one of these things where it's in charge, but it actually takes quite some time before it becomes really high, frequent as it is.

Nick Jikomes 50:39

So for a while, there was a few people who could tolerate milk and dairy as adults, but it didn't really spread much. And for whatever reason, it wasn't for 1000s of years before it became much more frequent in certain parts of Europe, at least.

Eske Willerslev 50:52

Exactly. And now today, obviously, it is in northwestern Europe, very frequent. So yeah.

Nick Jikomes 51:00

Interesting. So what other so you mentioned, you mentioned that there's been selection for changes in genes involved in lipid metabolism, how we deal with different types of fatty acids? You've mentioned the lactase persistence thing, the ability to digest milk as an adult that has spread in just a few 1000 years? Quite far, not obviously, there's a lot of people who are lactose intolerant, even today from various parts of the world. So it hasn't spread completely. Were there other major, like metabolic shifts that were happening around this time? And do we think these things are sort of independent? Are they all kind of tied together?

Eske Willerslev 51:36

No, it's very interesting. I mean, we did a study of this, or published something on this earlier this year. So, you know, basically, if you look at all Europeans, right, today, I mean, you can say every European today is really, a, you can say a result of the meeting of these three migration events, right? The hunter gatherers, the farmers, and the Bronze Age yamnaya. Right. That's what makes up Europe, European. So all Europeans can be modeled, as we call it,

Nick Jikomes 52:12

by some combination of those three ancestor, exactly.

Eske Willerslev 52:15

And what distinguishes Europeans from each other northern Europeans, from Southern Europeans, Eastern, from Western and so forth, is how much of each of the three ancestors they carry. So Southern Europeans carry more relatively more of the farmer ancestry. Right. Eastern Europeans carry more relatively more of the of the hunter gatherer ancestry, and Northwestern Europeans carry carry relatively more of the yamnaya Bronze Age ancestry.

Nick Jikomes 52:49

What would you say Northwestern Europe? What countries today? Would that? Well,

Eske Willerslev 52:55

that would be a, you know, Scandinavia, right? The Netherlands, Germany, tastes like that. And what is really interesting is, you know, there's something called UK Biobank, which is really a huge database with all the information that people know about in terms of genotype phenotype relationship, it means, you know, what mutations if you want or variants, a genetic variants are giving you a higher probability of getting tall, for example, or, you know, getting diabetes, or getting multiple sclerosis, or all kinds of stuff, right? I call or whatever. And now, when you have, you can say, the, you know, the or read the genomes of the original populations, right, the three populations on the gallery's the farmers, and yamnaya, then you can actually take their genomes and paint. UK Biobank right and say, well, is the certain traits that arrived with each of these three migrations, right? And therefore has a higher or should have a higher frequency in the different parts of Europe. Right. And there you can see that that well, as I said, this about being told Northwestern Europe coming in with yamnaya, right? A Alzheimer's, for example, is a trait where the genetic variants giving an increased risk of Alzheimer's seems to be coming in with the hunter gatherers. So it should have a higher frequency in in Eastern Europe, a anxiety you know, a is a trade that seems generically come with the farmers right should have a higher tea in southern Europe. And then I think like multiple sclerosis, which is autoimmune seas with a very high frequency in, in northern Europe, right? Normally Scandinavia, and it's remained a mystery. I mean, how can it be that you see the huge frequency high frequency in, in Scandinavia, particularly. And the and, of course, in parts of the US were Scandinavian settled back in the day. And, and there we can see those genetic variants are coming in with yamnaya. But quite surprisingly, they have been positively selected for, right. I mean, today, you look at multiple sclerosis, and you kind of think, okay, you know, what's the benefit here, right. And it's been positively selected for, and we can see, it originates with in yamnaya, it's been positively selected for around 5000 years ago, when m yamnaya. emerge, or shortly before that, and then it's getting positively selected for again, when they enter Europe. Right. And, and there had been some speculations that maybe this, these genetic variants that are giving increased risk of multiple sclerosis, also a giving people at increased protection against pathogens, bacteria and virus infections. And then when we look at, you know, 1000s of samples of the viruses and bacteria, very interestingly, we can see that the zoonotic pathogens, those that are jumping from animals to humans, right, the ones that we are fighting today, basically, and also in historical times, they seems to really emerge in the pontic steppe area. And they get to huge you see a huge explosion around 5000 years ago,

Nick Jikomes 56:54

I see. So the so I guess the idea here basically is, people were domesticating animals, we were living in close proximity to those animals. We started to get diseases from those animals, and then selection favorite people with genes to do with how our immune systems functioned. They were presumably genes that made our immune systems better at handling those zoonotic pathogens, but also left us vulnerable to things like autoimmunity.

Eske Willerslev 57:21

Exactly, because, because then the kind of the interpretation here is, of course, that, well, you know, to have such an overactive immune system is a benefit when you are, you know, when you're exposed to all these pathogens, right. But then, of course, in modern times where, you know, we are raised a lot of these pathogens, right, then you are standing back with an overactive immune system that then starts attacking you, right? Because of hydrogen, right, extreme hydrogen. But in back in the day, when you had all these pathogens around, it was it has been a benefit. And it's kind of noteworthy, I think, that if, if, if there hadn't been people like that, right, that had these variants, you and I probably wouldn't have been here today. So you can say we should actually be grateful for for the people who are carrying it today, and of course, are struggling with it. But they are really the reason why the rest of us has a place in this world today.

Nick Jikomes 58:29

You know, we mentioned some of those metabolic adaptations before. So depending on whether you're talking about having an ancestry that involves more of the hunter gatherers versus more of the Neolithic farmers versus more of the pastoralists from the, from the other regions, these people had different lifestyles, they had different types of food that they started to adapt to. So when you think about things like carbohydrates and different fatty acids and dairy and stuff, and you think about some of the prevalence of metabolic disease today and how it differs across different populations, how do you start to think about present day metabolic disease? Are certain people more susceptible to things like diabetes because they have a certain ancestry that's mismatched to the diet that they're eating today?

Eske Willerslev 59:13

Yes, I think that's exactly right. And the you can see, because farming and the farming lifestyle is the is the lifestyle that kind of get got you know, distributed across the world, right. Then a you can say, depending on when your ancestors underwent these, this change in lifestyle, actually influence you can say the chance of you getting you, right, because, I mean if you see when I've been visiting and work together with operating the Australians, for example, I mean, they are when you go to some of the communities is in Australia, I mean, we're talking two thirds, up to two thirds of the village has diabetes type two, one, and going into tiny dialysis and stuff. And these guys, the ancestors of these guys were exposed to this farming lifestyle may be, you know, 100 150 years ago, right? So there's obviously be no time no chance of any genetic adaptations, right? Yeah,

Nick Jikomes 1:00:28

they're just not they're not, they don't have the physiology that can handle a high grain base to dissect

Eske Willerslev 1:00:33

exactly this enormous amount of carbohydrate. And I think I even read some papers where, you know, that some of these people that are suffering from from diabetes type two, if you if they then you know, change the diet into Bush food and you know, then in some cases, you know, that the PD stops, right. So by while in, in Europe, obviously, I mean, they are we have had 1000s of years, right, we are not to adapt, we are not fully adapted. I mean, I mean, it's a very short time span, we have been farmers are having a farmer died compared to the timespan we have been hunter gatherers, right? I mean, it's hundreds of 1000s of years, we have, we have one on the gallery, but we are partly adapted, right, we are more adapted, if you want to this type of lifestyle. So it really you can see your ancestry in that regard, actually influence you know, your your, your, your health state, if you want or your chance, if you want off of being healthy or unhealthy. A given that the type of food you eating today is is an advanced form of farming, right?

Nick Jikomes 1:01:55

So is it fair to say, in some sense, all of us everywhere in terms of our metabolism in terms of our physiology, we are all hunter gatherers, because for most of human evolution, that's what people always were. And then certain people from certain lineages have partial adaptations to a more agricultural based lifestyle, but probably not come what we would call complete adaptations, because farming is so new, even for the people who are descended from farmers. That's exactly right. Yeah, so yeah. So yeah, a lot of our a lot of our modern metabolic problems have to do with the fact that that firming, adaptation is incomplete. And it's only in certain lineages, some, some people don't come from those lineages at all. No,

Eske Willerslev 1:02:45

exactly. So you see it also, right. I mean, many, many of the groups around the world that has these huge, elevated risks of diabetes type two, a very often, you know, people that were undergoing this transition very late in history, right. And you also see those among some Native American groups, for example. And, and so, I mean, people we used to learn in school, that the farming the agricultural revolution was the, the the revolution that created civilization, and all the good things in life, you know, we are, we are blessed with today, right. But another way to look at it, I would say is that, that the transition from hunter gatherer into farming also created a lot of the problems we have today. I mean, both in terms of course of lifestyle diseases, as we just discussed, but also in terms of the pathogen pressures, right? We see infectious diseases all the time, also in the in the galleries, but we don't see any evidence of these huge kinds of epidemics, they are first emerging, you know, when when you see this change in lifestyle, right? So so a lot of you can say, the bad things that people have suffering from historically as well as today are really a result of the farming lifestyle. And people could also say that the enormous population increase we have seen, you know, in the world is ultimately also a result of

Nick Jikomes 1:04:31

one so so on the topic of genes related to nervous system function and behavior. So we talked about Europeans, all Europeans is being comprised of some combination of these pastoralists who are tall and sturdy people who could dairy and had domesticated animals, the hunter gatherers that were leading a traditional hunter gatherer lifestyle, and then the Neolithic farmers who were some of the earliest farmers so all Europeans today are some sort of genetic combination of those three groups, and the exact balance differs from, you know, based on your personal ancestry, in terms of another way that those groups differ beyond diet is social structure, population density, the way they would have interacted with each other, I would imagine that each of those groups, right, you're living with a different number of people, the culture is structured differently based on you know, farming versus hunting and gathering versus raising animals out on the grasslands. Is there any evidence that the nervous systems follow different evolutionary paths that maybe certain personality types or certain disorders were more or less common in these different groups?

Eske Willerslev 1:05:38

Yeah, it's a good question. We don't know, we actually don't know, I would say, I mean, what we can see a, where we get some glimpse of some of this stuff. For example, if you look at, at the genetic genetic variants that today, in your, in Europeans in Northern Europeans give out higher risk of schizophrenia, for example. There we see higher frequencies in in the Viking period than what we see today. A, and the what to make out of that is, is is very hot. You know, it's, you know, if you kind of, I guess, the first thing when we saw it, that stroke, because you're talking about these circles in the bike, that the baby that was the ones or whatever, but we don't really know, and, and we have a very, I wouldn't say we have any, any good grip of, of, of how, you know, this is working out. I mean, one thing, which I think is striking is that, that when you look at an early anatomically modern humans hours pictures, and you take those a few, it's quite rare, but sometimes we find, you know, you know, skeletons that are, you know, 30,000, close to 30,000 years old, where you'll find multiple individuals, right? From the same site. So we did some years back, one called some gear in Russia, which is one of these around 30,000 years, they have all kinds of, you know, cultural ornaments and all kinds of stuff. And people, when, when traditional physical anthropologist had looked at these bones, they kind of said, well, it's a typical evidence of inbreeding, right? It's a small population, they don't can't find mates that breeding with each other. And inbred, and they one of them had an amulet of a human bone. And they said, Well, this is a neon totaal. They killed you know, it's an amulet and the, the humans that are lying hit to hit our close family members, and so forth. And when we did the genetic testing, all of this was wrong, right. So so it turned out that they are not closely related. Yes, they're coming from a very small population size, effective population size, they're very small group of peoples. But they're not inbred. And they're not closely bladed family members. And by the way, their so called Neanderthal bone actually turned out to be one of the persons ancestors that they were carrying, and not in the abdomen. And what is interesting about this, when you talk about the behavior to go back to the behaviors, what it tells us is that these early on the gallery's, besides being living in small groups may be, you know, Max 20 people by less very often less than that, they still avoid inbreeding. So they still have, you can see a behavior where they're going out finding mates, you mates,

Nick Jikomes 1:09:03

they have probably some kind of cultural taboo that

Eske Willerslev 1:09:05

they had exactly those some kinds of cultural taboo, right. But if you look at the Neanderthal genomes that has been sequenced, so far, which all laid down the tiles, right, they are incredibly inbred.

Nick Jikomes 1:09:19

Ultimately inbred, which I guess would mean either they never developed those kinds of cultural norms, or those late Neanderthals had no other choice.

Eske Willerslev 1:09:29

Exactly. So that's exactly the question, right? Why are they remaining inbred? Is it because they had no other choice? But it could also be and this is speculation from my end, but nevertheless, it could be that it's one of the key behavioral differences between Neanderthals and modern humans, because you can say in terms of survival, if you're relatively if you are, have a reasonable population size right. Then in terms of vital I mean, if you just met randomly, whoever you meet, meet with, you know, your family member you meet with somebody you meet you meet with everybody. Right? I mean, if you are a reasonable amount of people on the landscape, well, you will survive, right? Because some some of those children will be okay. Right? Some of them that won't, won't be very good because of inbreeding depression. But but as when you become very few people on the landscape, right? Then, of course, having this strategy of how to go out and get mates becomes incredibly important. And even historically, from modern human hunter gatherer societies, I mean, from the from America, from Australia and other places, you see the strategies to avoid inbreeding, right? I mean, if you think about the plains tribes, for example, right, they were also living in, in, in relatively small family groups, right most of the year, and then once a year, they are meeting these huge gatherings, right, where they are exchanging wives and mates, right, and then they are spreading out again. And, and so maybe it is a behavioral difference. And now I'm against big leading, but but if you look at these early modern humans, I mean, they have very strong cultural expressions, right? They have beats, all kinds of arguments saying we are us, you are somebody else, right? By to the best of my knowledge, this has never been found with the totals over find this kind of expression. That That kind of tells you where we are relative to another group, right? So it might be one of the key differences between the two.

Nick Jikomes 1:11:54

Another thing that I thought was so so I want to go back to something we mentioned earlier. So you mentioned earlier that when you looked at the skeletons of Neolithic farmers, as compared to say, the pastoralists, the skeletons were less impressive, they were more sickly looking, less robust. But we also mentioned that evolution is about how many ancestors you leave, or how many children you leave behind, not about how literally big and strong you are, if you know, if you could have a lot of babies without being big and strong and robust. You're gonna have a lot of babies. And that's, that's all evolution really cares about. Do we know anything about whether farming created, say, large food surpluses that just enabled people to have more children? Were they having more children? Do we know that for sure that

Eske Willerslev 1:12:41

we don't know that for sure. But that's the assumption. Right? The assumption is that you can see farming give you a more stable food source, right, that that you are less prone, you know, to, to kind of have fluctuations, right? I mean, of course, even for farming, there's good years and bad years. But the idea is that you would have Yes, have the right to have a more stable food source. Whether this is the only reason or the reason it's hard to say. I mean, one of the things we're trying to figure out, I can't come up with a definite answer yet. But we also trying to understand whether whether you can see, could it be that the farmers were just more fertile? I mean, that they genetically speaking, got more kids, I mean, than the farmers, right? We are the hunter gatherers, we don't know. And it's one of the things that would be very interested, interesting to understand, you know, but the general kind of assumption is, you know, it's it's the stability of the food production. But there's a lot of these basic assumptions where I think we have learned over the years that we have to be very careful. Because I mean, if you take we just talked earlier about the pathogens, for example, right? And you rightfully said, Well, the idea is, well, we were living with we domesticated animals, and because we were living close to the animals, this is why you know, the pathogen start jumping from animals to humans, right. And that has been the general notion for many years. But when we actually look at the data, right, what we can see is that we first really see this evidence of this happening around 6500 years ago. And, and farming started, you know, well, 10 12,000 years ago. Yeah. So so it's clear that I'm not saying that they've never jumped a pathogen from an animal to a human before 6500 years ago. But what I'm saying is, it didn't become common, right. Yeah. Under 500 years ago, because

Nick Jikomes 1:15:01

therefore, yeah, it wasn't common enough that you needed very strong selective,

Eske Willerslev 1:15:05

so. Exactly, exactly. So and it's only 5000 years ago, where we see this massive explosion, right in the pontic step of these types of of pathogens. So in other words, the explanation is seems not to be as simple as simply, okay, we have domesticated some animals, right now

Nick Jikomes 1:15:26

they are jumping, then something else changed in addition to that, exactly.

Eske Willerslev 1:15:29

Right. So there's something in the lifestyle, if you can say, of the, of the step people have these prongs, stiff May? Or

Nick Jikomes 1:15:41

may, perhaps they domesticated different animals and new types of animals? Who knows?

Eske Willerslev 1:15:45

Well, I mean, it should be kind of the same, right? But maybe they maybe they lived with the animals in a different way. Yeah, they were, you know, sleeping on top of them, or next to them, or whatever, or it was the show number. I mean, the numbers, the Hertz was just much greater. And, and it's, but it's just an example of one of these things where you can see there has been no explanation for, I mean, decades, right, that everybody seems to because it's kind of like, right, it's logic, with the, with the staple food source, right? Everybody buys into it and say, Okay, well, this is probably how it was. But then when we actually start getting some of the evidence, you know, the story is not just as simple as what we kind of assumed, and therefore, I'm a bit hesitant to say, with the farmers, you know, well, this was the reason right? It was because they got stable food sources. Yes, it might be. But there might have been other things at play here as well.

Nick Jikomes 1:16:49

Another thing that's interesting that I think you've you've, you've seen some interesting patterns with is when I think about Neolithic farmers, for example, I think about okay, farming means food surplus means more people. So you've got people living in proximity to more animals. And that with that comes the possibility of intestinal parasites, other infections, more people, which means another route for infections, because higher population density means easier transmission, but also more people means more potential mating opportunities, and with that sexually transmitted disease, and you've seen some interesting patterns in in your data, what have you noticed there when it comes to intestinal parasites and diseases and STDs? Yeah.

Eske Willerslev 1:17:36

I mean, it was a huge, I mean, generally, the general notion was that real, you can see epidemics in terms of you can see real pathogenic epidemics first occurred, you know, around the medieval times, right, that was the general notion that you had the black death. And, you know, that is this infections, you know, and and, and it was, it was really based on one Britain breakouts, and then the assumption that you needed fairly, as you said, yourself fairly dense populations, right for for pathogens to spread and epidemic man up. And then basically, by chance, that's when we discovered you know, that that the teeth are carrying, you know, these infectious diseases, right. We could see that during the Bronx aids, right. 5000 years ago, you had a massive plague epidemic, right? I mean, we had 10%, around 10% Of all the skeletons we looked at were infected by pestis, right with the bacteria that greats like so. So you can see it's, it's, it seemed and now we even have evidence of plagues happening earlier than that, right with the farmers with the farmers, there's also coming some some plague epidemics. So, so, you can say the, the whole the whole story of disease and and spread of disease is has been important way earlier than what we thought and has probably been a major driver of many of these migrations that we see you know,

Nick Jikomes 1:19:25

happening. I mean, you mean people probably did a lot of moving to get away from disease and things like to get away right.

Eske Willerslev 1:19:31

And also you had almost improperly almost entire populations dying out locally right. Meaning are they dying out new land becomes available, you know, other people are getting into this and this becomes this. You can say particularly during the Bronze Age and after the Bronze Age becomes this huge melting pot, right? Where where people are moving, you know, east, west, south, north and east and creating, you can say a world where as I said in the beginning, you know that that the world we are a product of today genetically is very young. Right? I mean, it's something that was established very, very late in our history. So I think these I mean, in terms of, of you can say in the role of pathogens and diseases, a has been much more pronounced if you want earlier, even in prehistory than what we what we previously from. Yeah,

Nick Jikomes 1:20:34

that makes a lot of sense. You don't need to live in a city of millions of people for pathogens to spread easily. It's much. Yeah,

Eske Willerslev 1:20:41

yeah. It's, it seems to be your it also the way the spread, right. I mean, the general notion at the time was that the earth is type of plague was the plague that was spreading, you know, from by fleas, right, biting fleas that by humans. And what we could see is that the earliest form of plague and pest this is really the one that is spreading through saliva and blood directly from human to human bite and multi human. And then, but there's no fle, a, and then we can see in the round the meat bronzer is right there is some 3000 years ago, that's when the bacteria get the mutation that allows it to survive in the free God, right. So it blocks the God of the fleet, the fleet becomes more and more hungry. And then it's biting and, and spreading. So a lot of you can see the the assumptions we had about these diseases completely change, we could also see, you know, things like Hepatitis B, right, which is a sexually transmitted disease today, there's hundreds of 1000s, I believe, dying from it, millions being infected every year. You know, when we started this kind of work, there was people who believed Hepatitis B have only been present in Europe for the last five, 500 years, right? When we then started looking in the ancient skeletons, we find it almost 5000 years back in time, right. So and and when you then take these strains, and you look, you know, at how do they resemble presentation strains, it completely changes our conception of mutation rates, right. So all the mutation rates about these pathogens that people were working with was based on modern strains, right. But the modern strains only is a tiny, tiny subset of all the strains that has been in the past, if you add those, right, the whole mutation rate, it changes and, and it's really fascinating, because it gives you it gives you you can say it gives you really a roadmap in terms of what part of a pathogen of a given pathogen, what is the super variable Region, right, what is very conservative regions that could be target for vaccine development, it gives you a you can say it gives you actually a very strong indication of how these pathogens will mutate in the future, right? Because when you get the genomes, you know, these were the ones that back in the day, this combination of mutations was successful, right? This is was a successful pathogen. And if it's a mat, and therefore it becomes only a matter of time, when will these mutation reappear? Right? So you can start testing well to our vaccines actually, do they? Can they can they handle, you know, these mutations that were in the past and likely will reappear, etc. So it's quite useful.

Nick Jikomes 1:23:44

One of the things that characterizes modern day Europeans is the light skinned phenotype. When did that first emerge? How quickly did it spread? And what was it an actual what was the adaptation? It wasn't vitamin D related? Was it something else?

Eske Willerslev 1:23:58

Yeah, exactly. So it seems like it's coming. I mean, the hunter gatherers, as far as we can see, were very dark skinned and and had these blue grey eyes. And, you know, even when the firemen start moving up, they had lighter skin than those right and then you had of course, yamnaya, in the Bronx HMI are coming in also with light skin. And you can say the

Nick Jikomes 1:24:26

general notion that was how long ago remind X

Eske Willerslev 1:24:30

is so the farmers are start moving in and around 10,000 years ago and the yamnaya the Bronze Age of knights, five 5000 years. Okay. Right. So and you can see the general notion is that it's due to a vitamin D, right, that that you were basically better at producing vitamin D from, from sunlight. And the I guess there's some argument there in the sense that When you look at the skin color of the avatars from your robe, they also seem to have light skin. Right. So it's it's it's kind of an adaptation to that, but it's something that is coming very late in our, in our history. I mean,

Nick Jikomes 1:25:15

the first, the first year less than 10,000 years. Yeah, yeah.

Eske Willerslev 1:25:20

And for the most part, it's really within the last 5000. Right. So. So it's, it's, it's something which we haven't had for for a very long time.

Nick Jikomes 1:25:30

Yeah. So something like that. So I'm very morphological trait like that can spread in five to 10,000 years. We talked earlier about lactase persistence. That's, I mean, I think my interpretation of the lactase persistence phenotype is, we're almost watching even to this day, the spread of that, like it's still spreading through populations, it's only partially reached fixation. When you think about the time periods that you study 510 20 50,000 years ago, when you think about the rate of change that you've seen some of these selection events happen in? What does that tell you about sort of the general speed of evolution? Because I often I often get the impression that people think evolution is much slower than it actually is. And that, you know, we haven't been evolving for hundreds of 1000s of years and things like this.

Eske Willerslev 1:26:17

I mean, it varies, right? I mean, I don't think you can say that there's, you know, one speed or, I mean, it varies due to the selection pressure, right? I mean, so So how important is it? If you want for the, for your survival and reproduction, right body can go incredibly fast. And I'll give you an example of this, right? So we did a study, I had a PhD student who did a study on the, you can say, on on a group called the Pancho, from Southeast Asia, which is basically a group of people who live their entire life, on the ocean, or in the ocean, in the water, right. So they are known as incredible free divers, right? They're basically they can keep the, you know, can be on the water for a very long time, etc. And she wanted to investigate whether some of these adaptations were generic by a so not only physiological adaptations, but whether that was genetic adaptations. And the general notion is that this type of lifestyle only existed for 1000 years, right. And me and the other supervisor, basically said to her, Well, we think is a very risky project, I don't we don't think you will get anything out of it. Because 1000 years is way too little time for for selection to act on this right. And they will, she decided she wanted to carry it out anyways. And she first you measured the spleen size, which is where the blood red blood cells are stored, right, and they had like, 50% larger screen size than the ones living in the closest relative living on land. But then we saw massive selection on on, you know, genetic genetic variants involved in spleen size in the diving response, that when you get when we get water into our face, you know, our broad patients will retract our spleen will pump out and so forth, blood, red blood cells, etc. So we're in 1000 years, you know, this group at just been on top massive selection pressure, and then she she interviewed. So some of the old timers, right, have these punch people and asked, you know, how can it be, you know, what, I mean? How can you have such a selection pressure? And they told her in the old days, you know, when the baby was born, right, they basically took it through a rope underneath the boat, right and or begin. And, and some of them didn't survive, right. Some of them survive. Oh, wow. And and if this is true, I don't know what that's true. But of course, if this is true, it's a massive selection, right? It's just,

Nick Jikomes 1:29:11

there's nothing faster than that. Yeah. Oh,

Eske Willerslev 1:29:12

there's nothing faster than selection. Yeah, exactly. So in other words, I mean, selection can happen. And not only the selection, but also the spread, if you want the segregation, of the selected variants, right, that's important to see it's not only the selection, but also the segregation can happen incredibly fast. Right, in some cases, and, and so I think some of the lessons at least that I have taken home from our work and other people's work in this area, is that that, you know, first of all, you know, this idea of, for example, in European Europe, right, that you people say well, we are very special in this even people in my country, making these claims you know, we We, we are very distinct from everybody else, and we have our own culture and it all developed and, you know, forget about it, right? I mean, it's a very recent history, and we all share it, you know, and, and, and things like skin color and so forth doesn't matter. I mean, I used to, before I did this type of work, you know, when I saw somebody on the street that look different from me, I kind of thought, oh, they are very different from me. Today, I kind of, well, it's a close relative, you know, it's like, you know, it's like, it's like a closet, right? I'm eating advice. And he Yeah, so it's, it's, you know, we, we, because of this history, where we have moved around, mixed with each other splayed out again, you know, brought with us cultural changes, etc. I mean, we are one big family. That's, that's, that's clear. And the world we live in is very, is very Western, how

Nick Jikomes 1:31:00

like, how different? Like, how would I ask this, like, if I took, if we look looked at your genome or my genome, and we compare them to each other, and then we compare them to some of those early people that eventually gave rise to all Europeans from you know, 10s of 1000s of years ago? How different would each of us be genetically?

Eske Willerslev 1:31:21

We wouldn't be I mean, you and I would be very similar. Right? You and I would be extremely similar. And most likely, because when I'm looking at you, I mean, we are probably both Europeans, I guess, in originating from Europe. But but if you go back in time, you know, it actually changes quite substantially, right? Because, because if you take a hunter gatherer, you and I would be, you know, we would have some yamnaya in in us, we would have maybe some farmer and some hunter gatherer, right, and depending on where we are from, you know, let's say, if we both are from Northwestern Europe originally, well, we would have a lot of yamnaya. Right, less of the others. Why the the hunter gatherer back then right, have the hunter gatherer, right. So so yes, I mean, all humans on Earth today is quite similar. That's the first thing I want to say, right? We are very similar. But there would be a substantially more differences between me or you and one of these on the galleries, then that would be between the two of us.

Nick Jikomes 1:32:29

I see. That makes sense. And I'm trying to look for like an anchor point, or something that we can use as an analogy. So if I think about something like domestic dogs, right, so humans domesticated dogs, I don't even know how long ago that was probably in the last 10s of 1000s of years. Yeah,

Eske Willerslev 1:32:44

it's around probably. It's also hard to say, but I would say between 10 and 20, right, something like,

Nick Jikomes 1:32:53

so if you compare like a dog a domesticated dog to a wolf? Is that like, how does that distance compare to the people that came out of Eurasia that populated all of Europe? If we compare us to them? Is it like, is that different? Is it more or less?

Eske Willerslev 1:33:10

It's a really good question. I'm actually not sure in terms of the analysis how it would come out, but I would say that that if you look at I mean, if you kind of look at air at a tree right of of European populations, if you imagine that you know on top of all the branches right you have the present day Europeans right how they are related to each other. And these early people coming out of of of Africa, injuring you can say Europe etc, they would fall totally basal on on on on you can see on the chunk of the tree, right, I mean, so they would be clearly separate, right? From all of us today, right? So, so because so but but it's because you can say we are even within Europe, I mean, because we today a mixture of these three migration waves that came into Europe and had of course similarities to each other no doubt, I mean, generically, but still were distinct from each other, right? They were distinct from each other. They had lived in it in a reasonable amount of time in in in in some degree of isolation, right. And they are then distinct, they're coming together, blending with each other in different ways. So of course, the you can say these blended individuals that you and I a at the deriving from you know, a different from each of them that are non glinted. Right. Got it.

Nick Jikomes 1:35:02

So what? What are you guys working on? Like right now? What are some of the big projects that your group is looking into? What kind of questions are you asking? Yeah,

Eske Willerslev 1:35:10

I mean, we still, so we still try to understand a you can see the original cause of disease risk in particularly in Europeans. And the reason why we're focusing on Europeans is, you need this kind of a GPS data where you know, which genetic mutations are associated with what diseases this is, you can see based on modern day studies, and, and unfortunately, this has mainly been done on European populations. So it's very difficult to, to you can say, do the same thing, for example, for Native Americans or Aboriginal Australians or something like that. So that's, that's one area where we are, we are we are working and also understand how this disease risk and differences in disease risk are linked to the pathogens, right, the pathogen pressures, and, and lifestyle changes. But then we also, I mean, we are still working with the peopling of the Americas is also an area where, you know, this is where I did a lot of my early work, and we're still doing work with, with the different tribal communities in America. And then, you know, our new big thing, which we're putting a lot of energy into, is to take these ancient genomes of the past but retrieved mainly from soil from sediment environmental samples of the past, where you get all the plants, animals, bacterias, et cetera. And, you know, using identifying which adaptations, both organismal adaptations, but also species adaptations to climatic change, right, that you can see, and then try to re introduce them into present day cropping systems, because we are facing a huge food security crisis. And it's only getting worse because of climate change is actually a real serious problem for humanity, right, because of climate change. It's, it's, we have a problem producing enough food. And it's because we have these monocultures of wheat and barley and rice, right? That that we have, we have selected for artificially a and there's very limited resilience to climatic changes. And we believe that nature carries the roadmap, you know, to how genetically adapt to these climate changes, because obviously, nature has gone through this before, right? There's been many climate changes before. So if we can read that roadmap from the past, and, and reintroduce them into some of these systems, our hope is that we can make more resilient but also more, you can see biodiverse cropping systems, right. So that's another area where we are putting a lot of emphasis right now,

Nick Jikomes 1:38:13

given given how cost effective genome sequencing has become, it's feasible for a lot of people to get their genome sequenced. Do you have your own genome sequenced? And are we at a point where you can get your own genome and then like, this?

Eske Willerslev 1:38:28

Obviously, I could do it, but I'm not. And it's, it's actually a deliberate choice from my internet's because, you know, as you know, there's all these kinds of companies ancestry.com and 23andme, is where you can put in your DNA, and then you can get an analysis done, and it will say something about your ancestry you are whatever, X percent from Spain or whatever it is, or Britain or, and, I mean, of course, you can say, I understand why people want to do this. And it's, it's, it's fun and interesting, and all that. And it's also in some, I guess, some ways, it's kind of, you can say, boosting the type of research we're doing into the past. And in fact, they are using a lot of our ancient genomes as well in there. They're downloading them and incorporating them into this, but the problem I see as the people very often use it as a means of identity. Right. So so, you know, you hear people saying, well, you know, Uncle Bob has some Finnish ancestry. Well, that explains why his like to drink or whatever they could see right. And I have seen you know, when when I've worked with native groups, indigenous groups around the world All right, that some of these groups are also using, you know, either genetics or blood quantum, for example, which is just another way of doing this, to kind of say, who could be a member or not a member of a community, right. And in my, so it's, again, you know, this about identity. But for me, personally, identity is who you believe you are, right? It's not nothing to do with your TNA record. It's, it's, you know, if you were born, that's a born and raised on a reservation somewhere in the US, right. And you believe, well, I've been born and raised, and I believe I am, you know, part of this community. Right, a and then somebody come in demands for a DNA test, and then they find out, well, you're not really part of this community, right? A is this, you know, what is identity identity is how you are raised how you are, who you believe you are, what community you are, have been part of. So. So therefore, I just feel that it's the wrong way of of using this type of data. Personally.

Nick Jikomes 1:41:21

What if you wanted to use it? Like, are we at a point where you could use it to? You know, we talked a lot about the different physiological and metabolic adaptations, that doesn't mean you just have, could you use it to help understand things like your metabolic disease risk, or make decisions around what to eat?

Eske Willerslev 1:41:38

Yeah, I think so. And, and it will be increasingly so right. I mean, it's still, I think, a challenge to use this type of data, for most cases, not all, but for many cases on an individual basis, right? It's, it's on a population base, right? Where you have a group of people and you say, Yes, as a group of people, you know, the one with more yamnaya has a higher chance of multiple sclerosis, etc. That works. But on for a single individual. In some cases, yes, it works, you know, the certain cancer genes and so forth. But, but in many cases, it's actually you can say, the predictive value on the individual level is actually not as good, right, as on the population level. So so it can be a bit dangerous to do it. But yes, I believe this is the direction things are going. And of course, as, as you can see, we understand more and more about you can say what the functions of the genome, I think this will increasingly be the case and people will have to also determine with themselves, right, do you want to know, or do you not want to know, right? Because that's the next question, right? I mean, you get some kind of probability, right? It's not like, you're told, Well, you will get the diabetes, or you will get this type of cancer, whatever, it's all a probability. And and do you really, do you want to live with that, and try to live accordingly to avoid it, but also bearing the burden of going around being nervous about getting something right, you might get or you might not get? A? Or will you rather, as we have done for the last 600,000 years, going around, and then see what's coming, right. And I guess it depends on on personality, and, and so forth. But yes, I think we are going in this direction. And And also, if you take, I think that that is a place where it can also help maybe is to the stigma stigmatize some of these things, right? If you take multiple sclerosis, for example, as I said to you earlier, right, the reason why you and I are here, most likely, because there was some of our ancestors that were carrying these mutations, right? And, yes, there are some people who should they are suffering if you're one, because the lifestyle is not the same, right? And we should be thankful for for these mutation was around, right. So it's another way to look at it than simply

Nick Jikomes 1:44:27

those diseases are, in some sense, an echo of a previous adaptation.

Eske Willerslev 1:44:30

Exactly, exactly. Right. And it gives us also a deeper understanding, I think of the diseases, right, so so it's not just something that is just coming around, for example, right? It's actually habit deep evolutionary roots, right? It's not something that you easily can just remove, but rather maybe you should start thinking of the disease in a different manner, maybe right where you are thinking about, well, it's all about getting the right balance between the immune system It's not about just hammering it down right to the top, it's about the balance, etcetera. I'm not a doctor. So I'm not trying to make a claim sheet about how it can treat stop people. But my basic, my basic standing is that the more we know about the underlying reason for any disease, right, and disease risk, I think we are in a better position to understand it, and therefore also treat it and deal with it. Right.

Nick Jikomes 1:45:32

Yeah, I mean, a lot of the disease or stuff that you've worked on, it sounds like sort of a general pattern was people started living in denser populations, both other human beings and animals, they domesticated, obviously, that facilitated the evolution of new infectious diseases and the spread of those diseases through these larger populations. And, in essence, some of our susceptibility to certain types of disease like autoimmune disease, we could sort of think of it as the immune system became more hyperactive in certain ways to deal with the higher density of infectious agents that were circulating. And a side effect of that in the present day is that in the absence of because we're cleaner, now we have more medicines, we, we have better hygiene. Those hyperactive immune systems so to speak, aren't they don't need to be hyperactive anymore. And then a side effect of that is something like MS or psoriasis, or whatever. He says, when we think about it, and that way we put an evolutionary context. What do you think about things like the the so called hygiene hypothesis?

Eske Willerslev 1:46:39

No. I think the hygiene, who pauses Is this about you know, many of the troubles we're dealing with in terms of immune ology immune system, diseases error, is simply because we become too clean if you want, right. And I think that the take home message here, which I think is important, is when we're talking about many of these, you can say variants that in a certain environment are creating some problems for us, right? In other environments, they are actually beneficial. Right? So it's not like where you're just saying, Oh, this is bad, right? Or, or this is good, right? It all depends on the context. Right? The same goes for, you know, the thing we talked about with the fat rich and and all that right, with the, you know, that the the change in food, right? So if if you can see if the hunter gatherer is was winning, or you're living as a hunter gatherer, right? I mean, you and I, that probably have some of these adaptations to a high carbohydrate food, right? Well, it would be nothing, right? It would not be worth anything in such an environment, right? It's only worth something because we actually living in a high carbohydrate, high tie, the type of diet we eating today, right? In our society. So in other words, it all depends on the context, right? It depends on where you are. And we all you can see, we are all a result of you can see our ancestral history, where something at some point in time and plays were actually beneficial in the past, right. And today may be it might be beneficial, or it might not be beneficial, right. But we all have this with us, we all Aryan that ancestry and delicacy of of, of our ancestors. And I would say if there's anything to me, it has kind of made me rethink if you want as an individual and as a human being is I don't know how it is in America but I always learned in school or we're told in school and at all by the way that you need to adapt it you need to adapt to it now you're going to school, you need to adapt and do what they say and you need to adapt to this and you need to adapt to that and so forth. But in reality, I think we should look at it differently, right? We all have this we all carrying this you can say genetic legacy with us and varies from one person to the next and from one population to the next. And it's really about finding the environment in my view that fits you are generic record, right. So you should go out and and try to find out you know, what is fitting me right? This what I'm carrying with me of good or bad or whatever, some is good in in the environment. I am now some is not so good. Maybe this environment is not the right for me. Maybe I should go somewhere else where I'm better suited. Right so.

Nick Jikomes 1:49:54

Well, this has been fascinating. I learned a lot and we only even you know we only had time to cover one chunk of human history. There's many other places we could have gone in time and in geography, you've done a lot of interesting work about Native Americans and the original humans to come into the Americas. So at some point, I would love to talk about that as well. But do you have any final thoughts or things you want to reiterate for people, but I think

Eske Willerslev 1:50:19

we have covered a lot of ground still. But you're right. I mean, we could continue. We've done a lot of work in Australia, a lot in America a lot in Southeast Asia a lot in Central Asia that we haven't really covered here. So well, if you want, we can just make another session at some point.

Nick Jikomes 1:50:37

All other paths. Yeah, I would love that. For

Eske Willerslev 1:50:42

you all again, say you are US based. Right. I guess the the peopling of the Americas would probably be something that some of your audience would find fascinating, I assume. But

Nick Jikomes 1:50:51

yeah, absolutely. And I still have to read some of those papers. So I don't know the details. Yeah. But thank you for your time. This was fascinating, and I really appreciate it. Okay,

Eske Willerslev 1:51:01

thank you. Have a good day. Bye.

Mind & Matter
Mind & Matter
Whether food, drugs or ideas, what you consume influences who you become. Learn directly from the best scientists & thinkers about how your body & mind react to what they're fed. New episodes weekly. Not medical advice.