Who are our ancestors and why does it matter?

Brian Cox: Hello, I'm Brian Cox and welcome to A Question of Science here in the auditorium of The Francis Crick Institute. A Question of Science is a series of discussions about the biggest scientific challenges we face today, from how to prevent the next pandemic to the future of treatments for Parkinson's and the challenges of climate change. In each episode, the panel of leading experts will tackle your questions. 

Today, we're exploring ancestry, ancient DNA, and how the past shaped who we are. The first studies of ancient DNA began in 1984 with the sequencing of an extinct type of zebra, known as a quagga. But subsequent advances in technology led to the sequencing of the Neanderthal genome in 2009. And since then, new techniques mean more and more ancient genomes are being analysed, generating extraordinary findings. 

Ancient DNA can tell us how humans evolved in response to changes in the environment, to viruses and bacteria, and burial sites tell us about ritual, family and relationships. But how does all this evidence relate to us now? To find out more, please welcome our panel of experts. 

Pooja Swali: Hi, I'm Dr. Pooja Swali. I am a research fellow at the University College of London studying ancient pathogens. 

Pontus Skoglund: I'm Pontus Skoglund, a group leader here at the Crick Institute and I lead our ancient DNA research. 

Adam Rutherford: I'm Dr. Adam Rutherford and I'm a lecturer in genetics and society also at UCL. 

Tom Booth: I'm Dr. Tom Booth. I'm a senior research scientist and archaeologist working on the thousand ancient genomes project at the Francis Crick Institute. 

Brian: And this is our panel. Before we begin, the episode, part of the title is, does it matter if we know who our ancestors are? So I'm wondering, and I'll come to you, Adam, because I know you have very strong opinions on this. Have you taken your own DNA test? 

Adam: Yeah, I have actually. I've done several commercial- you mean the ones where you buy the kit, you spit in a tube, you send it off and they send you some pretty pictures back? I have done most of those companies for professional reasons, obviously. And quite an interesting variance in responses. I mean, the most significant one was discovering that my dad is from the UK and my mother is Indian. I knew that 'cause I've met them. 

Brian: So it was accurate. 

Adam: It was largely accurate. 

Brian: But has anybody else done, you've all done them? 

Pooja: Yeah, I did mine and it came up with 100% Indian, which I kind of, again, worked out myself. But it is what it is. 

Brian: Pontus, have you taken a DNA test? 

Pontus: I have taken a DNA test. I mean, they've gotten better than what they were 10 years ago, but they focus on the past 100 years. And ancestry is much more than that. It's not just one time point. It's going to be different 100 years ago, 10,000 years ago and 100,000 years ago. Yeah, I'm Swedish. I don't know if that's... 

Tom: I did one as well and it's 100% Lancastrian. It was very specific with mine. 

Brian: Same as me actually. It's Oldham for generations. 

Tom: It distinguishes between Lancashire and Greater Manchester. So I imagine that's the divide between me and you. 

Adam: So basically you two, you're something like second or third cousins at best. 

Brian: I think I'm partially Yorkshire actually. 

Tom: Oh right. I can't sit on a panel with a Yorkshireman. 

Brian: But we're kind of joking about it. But in terms of the database that's being accumulated by those companies, is that useful for research in any way? 

Tom: It would be if anybody else could access it. All the DNA that we generate at the Francis Crick Institute, for instance, on publication gets made publicly available so people can use. But the DNA accumulated by private companies, it's under their auspices. 

Adam: The whole foundations of the Human Genome Project set up in the early 90s included open access for all data. And that was a thing that became enshrined at the real roots of this era that we are really enjoying. And so I don't think any of us really anticipated that commercial ancestry testing companies would become kind of the dominant force in databases. And I think that's unfortunate. 

Brian: And Pooja, we are talking primarily here about ancient DNA. Could you define what we mean by ancient DNA? 

Pooja: That's such a complicated question. It's like ‘historical DNA’ and ‘ancient DNA’. So historical is kind of referencing more museum specimens a lot of the time. So within the last hundred years or so. But then you have 'ancient', and this ancient DNA has these like distinct patterns where they're like fragmented and damaged. And so we say like if it has this damage, it's technically 'ancient'. But I still think there's not an actual definition because people work across so many different time points. So I work on a lot of historical DNA right now and I still see this damage pattern. But technically, it's not ancient because it's been specially preserved. 

Brian: So the word is not really to do with timescale. We're not saying if it's older than 200 years or something- 

Pooja: No. 

Brian: -then it's ancient. 

Tom: It's ancient if we have to use ancient DNA techniques to extract and sequence it, basically. I mean, that can apply to DNA up to even just sort of a few years old. If it's fragmented and damaged, then you have to use ancient DNA techniques. So technically- 

Pooja: I mean, technically, you could even have modern DNA that's been in a freezer, come out, been back in the freezer and also have that fragmentation. 

Tom: Exactly, if you set it on fire, that's a good way make it ancient DNA. 

Brian: What are the sources? So typically, where is that DNA coming from? 

Pooja: So when I was at the Crick, a lot of our material was skeletal remains. And then you have people who work on the human side or the ‘endogenous host’ side. So if you're working on a dog or a human skeleton, you could focus on the ear ossicles, which Tom can talk a lot about. But I specifically worked on the pathogen element. 

So we looked at teeth, which act as this time capsule, which is protected from the environmental DNA. And any pathogen that can get into your blood supply could potentially make its way into your dental pulp, which makes a fantastic source of these remnants of ancient pathogens. 

Brian: So that's coming primarily from DNA that's in, like a virus, basically, that's in there. So it's those physical structures. 

Pooja: If it's a bacteria and it's decomposed and managed to like bind itself into the tooth, so it's still fragmented, but we have that like chance to kind of take it out from the tooth. 

Pontus: Yeah, and so maybe 15 years ago, people were sceptical. I mean, basically didn't believe that it would be possible to study ancient human DNA in a serious way because of the problem of contamination. So there's contamination just by people talking in a room, all these kinds of things. 

But now we have, I would say, really good ways to make sure that data is not contaminated. What used to be a completely sort of catastrophic problem we can now deal with if we do things right. 

Brian: And other than teeth, are there any particular bones or any particular, if you have human remains, let's say buried, is there any particular place you look? 

Adam: There's a particularly hard bone behind the back of the ear, which is part of the skull called the petrous. And it's called the petrous because it's hard and that's the same derivation as the word rock in Latin. 

So when archaeologists are digging around, you find a nice intact skull looking for whether the petrous is there. But potentially for many bones, like the first Neanderthal genome was taken from the humerus, which is the upper arm bone. So it's all very dependent on how well the specimen is preserved, how the person died or whatever organism you're looking at. 

The temperature, so colder, drier is better than hot and wet, which is a big problem, actually, for those of us interested in deep human evolution, because it means it's very hard to get DNA out of human remains from Africa. 

Brian: Can you give us a sense of how much more difficult it is to sequence DNA from, let's say, as you said, the Neanderthal DNA? Because it's not long ago, is it? When was the Human Genome Project? I mean, the first complete genome was 20 years ago. 

Adam: 2000 

Brian: Yeah, so 25 years ago. So how much more difficult is it? How much better did we have to get to open up this science? 

Tom: Ancient DNA is fragmented into short fragments. You think of DNA as being a sequence of letters A, C, T and G. And there's 3 billion of those letters in the human genome that all gets fragmented into lengths of DNA that are around 35, on average, 35 base pairs long, so 35 of those letters. 

So a lot of the ancient DNA techniques that we utilise in the lab are essentially optimised for fetching those particular sequences that are of that length. The other main thing that's happened is the advent of next generation sequencing, this high throughput sequencing, which means that the cost of sequencing has plummeted spectacularly compared to what it was before. The richness of the data allows us to look at ancient samples in much more detail, but it also allows us to do what Pontus was saying and identify and control for contamination. 

Because every sample that we look at is contaminated, it's impossible for it not to be. If you think of archaeological samples, they've been handled repeatedly, they've been lying in the ground for hundreds of years, there's going to be some human contamination in there. So the question is often then, how good is the DNA from that organism in that it's good enough that it doesn't really matter about contamination, 'cause the contamination is such a small part of the overall sequencing. 

So when we sequence the DNA, we're mostly getting back the DNA from the organism that we're interested in and not the little bit of contamination from the people who've been getting the grubbing mitts all over it. 

Pooja: And this isn't bragging, but at the Crick, we have this one sample that's coming out very soon, and just this one individual was sequenced to 8 billion reads. It's a lot of data we're managing to get for not that much. In the grand scheme of money, in the grand scheme, it would have been quite expensive, but we've got so much data just from this one tooth. 

And the most incredible thing in this process is that once you sample that tooth, you turn it into what we refer to as 'libraries', and these are immortalised, like we will have them forever. We just go back to that sample and we re-sequence it, so we'll never run out. 

Brian: Yeah, and I don't want to be too technical a question, but so briefly, what's the main challenge? Is it the technology itself, the sequencing technology, or is it the data analysis? 

Pooja: It's everything. Yeah, it's everything. So Tom said like majority, like depends on your actual element that you're sampling. So we said ear ossicles are fantastic for preservation, but some of the teeth I'm looking at, I'm looking at like 5% of it might be endogenous, and then even 1% of that is the actual pathogen. And 70% of it is not even contamination, it's 'unclassified DNA'. So we can't even say what it is because there's no modern reference genome that's close enough to it. So yeah, it's really, really small percentages. 

Pontus: It's the dark matter of a human being. 

Pooja: Yeah. 

Brian: I should just say, to be clear, so we're talking about two things here. So your primary interest is pathogens, and we're also talking about the DNA of the, in this case, the human or the individual. 

Tom: Yeah, so that's why we target different parts of the skeleton depending on what we're interested in. As Adam says, if we were looking for the human DNA, we target this petrous portion of the temporal bone, which surrounds your ear canal inside your head. We're also increasingly targeting these what are called auditory ossicles, which are these three tiny bones in each ear. And they're the malleus, the incus, and the stapes. They're these tiny little bones that are around, well, the smallest is maybe about three milligrams. So a milligram being a thousandth of a gram, the largest being about 30 milligrams. 

And those bones, we only need one of those little tiny bones to get from an archaeological skeleton, and that will give us the best quality genomic data that we're going to get from that skeleton. And so we use those to target specifically the human sequences, and they're so much easier to process because we don't have to drill anything. 

We just take the ossicle and we give it to the robots that we have at the Crick, and I think that's how it works. I don't work in the lab. So we give it to the robots, the robots do the liquid, just process it, and then data comes out the other end, and then that's processed by the bioinformaticians. 

Brian: You sound like a particle physicist. 

Tom: The lab techs are going to kill me. 

Brian: Well, thank you. Wonderful introduction. So now it's time for the first question from the audience. 

Debbie Wilkinson: Hi, I'm Debbie Wilkinson, and my question is, what does our ancestry tell us about ourselves as individuals? 

Adam: The short answer is, I think, not very much. But in reference to what Pontus was saying a bit earlier, it really depends what you mean by ancestors, because our ancestors, the further back you go in time, effectively involves everyone on Earth. The way our family trees spread out from us is that everyone in history has had two parents. That's a fairly standard fact, possible exception of Jesus. That's a joke. 

What that means is your family tree, in theory, branches out, and the number of ancestors you have doubles every generation back. Now, that cannot work in perpetuity, because if you go back, say, 40 generations, which is about 1,000 years, then you'll have 1 trillion ancestors, which is 10 times more than the number of humans that have ever existed. So what we know, actually, is that family trees branch out from you, but then they begin to collapse in on themselves. Pedigrees collapse.And you have 1 trillion positions on your family tree, but not 1 trillion individuals. 

So the question then becomes, well, when do you mean when you're talking about your ancestors? And who are they? How do you want to limit that question? The fact is that your genetic relatedness with your actual ancestors drops off a cliff after a few generations. DNA is incredibly good at identifying first-degree relatives, brothers and sisters and parents and first cousins. But the fact of the matter is, because of the way families work, because of the way genealogy works, pretty much everyone in this room is a fifth cousin or a sixth cousin or something like that. We've already established that Tom and Brian may be dangerously inbred. 

Brian: So I think you are related to William the Conqueror though, aren't you? 

Adam: I am directly descended from William the Conqueror, and I have demonstrated this both mathematically and genealogically, and what that means is that everyone in Europe is as well. So I can claim no special rights there. 

Brian: Our next question is about how our ancestors spread around the world. 

Adrian Baker: I'm Adrian Baker. My question is, how can the study of ancient DNA help us understand the environmental and climatic factors that influence the migration patterns of early humans? And are there any significant shifts in these patterns that could have been significant in human history? 

Pontus: Yeah, I think the best example I think we know of, that I would say, is about 10,000 years ago, the last ice age ended really, at least the climate became much warmer. And what happened in our part of the world is that people started using, or our corner of the world, in the Near East, people started using agriculture, farming, having animals. And that spread across Europe, all the way to remote, sort of peripheral places like Britain. Rolling the tape forward about 5,000 years to, for example, the sort of people that built Stonehenge or started building Stonehenge. They would trace about 80% of their ancestry to the Near East. And that's something we can only know, it's an interesting sort of thing about history, we can only know it by studying ancient DNA and studying ancestors. 

Adam: Yeah, a really basic example that answers the gentleman's question was that we teach at GCSE level in this country, which is that malaria is, we can see genetic patterns, which reflect people whose ancestry exists in malarial zones, because sickle cell disease and sickle cell trait, which is still a serious disease, but not as serious as the disease itself, almost perfectly maps onto places where malaria has been endemic. And that is reflected in the migration of people around the world who carry sickle cell trait and sickle cell disease. 

So the genome represents our biogeographical history in that regard. And that's why it's been so... The revolution that we're in in science is as a result of getting all the genomes out of people who've been dead for hundreds, thousands, tens of thousands of years. 

Tom: From an archaeological perspective, we've always had a problem with identifying migrations generally, because we had to use things like changes in funerary practices, changing technology, changing pottery typology, just kind of try to infer when new people might have arrived with new ways of doing things. 

And what the ancient DNA allows us to do is actually identify because we see the ancestry change that occurs when people migrate. And then almost every ancient migration, there's been posited some idea that it might be linked to climate change. So for instance, Pontus was talking about the migration of early farming societies across Europe with an origin in Anatolia. So when they arrive in sort of what's now northern France, there's a 1,000 year gap between them arriving there and then coming over to Britain. So they'd be able to see the cliffs of Dover from the coast, but yet didn't make that final push over. 

And one of the reasons for that was that it seems to coincide potentially with a slightly climate amelioration, which meant that Britain became more sort of productive for farming, and that that's what eventually allowed them to move over and establish settlements in Britain. So always, it could be linked back to these changes in some ways. 

Brian: When you start to see groups of humans living in closer proximity, does that affect the way that disease operates in the population? 

Pooja: Yeah, so this time that Pontus and Tom have both spoke about this Neolithic, it's what we call the 'Neolithic transition'. It's this time period where people are living in this closer together in these large settlements, and we see the domestication of a lot of animals. And by being in closer proximity to animals and each other, there's more opportunity for these host jumps to occur. 

And so there's some research done, and Tom and Pontus can mention this as well, that they're looking at how many pathogens have had this transition. And one of the really interesting ones, the ones that I worked on when I was here at the Crick, was Yersinia pestis, specifically this lineage that's associated to this time, the late Neolithic, early Bronze Age. And we found the earliest Neolithic Bronze Age plague in Britain. And it's a very interesting one, because you can kind of do this phylogenetic tree. So we look at how the pathogens are related to each other. And we see that this one was very special. And it links us all the way from Britain to Russia, this large span across 2,000 years. And it's associated with these large migrations and these settlements at this time period. 

Tom: It's interesting thinking about the human responses to plague and the societal responses to pandemics that we're all keenly aware of in this room from recent years. So the site that Pooja found the plague on, it was what's called a Bronze Age cairn. So 4,000 years old, these funerary monuments were being built that were made of piles of stones, and then bodies were inserted into the cairn. 

So initially, one man was inserted into this little cairn. And then a few years later, a bigger cairn was built that cut into his cairn. I'm not sure how we felt about that. And his granddaughter was placed inside the cairn, along with two women who were unrelated to her or the original man. And Pooja found that it was the granddaughter that had had plague. And so potentially, there's an interpretation of the site that says that these cairns aren't where everyone's being buried. They're built at certain times for certain people for very specific reasons. 

But there's a perspective on this, which says that the building of this cairn was in response to some local pandemic, which killed this person who was potentially an important descendant of this man that had been buried there before. And it was potentially in response to this pandemic, which triggered the building of this sort of grand cairn where this woman was built. So being able to see these things allows us to understand the archaeology and get a sense of, again, these community responses to disease and epidemics and things in times when there was no writing - prehistoric. 

Brian: I'd just like to pick up because it's related to what we've been talking about. It's from Graham Swindell, who can't be here this afternoon. But he had a two part question, which is to Pooja initially, which is, if our ancestors suffered from pandemics, we've just spoken, established that they did, can it be seen specifically in their DNA? And the follow up was, if so, is there evidence of pandemics, diseases experienced by them, that modern humans have not yet encountered? 

Pooja: So are there pathogens that have existed in prehistory that we have not found, pretty much? Well, it's quite a little bit difficult to say, because we're completely based on our modern datasets and what's present today, and if we have the data for it. So it's a game of like matching those ancient samples to what's closely related today. 

Brian: So you saw something that was radically different, you wouldn't necessarily know what it is. 

Pooja: Yeah, if it's radically different, then no, but pathogens don't evolve like, at least bacteria, they don't evolve as fast as... they evolve fast, but they're not that fast. Like TB is a very, very slowly evolving pathogen and same with Yersinia pestis. So we kind of use that information of the diversity that we have today. We look back and we say, is it close to this diverse kind of soup of pathogens? Is it close enough? And then when it is, we reconstruct that relatedness, like you do with humans, you reconstruct that relatedness between the pathogens. And then we see, oh, it sits actually a little bit further away, but it's still part of this tree. 

Brian: And Pontus, that question, do we see it in the DNA itself? 

Pontus: Yes and no, I would say. So we can see it over millennia, we can see selection on immunity genes, pinning them down to specific pandemics. So I'm talking about a thousand years, we can see it, but pandemics, they happen on a timescale more of years. And so we're going to need a lot of ancient individuals, a lot of genomes to really get the statistical power to do that. But I mean, that would be, I think, could be enormously powerful to pin down, how did evolution sort of solve this challenge of different pathogens in the past? 

Brian: So just to follow up for the non-experts, so you're looking for a gene, you know it's an immunity gene. So you're looking for an increase in the frequency of that particular gene? 

Pontus: Yes. And in fact, we want to be sort of going with an open mind. And so we have to look at millions of variants, each looking at their frequency and seeing if there's anything that's too rapidly evolving for just random fluctuations in our ancestry. 

Pooja: And if you go even further back, this is different to the immunity side, but if you go even further back, yeah, there's evidence of like, what would have been viruses integrating, 'retroviruses', we call them, integrating themselves into the genome as well, which is really cool. But this is before Homo sapiens, this is way further back like in our evolutionary history. 

Brian: So interesting that isn't it? I know we should go to the... what is the percentage? 

Adam: 8 to 10% of the human genome is made up of viruses that have infected our ancestors. 

Brian: So they've just randomly become inserted. 

Adam: Yeah, if you think about it, the Y chromosome is much less than that. So we're more, humans are more virus than we are men. 

Brian: With that, we'll go to the next question. 

Geraldine Cooper: Hello, I'm Geraldine Cooper from the charity Crohn's and Colitis UK. And my question is, there was huge excitement in the inflammatory bowel disease community when research at the Crick uncovered a pathway linking genetics to IBD. 

How much can our ancestors' DNA tell us about who's at risk of developing inflammatory diseases, which are so prevalent in modern times, and how to treat them? Could this hold the answers that we've been waiting for? Thank you. 

Pontus: This is work led by James Lee's group here at the Crick. And what they found is this mutation that would turn up or down the volume of a gene that's really important in inflammatory bowel disease. But then when they thought about the evolutionary history of this mutation, they could see that it was a million years old and found actually variable even in Neanderthals and their cousins. 

It made them think and look more harder. How could it still be around if it's so obviously detrimental in terms of contributing to IBD? How could it still be around? And they looked into it and they could see that on the flip side, it had an effect of protecting against acute bacterial infection. 

And this kind of balance, sort of trade-off between autoimmunity and bacterial defence or pathogen defence more broadly, might be a really important driver of these kinds of things. And they said that actually having this evolutionary perspective made them realise that they shouldn't, sort of with interventions, try to turn off the gene completely, but try to turn it down. 

Tom: And it's one of the things we're looking at ancient samples for as well. The flip side of these past pandemics that we see, for instance, the plague that Pooja was talking about, as we interact more with animals and as we live in more densely settlement, is that potentially our immune system becomes over-responsive to threats and that leads to autoimmune disorders. 

Pooja: And Adam mentioned earlier about sickle cell and malaria, but there's also other immunity towards malaria. And one of the interesting ones is this species, Plasmodium vivax, which is widespread across Southeast Asia and South America. But that immunity resides mostly in Africa towards a species that isn't actually there, which is very, very interesting in itself because it starts us to question, well, if we know the immune genes are here, maybe we can start to see, is there any relationship and correlation with pathogens over time in that region? 

Brian: So staying with the question of illness and disease, we've now got a question specifically about the plague. 

Janice Kinory: Hello, I'm Janice Kinory and my question is, theoretically, most modern people of European background should be descendants of people who survived the Black Death. Is it more likely that those who survived the outbreak had genes that helped protect them, or were they just really, really lucky? 

Brian: Pooja, just by way of context, where do we first see the earliest evidence of the Black Death? 

Pooja: So we have what we call the first plague pandemic, which was Justinianic around 500 to 700 AD. And then it kind of recedes, it disappears. So we don't know where it goes. And then you see this resurgence during about the 1300s. Then it recedes again. And then we don't see it until the 1800s and the Hong Kong plague. 

So we see these moments of it just disappearing. And we don't know where it's hiding. We assume it's gone back to a reservoir population. 

Brian: And this gets to the heart of the question. So in Europe, pretty much everyone was exposed to it. The question is, is there a genetic reason why some people survived? Has everyone got some kind of mutation? Or is it just luck? 

Tom: It's always got a mixture of both things. I mean, you could think of having the genetics to survive it is luck. But like all things, the mixture of genetics and environment - that you might have a genetic predisposition to getting seriously ill from Yersinia pestis. And the circumstances of your life mean that you don't catch it. 

Similarly, you might have someone who is really predisposed to it, but through chance, they don't get exposed to it in the same way. So you can't separate them out when thinking about these things. 

Brian: The next question is about the ethics of extracting DNA from our ancestors. 

Christine Hinton: Hello, I'm Christine Hinton. And my question is, do you have any ethical concerns about removing skeletons that have been buried in good faith by our ancestors? 

Tom: I mean, as a human osteologist, someone who studies human bones, ethics is a big part of what we're doing. We're always thinking about sort of the ethical implications of what we're doing. I have a coward's way out for this question in saying that most of the samples of human remains that we look at from this country for the project we're working on here, have come from archaeologists that are involved with commercial development. 

Someone wants to build a building as part of the planning regulations, they have to check whether there's any archaeology there. And if there is, they have to pay a commercial archaeology unit to dig it up, and that includes skeletons. So there's no way we could build the things that we needed without occasionally disturbing cemeteries, many of which people didn't know were there. 

But I think there's a broader point here, which is more about balancing our obligations to living people and to the dead. I mean, when we look at cemeteries, particularly Christian cemeteries, for instance, we can make a reasonable assumption about what that person wanted, or at least what that person's community wanted in terms of their dead. Remember, the dead don't bury themselves. 

And in some cases, we've go back to prehistory it's clearly not the case that everybody expected to stay in the ground forever. There's evidence of handling of human remains, of recirculation of human remains. So those are important points to bear in mind as well. But also, I mean, they can't really consent. If someone, for instance, who died in the Black Death pandemic, if we could go back and say, if we dig up your remains, we're going to learn more about this disease and more about how to respond to this disease in future to prevent further pandemics. 

Or on a more humanistic side, everything about your life will be forgotten unless we dig up your remains and analyse your bones. How would they respond to that? We have no idea. It's impossible to know. There's kind of an idea that you put a human body in the ground, the bones stay there in perpetuity. They will degrade eventually. So if we don't take the opportunity to get this information out of them while we can, there's no guarantee. We're essentially denying future generations the access to that information as well. 

So in that sense, the effort that we put in, to me, that's the ultimate form of honour to these people that we can give to them in the present day. So I think that ethically, the balance is towards trying to do as much as we can to understand people in the past. 

Brian: Adam. 

Adam: This is a huge question. And I think that it's really important to recognise that ethics, as always is the case in science and the law as well, follows the scientific and technological developments and often quite slowly. And I think timescale is a real issue on this. So for example, I co-supervise a student who's working on people who were buried within the last 500 years, found in a crypt and establishing who they were. We have historical records for some of them, which means they have living descendants. 

Now, the information that we can get from their DNA may be relevant to those living descendants. And so who has ownership of that? Do we have the right to expose that and publish those sorts of things when they are only four or five generations away from people who are alive today? 

And then there's a much deeper history, which is relevant to everywhere on earth where we're getting DNA out of people who died a long time ago. But I think no more so and no more importantly than in North America and particularly in the USA, where there have been some really problematic cases over the late 20th century and into the 21st century. The classic example, one of the most significant finds in understanding the people in the America is the discovery in the late 90s of a man who died 10,000 years ago in Washington state who became known as Kennewick Man or the Ancient One. 

And various people claimed he was not of indigenous American descent, but was in fact of European or white Western descent. And that was based on measurements of his skull. There was a white supremacist, Odinist cult from California who claimed that he was Norse in origin, which is obviously absurd. And what happened was that this got bounced back and forth through the courts for more than 10 years. I think it was resolved in 2014 or 2016, but eventually was sort of resolved and they managed to get DNA out of him. 

And guess what? He was indigenous American and he wasn't a Norse white supremacist or whatever the other people had claimed. Now it's one of the reasons because these people who died a long time ago become political pawns in very complex ethical discussions. And I accept a lot of what Tom just said, but our considerations about our ancestors are not going to be the same as for different groups around the world who have different traditions and different relationships to their ancestors. And nowhere is that more significant than in the Americas. 

And as a result of scientific colonialism and some extremely bad behaviour by scientists in the 20th century, on top of the extremely bad behaviour of European colonists in the Americas over the last 400 years, what that has resulted in effectively is that we know much less about the peopling of the Americas than we should do if we hadn't screwed up so many times by being bad at our jobs. 

Brian: Let's go further back in time now because we have a question about our early ancestors. 

Rebecca Hanley: I'm Rebecca Hanley and my question is, how does Neanderthal and/or Denisovan DNA express itself in modern humans? 

Pontus: We think that many people, particularly people that have non-African ancestry, there will be about 2% of their ancestry traces back to Neanderthals. So that's both about 2% of their genome. And if we think about it in ancestry, if we would go back 80,000 years, 2% of their ancestors would be Neanderthals. 

And so I think the question is more about the biology. And of course then, yes, if 2% of genes, mutations are from Neanderthals, they're going to affect roughly 2% or so of our biology. And there are some interesting cases such as possibly this mutation important in COVID resistance that probably came from Neanderthals. And we should expect that, right? If there are 2% of ancestry contributing to us today or to people today, it's going to affect biology. And that's also why it's important. 

Pooja: Denisovans have been in like Southeast Asia for way longer. And when they've introgressed into East Asians, you see these genes such as adaptation to like higher altitudes, which you see is still present in the East Asians, which is one of those things that like, this is how this is actually benefited. And then these are one of the rare examples that we can say, this is probably where it came from. But these are like one of those rare examples where we're like, okay, this is maybe that useful bit of DNA that we're getting from our ancestor cousins and stuff like this. 

Adam: Everything they've just said is brilliant and true and it's amazing science, but just we have to regard the Denisovans and the Neanderthals as our ancestors, because that is what they are, right? And there's a whole different programme that we could talk about what defines a species and I reject almost all of those. 

Brian: No biologist ever answered that when I've asked it. 

Adam: Well, that's because there isn't a good definition. But the thing is that if you don't refer to your grandfather as the person who shagged your grandmother, right? You're descended equally from both of those two people. 

Now, I know the proportions are different when we're talking about Denisovans and Neanderthals, but they are our ancestors. They're not cousins. They're people that your grandfather had sex with. So in a sense, it is interesting that we can see the pathway of individual genes from ancestral populations. And I think that that is top science. 

But it does reflect a sort of cultural obsession that we have with this is us and these are other people and the genes from them entered into our lineage. Denisovans are our lineage. Neanderthals are our lineage. They are our ancestors. They're not our cousins. Okay, next question, please. 

Kirsty Monaghan: Hello, I'm Kirsty Monaghan. And my question is, I'm often told my red hair has been passed down from my Scottish roots. How likely is that to be true? 

Tom: I think Adam should answer that because it annoys him so much. 

Adam: I'll do this quickly and maybe as a monologue. So red hairedness for the longest time has been associated with alleles, which is variations in genes, of a gene called MC1R. And about 17 or 18 different versions of that genes of which you have to have two copies in order to have red hair have been identified. 

The latest studies using UK Biobank data have indicated that most people who have two copies of red hair genes don't have red hair. We don't really understand how pigmentation works in hair as indeed we don't really understand how pigmentation works in skin or indeed eyes. However, the highest concentration of people with red hair are geographically isolated to Northwest Europe and the highest concentration within Northwest Europe is Scotland and Northern Ireland. So the answer is yes, but it's complicated. 

Brian: And we have one more question. We're almost running out of time, but Katie Downs, it's a fascinating question. And perhaps Pooja, we touched on this before maybe with diseases that are completely unknown to science. But the question is, how much of the unknown ancient DNA do you think is from an unknown species? 

Pooja: Oh, yeah, that's a good question. Because we know how we mentioned this like fragment length being really, really short. If it's less than 35, we get this issue where it will match to lots of different species. So the longer these stretches of DNA, the better it is that this won't match to basically everything that we've got sequenced. So we want those really, really long stretches. 

And there's loads and loads of samples that haven't been sequenced and people are still to this day finding these new species. And it's not just with pathogens where you kind of reconstruct that phylogenetic tree where you can see what it's closely related to, but they do these with animals. One of the oldest DNAs we have is a 2 million old bit of DNA from a mastodon in Greenland, which was incredible because they didn't even actually use the bone or any samples. They just went into the soil and managed to get these mitochondrial DNA, these little bits of DNA from a mastodon, which we didn't even have the genomes for. 

Pontus: Yeah, and I mean, it's a great resource to have this entire data set. So we sequence it all and sort of look at it with computational methods. And one thing we're really keen to do is to, by having many individuals, to really understand this in a better way. 

'Cause in one way, using DNA to track these pathogens as was done with COVID, right? It's only been available on the scale of maybe decades, but pandemics and epidemics, as we've talked about, are on a scale of millennia. So maybe by having good sample sizes of people that lived in the past, we can sort of follow also the sort of rise and fall in prevalence of these diseases to understand and predict it better. 

Adam: I think one of the best, most exciting stories in the last 20 years in a field which is undergoing this incredible constant revolution, it comes from comparing the DNA of the Denisovan girl with that of the known genomes of Neanderthals with the genomes of us. And establishing that there's DNA in the Denisovan genome which doesn't appear to have come from Neanderthal or from Homo sapiens. And that implies that there were ancestors of Denisovans which were from humans and we don't know what they were. 

So there's a phantom species present in ancient DNA. And maybe it is a species that we're aware of, that we have remains of, bones of, but we only know the existence of that species based on the DNA and not from who they actually were. And I think that's close to being indistinguishable from magic. 

Brian: We had one last question from Jason West. I don't know if Jason's here, but it was a great question we thought we could end on. So very briefly with this complex picture, you alluded to it there, even other species that may have fed into the human story. How important is it that we create a sense of our shared humanity? Does this science have a potential to do that? 

Adam: I think the answer to that is a very clear yes. I mean, the thing is that more than anything that genetics has shown in the second half of the 20th century and now into the 21st century is quite how closely related humans are. We've talked at the very beginning about the shared genealogy, that the entire population of Europe is the entire set of the ancestors of us all today. We have shown conclusively that the artificial divisions that we created in the 17th and 18th century based on physical characteristics such as skin colour and hair texture are not reflected as discrete groups in our genomes, which is the true metric of human similarity and difference. And so that's why we refer to race as a 'socially constructed' idea. It is not biologically meaningful. All of these things point in one direction, which is to our shared humanity. 

Yeah, and on that, it's not just genetics. We are very, very well connected. I mean, just even looking at this late Neolithic plague that stretched all the way from Britain to Russia, it's not just genetics, it's also human connections. We see with the late Neolithic, early Bronze Age, how that lineage, that pandemic could spread all the way from Britain to Russia. This is before planes, trains and cars. So we're always mixing what is very complex trade routes and sharing of information and culture and languages. And it doesn't just have to be this idea of we share genetics to feel this like human unity. 

I mean, yeah, it augments what we see at archaeological sites as well in some ways. We have this site in Poulton in Cheshire, which was a medieval cemetery, where we have phases of plague. There was a Black Death plague epidemic that went through this community more than once. And at one point, there was a burial of two children. We found out that those children probably died of plague and that they were brothers as well. So when you see those specific contexts and are able to use DNA to add to those specific stories of those individuals within these communities, that gives you sort of a very acute sense of these were human people in the past having the same reaction and having to respond in particular ways. And that's what the DNA can sometimes help with. 

Yeah, I mean, at least to me, I really get this sense of wonder and thinking about this different ancestry that ultimately connects us all and sort of a sense of vertigo, looking back these hundreds and thousands of generations into the past. I mean, very much shared humanity. But I would also say that, you know, if anyone is sitting and sort of don't believe what is said, Tom mentioned that all the data from ancient DNA in general is publicly available. And if you have a bit of coding experience, you can download it and ask those questions yourself, and that would be doing science. 

Well, thank you very much. Thank you to our panel, Dr. Pooja Swali, Professor Pontus Skoglund, Dr. Adam Rutherford and Dr. Tom Booth.