#1248 Carles Lalueza-Fox - Identity: What DNA Can Tell Us About Ourselves

00:00 Ricardo Lopes: Hello everyone. Welcome to a new episode of The Dissenter. I'm your host, as always, Ricardo Lops, and today I'm joined for a second time by Dr. Carlos Lueza Fox. He's director of the National, the Natural Science Museum in Barcelona, and today we're going to talk about his latest book, Identity, What DNA Can Tell Us About Ourselves. So, Dr. Lweza Fox, welcome back to the show. It's always a pleasure to talk with you.

00:29 Carles Lalueza-Fox: Yeah, it's a pleasure also, for me to be here with you.

00:33 Ricardo Lopes: OK, so, uh, let me ask you first, uh, what is identity from the perspective of genetics, because, of course, I mean in other sciences and other domains of knowledge like, I don't know, psychology, philosophy, and so on, perhaps people would have a particular understanding of what identity is, but from the perspective of genetics, how do you approach it?

01:01 Carles Lalueza-Fox: Um, YEAH, yeah, you're right. I would say that, uh, identity is usually, um, considered a set of traits that defines, uh, your own, uh, sense of belonging either as individual or as a member of a collective. And these traits can be, you know, a mixture of several things like social traits, and, you know, you can be rich and you can belong to the, to the rich community in your country or whenever you can speak a particular language, you can have a particular religion. So it's a set of Um, you know, some, some traits which are, um, cultural, but then, um, some of the traits that define identity in this broad sense, uh, at the same time, kind of, uh, um, difficult to define are root in perceptions of geography and, uh, place, let's say, no, so you have a particular identity because you belong to a group that has been In that, mm, you know, uh, particular place of the Earth during hundreds, some would say thousands of years, um, and, and this is something that clearly can have, um, a root in genetics and can be tested from genetics. And so the whole idea, although, you know, I would say genetics, um, Uh, has never been, um, concerned about defining identity in humans. It's clear to me that some of the traits that define, uh, identity can have this temporal dimension then that can be now explored from genetics, especially because we are. In a very special situation where we are able to retrieve genomes, thousands of genomes from the past, we are able to model pedigrees in millions of people, something that computationally was impossible to do just some years ago. And also we have this enormous forensics and ancestry databases. So the combination of all these. Uh, DEVELOPMENTS, which are some of them very recent, less than 10 years ago, is what, um, makes the possibility of linking, uh, notions of identity with genetics for the first time, I would say.

03:38 Ricardo Lopes: But I mean when we talk about identity, are there different levels of identity, or are we simply focusing, for example, on individual identity, or can we through genetics also talk about some other forms of collective identity, for example?

04:00 Carles Lalueza-Fox: Yes, uh, yeah, you are right. I think there are several levels and layers of identity, uh, in, in any situation, just talking about uh what I mentioned before, social, cultural identity, etc. uh, WE have this perception of ourselves as single individuals. Uh, BUT then at the same time, uh, we have this perception of, um, you know, uh, where do we belong, uh, beyond being single individuals, uh, because we are inserted in a social context, so, uh, we need to feel that. You know, we belong to a particular family, extended family, group, clan, nation, state, whenever. So there are kind of different levels of identity. The basic one is, I am myself and I am a person different from the rest of the persons. We'll see also that this is something that it has been debated also, uh, especially in cases where we have like uh copies around. Uh, BUT then there are collective level, um, of identity and some of these, uh, these, uh, higher levels can also be explored from genetics. So, uh, genetics can explore the individual level, uh, because we can have our genome sequenced and compared to genomes from other people either around us or from distant places. Um, BUT also genetics can have an, an, you know, an overview of the diversity within the collective identity we, uh, we belong, we belong to. So, identity has this kind of a strange perception, um, where it's not only important that we decide who we are, but also What happens with the rest of the people? How do they see us? I mean, they see us as a member of, of, of them like belonging to, um, to themselves or someone different, so, yeah.

06:14 Ricardo Lopes: But I mean when it comes to the different kinds of social identities that we might have, uh, do they have a correspondence at the level of genetics, because for example, we might have an uh family identity, we might have a community identity, we might have a national identity. And then there's also social categories like for example ethnicity. We also use concepts like race socially and we'll probably come back to race specifically later, but I mean I I just wanted to understand whether we should treat all social identities that. Use as having some basis in genetics or if at least some of them we sim we we should simply treat as being social identities as having a reality but simply in the realm of sociology, for example, and not so much in the realm of genetics or biology.

07:27 Carles Lalueza-Fox: No, no, it's, uh, yeah, it's obviously it's a very complex, uh, uh, interplay, and, and some of them are quite I would say closely linked to genetics. I would, I was thinking in the family level, but not, not even in the family level because for instance, you know, I have an aunt and I have an uncle, uh, but, uh, the only one who is, uh, my close family is my aunt because my uncle, you know, is the husband of my, uh, aunt, so they are family, uh, in a level that everyone will consider family like, uh, associated to kinship and, and, and. Uh, GENETICS, but, uh, you know, some of my family, uh, members are not even, uh, biologically linked to me, although they clearly influence me as a person, let's say, no. Uh, AND as we go to upper levels, then we will find, um, um, you know, a complex situation where you can belong to a community. Let's think, for instance, uh, you belong to a football club. Life happens, uh, here in Spain, which is sometimes more important than family, uh, and, uh, as far as you belong to that particular, uh, football club or whatever club, uh, you are a member of that community and, you know, it doesn't really mean anything about genetics, but then there are some levels like, uh, some social levels, uh, in, uh, you know, in some Let's say, um, um, the small societies where clearly there is a very close relationship between, between being a member of that society and having a kind of, um, biological relationship, and then also we can, we can talk about higher levels like, uh, nation states. Most of the nation states in uh Europe and some in, in, in Americas. They were formed in the last hundreds of years. So, uh, clearly being a member of that particular nation state, it means that you will have some probably links, uh, geographical links in that, in that, uh, place, uh, and therefore this can be also explored from genetics. So, I, I, uh, and also, yeah, in the, in the higher level. Uh, BEING a member of a particular continent, um, I don't know, broad geographical areas, being European, uh, what does it mean to be European? It's, uh, nobody will, will know how to answer that, but clearly it can have a kind of a genetic expression also. Uh, AND finally, being a member of our species is also a bit unclear now because we have Um, uh, we have inherited, uh, genes from Denisovans and from Neanderthals. Uh, SO there is, uh, there is clearly a relationship that can be explored on many different levels, but this relationship is complex and needs to be understood.

10:34 Ricardo Lopes: But how much genetic variation and even genetic similarity do we find across humans? So for example, if I were to pick a random person from Europe. And a random person from Africa or from Asia or from uh South America, I, I mean, how much variation and similarity would I expect to find between them?

11:07 Carles Lalueza-Fox: Yeah, that's a very complex question also. Um, FIRST of all, variation, genetic variation is something. That is relatives and it, um, I would say that it needs to be compared. 11 good exercise is compare diversity to other species, maybe primate species themselves, um, because of course it can, well, you know, you know that the situation, it will never be like we are all clones on or that we are all different in all possible nucleotide positions of our genome that would be like, uh, you know, two extremes, and but this is never going to happen. Uh, AND then when the first, I would say the first approach is to look at diversity, uh, as, um, uh, um, you know, as compared to other, uh, close, uh, species, and then when we look at that, we discover that in, in the level of primates, we are quite uh uh not really diverse species. So we can, there are several ways of measuring this like differences in variable positions across all our genomes, and sequencing, you know, a set of individuals for each species and then obtaining, you know, statistics and comparing them. When we do that. We discover we are a, um, a very, uh, uh, species with a very low diversity and we look at the, uh, at the mammals level, then we also are in the bottom, uh, uh, low, low bottom level of uh diversity. Uh, PRIMATE species that even less diverse than us are species which are extremely endangered like, uh, mountain gorillas or something like that. So first of all, we are a a species which has a very low diversity, probably because we are a very recent species, something that uh emerged uh maybe 30 300,000 years ago in Africa, then underwent several bottlenecks, lost diversity in all the way, uh, um, and therefore, We, we are not especially variable, let's say, but then we can make other exercises like thinking, OK, um, let's look at the genomes of modern people, how many variable positions are described. For instance, I think in Europeans now with hundreds of thousands of genomes sequenced, I think we have something like 3 million positions which can have variation, blah blah. Um, BUT then when we look at this position, they are never really structured in, in, in, in a geographical, uh, level, uh, and most of the variation is spread across different human populations. So there is what we call common variants. Common variant is, is a variant, a genetic variant which is present in more than 5% of the individuals of a single species, let's say. Uh, AND when we look at all the variation, we discovered that, that many positions in our genome don't have this variation and when they have this variation, they are common variants which are present in, you know, Africans, uh, Europeans, etc. Uh, AFTER this, we can, you know, we can continue, um, exploring diversity and then what we found always in all genetic studies is that Africa has The highest genetic variation in our species, Africa, and then, you know, the people living in different African populations to the point that the rest of the world is just a sub sample of all the variation within Africa and this, uh, you know, is not an exaggeration that you can pick up two random individuals in sub-Saharan Africa and they will have They will be more diverse, more different genetically than picking up a European and an individual from Papua New Guinea, for instance. I know this sounds surprising, but really this is the situation. Uh, YEP.

15:29 Ricardo Lopes: Yeah, that's really fascinating. So when it comes to ancestry and genetic tests, because those are becoming more popular in recent years, and I really wanted to understand because, for example, let's say I've never done one of those tests, but let's say that I did and It came back with a result like I don't know that I was 2% Jew, uh, 12% Macedonian, uh, 25% Portuguese, and so on and so forth. I mean, what does that information really tell us because, um, are there really Or should we really think about genes as being part of a particular nationality or a particular ethnicity or even a particular uh religion or a particular race? Uh, I mean, does that make sense to think, uh, to think about genes in those terms?

16:31 Carles Lalueza-Fox: No, I don't think so. I mean, but, but, but, but then consider the outcome and the interpretation, the personal interpretation of these results is something that depends on each person, uh, and there are, there are some studies that apparently the people, um, is like prepared to accept some results, but they discard others that they don't like, let's say, so. So, uh, there is always a subjective interpretation depending on what you would like to be, what you would like to hear, which is very much when, when if you ask, uh, the opinion about yourself to other people, you, you just filter, you, you want to hear some things, but you discard it, the things you don't want to hear. So this is a similar situation, uh, but then what happens is that there are many of these ancestry companies. Uh, AND they are quite opaque, let's say, on how do they analyze, how do they obtain the results, how they interpret

17:38 Ricardo Lopes: in terms of their, in terms of their methodology.

17:41 Carles Lalueza-Fox: Yes, it's, uh, in fact, it's undisclosed, uh, and I am the kind of person that keeps receiving, I don't know, I would say several times a week. Uh, RESULTS from customers, you know, asking me if I can interpret for them what the companies have said, you know, because sometimes they, they told them, you know, I am, uh, 10% Viking, uh, and, uh, 5% Scythian, uh, or uh 50% uh Imperial Roman or something like that. Uh, BUT this depends a lot on the companies. Some are, let's say, trying to, you know, to, to, to give this kind of misleading information, and, and others are, let's say, more accurate, um, but at the end it depends on how do you, uh, work, how do you model the data. And also it depends a lot on how many customers do you have and where do they come from, because at the end, these companies, of course, they use their own data. So if they have, let's say imagine you, they have 2 million customers, but only a small fraction of them come from Africa, which is an incredibly diverse continent. It's very difficult. They could really uh sort out uh meaningful things about, you know, your, your fraction of African, uh, African genome. So, uh, that's a very interesting, it's a very interesting part. I would say that many, many people have this test done. I myself, I did one on, on my own ancestry many years ago, one of the most, uh, I would say powerful companies. Um, AND of course you can just laugh, you know, uh, in English, uh, person, uh, I have a section where I say that, uh, I always, uh, like this section. I have a significant percent of French, German, which is, uh, funny to put together these two countries that have been, you know, invading one another for, uh, for many centuries, um. But at this, at the same time, it's a very powerful tool for identity and some people really think uh this is uh opens new horizons in their lives and they can see themselves under a different light, but so there, therefore, it's a, it's a kind of a, an important tool. Uh, SOME people, I don't know, uh, I know some people got, uh, Jewish ancestry, significant percent, so they have converted to Judaism, they have, uh, you know, traveled to Israel or whatever, so it's not just a joke, it's something that can have a very profound impact in people who are seeking for. Uh, FOR, uh, uh, signals of, uh, of identity at the end, neither a collective or, or individual, and, and it, it, uh, and also it can be relevant for communities that have been, um, uh, let's say socially marginalized like, uh, black Americans that were, you know, the slaves, millions of slaves in North America where there are no, uh, records. Uh, WHATSOEVER. So it's very difficult. You can reconstruct your genealogical tree like we do in, uh, Europe because they were just, uh, you know, uh, destroyed or never taken into account. Um, SO at least these companies, they offer the possibility of having an idea of their ancestry. And therefore it's associated to um reparation and, you know, and, and, and social understanding of uh of of who you are. So, um I, I, I think it would be, uh, is, is, is, is a kind of a complicated subject uh for them to deal with that, with that information.

21:50 Ricardo Lopes: Mhm. Uh, I wanted to ask you, uh, also about, uh, twins, uh, uh, identical twins primarily, but also if you want, we can talk about fraternal twins, but because, um, we have, uh, studies done with, uh, twins, uh, I mean in medicine, for example, in behavioral genetics and so on. But, uh, and people, when they study twins, I mean, if they're studying identical twins, they assume that they share 100% of their genome, and if they're studying fraternal twins, they assume that they share around 50% of their genome. But is that really always the case that even identical twins necessarily share 100% of their genes?

22:44 Carles Lalueza-Fox: Yeah, so it's, it's not the case, although this is a very recent information. Nobody has, yeah, I would say, uh, you know, paid attention to that until very recently with the genomic techniques that allow you to sequence hundreds of people, let's say. Um, THE study of twins is a very classical approach to trying to sort out, um, which traits are inherited and which are associated to, um, purely environment, and, uh, it's a very clever idea if you think on that. The idea is that the identical twins are going to share 100% of the genome. Uh, AND, uh, fraternal twins, uh, twins are like, uh, brothers or brothers and sisters, but born in the same moment, uh, so they will share 50%. So any trait that you find overexpressed in identical twins as compared to fraternal ones. Then they will inform you on the, on the potential um genetic basis of any trait you can imagine, including, I don't know, perception of religion or things like that. Um, uh, THIS has been going on for uh decades, but then sometimes, you know, what is difficult to discern is the identical twin, twins also. They tend to share also an identical environment, uh, you know, the, the parents sometimes dress them, you know, with the same clothes, the same colors, and the same hairdresses, and they go to the same school, the same class, etc. Uh, SO this, uh, it, it conflates a bit the identical environment, I would say. Um, PROBABLY most of these studies, uh, still will have a problem discerning exactly the genetic basis and the environmental basis, which is maybe, maybe fifty-fifty in many, in many of the traits. But then, uh, the reason I, uh, the recent studies, the, what, what they did is just to sequence the complete genomes of all these, uh, couples or these twins. And they found they are almost never totally identical. In some cases, identical twins, they have something like 20 mutations and differences, which are difference of um arose at the very early stages of the embryonic development. I think on average it's 5.something, so it's more likely that uh to find twins, identical twins that are different in some mutations and these mutations, of course they can, can have a role in a, in a number of traits and it's very, very difficult to find identical twins which are identical genetically. Uh, SO this is also an interesting information. Now, of course, many of these genes maybe they don't have, uh, much importance, uh, but the idea, I would say is that identical twins are maybe not as identical as we, we, we thought.

25:51 Ricardo Lopes: So with that being the case, how do you think we should approach studies done on identical twins and fraternal twins as well? I mean, when it comes to the conclusions we can derive from them, I mean, how careful should we be?

26:15 Carles Lalueza-Fox: Yeah, I am not a big fan of many of these studies, uh, which are, they have problems of replication, uh, low sample sizes, difficult methodologies. Um, I would say this is kind of a A gray, um, area, you know, this is something that then especially in behavioral genetics, um, which of course is the more, the most controversial probably approach to these studies, trying to understand things such as, I don't know, um, sexual identity or things like that, uh, studying maybe 40 couples, um. Uh, AND then, uh, after some years, I discovered that there were many methodological pitfalls, etc. Um, SO it's a, it's a complex, um, it's a complex way to study, and at the end, I, I'm not sure if this is really constructive, let's say, having, you know, knowing that maybe 50%. Of your Uh trend that your tendency towards I don't know, towards, um, liking a particular food or something like that, or having a particular behavior or habit for smoking whenever. 50% is maybe due to your genes, 50% is maybe due to your environment, um. IS associated to identity again, but it's, uh, as in many aspects of my book, it's unclear, uh, if this is a really a constructive information.

27:59 Ricardo Lopes: Mhm. Right. And how about uh people who are lookalikes? I mean, because sometimes, particularly when it's, when it involves famous people, because, I mean, many people or most people know them and then uh someone appears that uh people find out that there's someone out there. Who is very, very similar in terms of their appearance, sometimes facial traits, other times even some other, uh, anatomical traits to the, to the other person. Uh, I mean, uh, does that have a genetic basis? Do lookalikes share some genes or not?

28:45 Carles Lalueza-Fox: Yeah, this, this, uh, of course, that, that it is, uh, in literature, uh, is, it has been, uh, something that has been explored for, uh, hundreds of years, I would say, you know, there are, uh, Edgar Allan Poe has this William Wilson, uh, tale where, uh, you know, this, the, the character has, you know, someone who even has the same name, and it looks very much like him. Uh, HE'S harassing him, uh, for, for years while he's trying to destroy himself and say, uh, the Fyodor Do Dovstoyevsky also has, um, uh, tail, uh, which is the the double, uh, and it's never clear if the, the rest of the people, they see the, you know, the similarities, and, you know, it's unclear if it's just a particular obsession. Um, SO the, the idea of doppelgangers, this idea of a double that, you know, exists, a double of you, usually is a double that has a different moral meaning, you know, usually, uh, it's a bad omen, but sometimes in like in the case of William Wilson, the double is, uh, is virtuous, and it's you, the narrator who is, you know, the, um, going into the, into the, into a downfall. Um, BUT now in the 21st century with the social media, this has exploded. I mean, it's uh lots of, it's kind of, kind of funny. I mean, some of them are really, uh, striking people who finds in the internet uh double of himself or herself. Um, AND you can even play that in the past, uh, and I, I remember I, I was, uh, I saw some images of, uh, I think, I don't know, uh, uh, Nicolas Cage, uh, during the, the, the North American Civil War, someone who looks exactly like him, but, you know, dressed as a Confederate soldier, um, and of course. As usually in, in science, but you know, um, uh, legitimate question is, well, why do the people, the people can look alike. Do the, does it mean they are family related? Does it mean they came from the same geographical area? Does it mean they, they have, they share some genes, I would say genes associated to facial morphology, of course. Uh, AND I was involved, involved in, in the first study on lookalikes, uh, a couple of years ago, uh, where we, we took advantage of one of these photographers that was making couples around the world, and we asked some of these couples if they wanted to, um, you know, to get analyze their genomes and compare and see what happened. And we uh with, um, um, with some of these couples, uh, and then we, we explore several levels of, um, um, similarities. The first one obvious is, uh, are they family related? Maybe they are, you know, second cousins or third cousins. I, they don't know. This was not the case. They never, they were never family related. Uh, YOU can, you can, you can look at the internet. Some of these, they, they really look alike. I, I, some of, some people have beards and maybe they look more similar, but some people are really very, very similar, strikingly similar. Uh, um, WHEN we look at the ancestry, they tend to come from similar geographical region, which it makes sense. Uh, I remember one case, however, where one of the individuals was from Germany and the other one from southern Italy. They look exactly the same, um, and then, uh, of course what we did is look at the rest of the genome, one discarded they were not, you know, they were not really, not family related. Uh, AND then we found they were, they were sharing kind of hundreds of variants which are described associated to facial morphology which makes sense and interestingly, uh, most of them were sharing also. Uh, MUTATIONS in genes that have been described associated to kind of dietary habits or, you know, smoking behavior or things like that beyond just the morphology. So that's a very interesting idea. I think that you are. Similar to someone else, not just because the structure of your face, which, you know, it depends on a lot of genes, but at the end it's a finite number of genes, and we have like, uh, you know, 8 billion people in the world. So clearly all of us, they, they are, we are going to have a double somewhere. Uh, BUT also because some of the genes are probably associated to dietary habits that also shape our personality and our, um, you know, our, our look at the end.

34:00 Ricardo Lopes: Mhm. So, I, I would like to ask you about a topic that, uh, very unfortunately nowadays is extremely politicized, uh, I mean, for several different reasons, but, uh, when it comes to sex, the Determination, I mean, in what ways do the sexes differ genetically and how is sex determined when it comes to development, intrauterine development?

34:31 Carles Lalueza-Fox: Yes, I mean, uh, the sex determination, as, uh, you know, operates at different levels, and, uh, in any of these debates, what is important is not conflating these different levels because then it becomes a mess, and I think it's what's happening. I would say almost any biologist would agree there are two biological sexes, uh, one that, uh, you know, based on the gamuts they produce, one produces mobile, small gamets. The sperm and the other one produce uh big um um immobile gametes which are the, the eggs, uh, and of course this production, this structure, it has um a genetic base, a genetic structure. But also this, uh, once you have this genetic structure, this has to go to upper levels to end up in the physiological level, and these upper levels, um, involve uh hormone productions and hormones involves interaction between, uh, hormones, uh, physiological development. And at the end, at the very top level, then there is, you know, maybe a psychological also association and, or the social perception of uh these, uh, two different biological sexes. As, you know, you go to the upper levels and the social levels, of course, uh, where we can talk about gender, uh, then it's when it becomes more, uh, messy, let's say. But also at the basic chromosomal levels, many things can happen, of course, uh, because, um, for the um development of these uh biological sex, you have uh genes that that generate a specific hormone that then develops, uh, you know, into testes and the other one into ovarians, and then maybe there is a deletion of that particular gene, so you can, I don't know. You can be, for instance, um, um, XXX, so instead of being, uh, you know, um, like a biological female, you have a, you know, maybe the gene that is in the Y chromosome and you have inserted in the X chromosome, so you can have Uh, like, uh, male, uh, traits, uh, being chromosomically, uh, female, etc. There are many of, many of these, uh, complications, let's say, but it doesn't mean that there are many, many different sexes, and it means there are two biological sexes still. VERY much the same way that we, you know, we have a Down syndrome and people have uh 3 copies of the 21 chromosome, but the, the general plan of our species is 23, uh, you know, couples, so 46 chromosomes. Uh, SO that's, that really does not invalidate the general rule, but of course, it complicates things, as I say, especially. When you go to gender, gender, I would say is the social manifestation of these biological sexes where people, um, they, people, they don't, some people don't think, feel comfortable, uh, with the social rules, uh, where you, you are, uh, let's say, placed because of your biological sex, which is absolutely legitimate. But in these debates, they usually what what happens is that people conflate the biological reality with the social reality, which is of course uh um uh creates confusion.

38:19 Ricardo Lopes: Yes, and it's very important, I guess here to mention that or to emphasize that the genetics of sexual, uh, of sex determination and sexual development does not invalidate the reality of gender, right, because some people pick up on the. Genetics or the biology, the, the phenotypic traits in terms of primary sexual characteristics, for example, to say that, uh, I mean, there's only uh sex and it's only sex that matters, but that's not really the case, right?

39:02 Carles Lalueza-Fox: No, really, I understand perfectly. Some people can feel. Uh, YOU know, this basic representation of being just, um, biological male or bio biological female, not, not to mention these intersex, uh, let's say, um, specific cases, uh, does not really in terms of identity represents themselves. Um, SO, uh, uh, I, I, I, um, but, but not only in this case, I would say that in the case of Um, uh, census and race attribution, for instance, something that happens in the states where you have to define yourself, where which race do you belong or which ethnic group do you belong. I, I perfectly understand that some people feel uncomfortable being defined in such a narrow sense, and this happens in, uh, absolutely the same. In the same way, way, I'm only saying that conflating all these terms at the end, it creates uh confusion, uh but also invalidates at the end the use of uh scientific parameters, so it is like render them, uh, absolutely, um, and you know, uh, uh, in an, in, uh, useless for any scientific, uh, approach which I think is unfair also. Otherwise we cannot understand evolution in, in our, uh, in life if we don't understand there are two basic biological sexes.

40:33 Ricardo Lopes: Right. Um, WHEN, uh, in the book you also talk about the genetics of, uh, kinship. Uh, I mean, from the, from a genetics perspective, uh, what is, uh, family

40:47 Carles Lalueza-Fox: exactly? Yes, well, as I mentioned, a family is, let's say is, uh, you, you can consider a family, the, your, um, genealogical relatives. Um, ALTHOUGH I, you know, I mentioned at the beginning, not all your family members are genetically related, but let's, let's focus on the, on the basic genealogy where you have 2 parents, 4 grandparents, 8 great-grandparents. Etc. So this is something that so far it has been explored from genealogy looking at uh records, let's say at at a certain level it it becomes very difficult because the information is missing, etc. So after several generations, you, you could, you know, double the number of your ancestors, but it's very difficult to get the information and in some cases in Europe, you maybe can go like 500, 600 years ago. Uh, SOMETIMES in the royal families, you can even go, you know, close to 1000 years ago. Um, THE, this is genealogy and this is something many people consider. VERY important for their identity perception because you are root in a particular family, you know your ancestors, you research about them, you know, you became identified with them when they were heroes in the First World War or they were traitors and who were killed. Somewhere. So there is, there is this, uh, this, um, different perception and it has been studied. Some people distressed to, uh, to discover, you know, some of their ancestors. Some people feel proud, etc. Uh, WHAT happens now is that we are in, in, in a, in a situation where, first of all, we can Explore genetically these ancestors well beyond any genealogical record and very soon we'll have ancestors which will be real genetic ancestors that will be placed in the Middle Ages, of course, beyond any possible, uh, any possible information from any church or whatever. Um, AND the other thing is that we will be able to build up pedigrees up to millions and millions of people. In fact, some of them have been already built. Uh, I don't remember. I think it's, there is some study with 4 million people, etc. Uh, SO we will be connected at the, at, at a, at a level that we would never have dreamed about, uh, some years ago, a few years ago, thanks to just computational developments and thanks to the power of new genetic techniques. So the idea of family and the idea of genealogy will expand to a next level where you will be able to find connections with people in other continents, uh, hundreds of years ago. Uh, ETC. AND this, of course, you know, if the genealogy already creates a sense of belonging or a sense of genealogy, a sense of identity, just imagine when you will have all this information. Maybe you and me are connected and for sure we are connected, but we will discover we are connected. I don't know, in a specific individual, uh, 20 generations ago in, uh, I don't know, in Portugal or whenever, uh, this information. Uh, THIS is not, not, uh, science fiction. This will be available more and more in the next years and it will be, uh, really, it will have, of course, um, uh, uh, results in, in the, in the perception of, uh, belonging and, and in the collective perception also of identity.

44:44 Ricardo Lopes: But when it comes to how we understand our genetic ancestors, I mean, what is, for example, the probability that we inherit any genomic fraction from a specific genealogical ancestor after just a few generations? I mean, should I Expect for example to have a genetic fraction of my great great great grandfather or for example, yes,

45:16 Carles Lalueza-Fox: yeah, I mean, uh, yeah, I mentioned we have 4 grandparents um and, and then we would expect 25% of our genome coming from each of them, but, but. But the chromosome, they break at different places, they don't break and, and, and the chromosomes are different. Some are very, very large, some are small. Uh, WHAT happens already is in the, in the level of, of our grandparents. Uh, WE don't inherit exactly one quarter of, uh, of our genome from each of, of, of them. So what happens already is, uh, instead of that, sometimes we inherited from one of them 30% of our genome and from the other one instead of 25%, just 20%, let's say it begins to fluctuating. And this goes on and on and on each generation. So if we go, for instance, 6 generations back, if I make the numbers correctly, uh, uh, we should have 128 ancestors, genealogical ancestors, but because of this fluctuation, Already we have some, some of these 128 that didn't give any single fragment of their genome to us. Of course it means that some others of the 128 will give us the double or triple or whatever of their genome to us. Um, SO we have to distinguish between our genealogical ancestors, which are these, that go doubling every generation. By the way, in just 50 generations, it became like more people than atoms in the universe or something like that. So it makes you wonder, of course, because we are all interconnected and repeated, etc. Many ancestors are just repeated in our genealogy, uh, but these are our genealogical ancestors. If we look at, at our genetic ancestors, they're just a tiny fraction of the genealogical ones. So again, it becomes what is more important to, to have one specific ancestor. Like imagine you have a king or a queen. Uh, IN the Middle Ages, it was your ancestor. Uh, AND you are very proud of that. But then when you analyze the genome of this king or this queen and your genome, you discover you have not a single fragment because of this uh fluctuation. So, uh, you know, what is more important, to be a genealogical ancestor or to be a genetic ancestor. By the way, uh, these genealogical ancestors, which are not your genetic ancestors, they have influenced some of your genetic ancestors, of course, either. You know, giving them a specific fragment of their genome that subsequently get lost and, and didn't reach you or by influencing them, you know, as a person, um, shaping their personality and, and their education, etc. So here's a very interesting discussion. What is more important, shaping your descendants, let's say, through your intellectual contributions or just giving a specific fragment of your genome and sending it to the future, like maybe this is more important, but it is up to you to decide, I think.

48:43 Ricardo Lopes: Mhm. So, uh, let's say that we are studying history and we study the genetics of, uh, royal families of elites. Uh, CAN we extrapolate from them to the genetics of their subjects, uh, to any extent?

49:05 Carles Lalueza-Fox: Uh, NO, I don't, but yeah, that's a very interesting question. Also, some years ago I was involved in the, in the genetic study of some released, uh, from the French royal family that were, you know, executed during the French Revolution. The remains were, um, destroyed, um, then retrieved, uh, during the restoration. Nobody knows for sure. But some things like blood, hairs, uh, etc. ARE floating around claiming to be from Louis 16 or from Marie Antoinette, etc. Um, SO I was involved in, in, in, in some of these studies, uh, and one of the things, uh, I did is to model the supposed ancestry of Louis X6. Just looking at their ancestors, uh, which are known, and I went back several generations, uh, and, and it was funny because at the level of, uh, the grandparents, I think, um, of the 81, grandparents, I think he only had one French. Of course he has to have a French because if not he wouldn't, he wouldn't be the king of France, but the rest were from Austria, Poland, uh, North Italy, the other. Places because the, you know, the complex political situation of Europe at that time where a powerful country was very difficult to get married with a princess from Spain or from, uh, Great Britain because it will, uh, you know, create a conflict for sure. Um, AND, and, and so that was interesting, uh, the King Louis XV. Uh, uh, GENETICALLY was not a representative of the French population. The French population had been, you know, you know, being French for several hundreds of years because of the difficulty of the people moving in that, uh, in that time in any country. Essentially you were marrying the neighbors for the last hundreds of years. And another interesting thing in, in, in another royal family like the Absburg in Spain, they just married within the family, so they created a kind of an endogamic monster that ended up with Charles the 2nd, the bewitched. Uh, WHO was, uh, accumulating so many, uh, consaninus, um, you know, ancestors, uh, really crazy. I think 0.5% of, uh, his genome was in homozygosis with no variation at all, something unbelievable, uh, and he had, of course, many ailments and many problems and died without, uh, without children. So in these two cases, which I think are very representative, one is the trend towards endogamy that happens in royal families where you cannot marry anyone below your level, so you have to marry within your family, it's kind of crazy, uh, or for political reasons, you marry someone else, um, but you really don't represent genetically you, the country, uh, you are ruling upon. Um, SO if we could analyze the genomes of all the royal families in Europe, for instance, in the last hundreds of years, we'll probably discover they are very similar. Uh, THEY form a specific population which were very similar to one each other, like a small cluster, like if it was a different population from the rest of the, of Europe.

52:48 Ricardo Lopes: So, I mean, uh, it's interesting uh because of course, as we've already mentioned, when, for example, earlier we talked about sex determination, some of these questions get very politicized and many times they are very unfortunately uh misrepresented or the science behind them are is misrepresented by uh politicians and uh the pop uh the general population, but, uh, I mean, are there, for, for example, because Particularly now, uh, people, uh, uh, um, there, there are some narratives going around in regards to immigration and people from, uh, for example, outside of Europe, immigrating here. Um, I mean, does the idea of a pure populations make any sense at all, and does it make sense for people to worry from a I mean, if we're talking about the science here, of course to worry that their race, their identity might get, uh, I mean, tarnished or might get contaminated by breeding with people from other, from other places, people from Africa, from the Middle East, and so on.

54:17 Carles Lalueza-Fox: Yeah, I mean there are, there is this political narrative all around I would say in those times. Uh, IT doesn't make sense to me, uh, the idea of races, I think it's scientifically not supported. In fact, one of the things we have learned in the last 15 years of ancient DNA studies is there are several layers of ancestry which are over. Imposed, uh, and there are these, this, this ancestry, these ancestry layers that maybe are slightly different from one population to to another, but it's very difficult to argue that there is any single population with a single ancestry when there are all these layers everywhere, um, so this, this is one question, but of course when we think on distant uh immigrants or whatever. There is also the temptation of, uh, of a kind of uh Making genetics, uh, into politics, um, and I would say this is unavoidable, but at the same time, uh, there is a lot of, you know, genetic information that needs to be explained, uh, correctly. The one thing is that you can explain it correctly and then the politicians can also ignore it, uh, but, uh, at least we have to make the effort to, um, to explain things correctly. Um, BECAUSE among other things, one of the messages also we have uncovered from all these years of paleogenomic, uh, investigation in, in humans is that, is that migrations have been prevalent. In the last thousands of years with lots of layers, replacements and and situations, of course, some of them associated to nasty things like social inequality, but the social inequality is also prevalent today in our societies. So I think there are many things to be learned from the past. That could help us to understand a bit the present also, but the temptation of misunderstanding is always present, not only in, in sound genetic studies, but also in what I mentioned of these ancestry companies. These ancestry companies, they can have a A huge social impact. So it's not something that you can say, well, you know, it's a private business and it's, you know, nothing happens if they misrepresent their results, the, you know, the, the social consequences are for us anyway. So yeah, we are, we, we. We are in an interesting times where all this information, which is very powerful and can be very positive in many ways if properly explained, uh, they can also have negative consequences.

57:12 Ricardo Lopes: Yeah, yeah, but I think it's uh either way it's important for scientists particularly, I mean, for the experts themselves to clarify that, uh, I mean, even if people don't listen to them because of the particular political economic context they're living in and so on, uh, I mean, it's important to clarify that uh ideas that are promoted, for example, by the far right, the conservative right, related. That, uh, promote racist ideas, xenophobic ideas, uh, ideas related to, um, I, I mean, as I was saying, race and or a pure identity or a pure population, whatever that might mean, and then also sometimes they might promote forms of eugenics that uh none of that is supported by science,

58:11 Carles Lalueza-Fox: correct. Yeah, yeah, sure, I mean, uh, science, you know, it has the obligation of explaining themselves the result, uh, the, to the, to the public, the results, but, uh, the public, you know, the society has the obligation of trying to understand the genetic results and, you know, and therefore well things like that we are trying to do. To do here is uh is a bit like that. It's not just a responsibility of the scientists at the end, but also the the society of being more informed on how these results can be interpreted and they need to be digested. So, uh, there is a, you know, a mixed responsibility on this, otherwise it will never be completely fair, let's say.

58:58 Ricardo Lopes: Mhm. Uh, BUT uh, I mean, what are perhaps the positive ways or the positive messages that we can get from, uh, human population genetics and from studying, uh, genetic diversity, genetic variation, but also, of course, genetic similarity. I mean, what are some of the positive things or positive messages that we can, uh, derive from that?

59:28 Carles Lalueza-Fox: Yeah, there, there are many positive, uh, messages. The, the first one I mentioned already is the, the fact that there are no isolated or pure populations in any sense you can imagine from a genetic point of view. Uh, SO there are no mutations that are present in all individuals on any population you might, you might describe from a social, cultural, or even geographical point of view. Uh, WHAT, what we have is that these shared ancestry levels, layers, uh, in slightly different proportions depending on the situation in the world or in the continent or whenever, but this means there is no point in talking about populations are isolated items. Uh, BUT also this sense of interconnectivity of belonging. Uh, I mentioned, if we go back several tens of generations, we'll have more ancestors than people have ever lived in the world. How, you know, could this be? Uh, IT'S just because we are all very tightly interconnected. We share hundreds and hundreds of ancestors, any of us, including people from a very distant place, uh, you know, in Australia. Um, AND another thing is that very soon we'll be able to find these ancestors, uh, you know, scattered all around. We'll be able to distinguish these fragments of chromosomes which are identical because descendants. Um, YOU have to imagine that you are, you know, I don't know, 1000 years ago, your genome is scattered in many different sites, archaeological sites where people are buried there, and these are real ancestors, um, well beyond any genealogical record you can even dream of. Uh, YOUR genome will be scattered in 1 million fragments, but all, any of these individuals, some of them are going to be found. Uh, THEY will be your genetic ancestors, your real genetic ancestors. Some of them bringing you a small fragment of the chromosomes, you know, 20. At the same time, you can think on the future in the same way. Uh, EVEN if you don't have kids yourself, someone, a cousin, uh, you know, a grandfather, your brother, whenever we have kids, and Your genome in the future, 1000 years in the, in the future will be scattered all across the globe. Uh, SO this interconnection is a fantastic image. It's difficult to visualize, but it, it creates, it's real. It's not just a metaphor. Its real because it could be investigated. It could be sequenced. Your genome could be sequenced in the future and find these millions of fragments scattered all across the planet in many different populations and many different people. So I think it's a very. Uh, IT'S a very positive message if we, if you think on that. Not only that, if you go back to the Neanderthals, for instance, we already know we have about 2% or 2.5% of their genes in our genomes, you know, especially outside Africa, in, in, in populations like Eurasia, Asia, and the Americas, uh, and these people, they are extinct, but in many ways, His, uh, genes are still around us, connecting ourselves with people who separated from our lineage more than, you know, half a million years ago. I think it is a fantastic image, uh, for, uh, considering ourselves as members of a single large and extended family.

1:03:19 Ricardo Lopes: No, yeah, that, that image of interconnectedness is really very uh positive and, uh, uh, I mean it, and, and it has a sci a proper scientific basis, so it's, it's very important to, for people to know that. So, uh, I have one last question then. uh, I mean, as new The technological developments in genetics occur as, I, I mean, as we develop new techniques, acquire more knowledge. Do you think that in the future, there could be new concepts, new categories of genetic identity?

1:04:01 Carles Lalueza-Fox: Yeah, I think so. I think, Jeanette, uh, you know, identity is becoming an important concept in, in the 21st century. At some point we thought we are going to the globalization and history will be lost and we will be all happy. Uh, AND in the last 5 years we have been a have seen a contraction of this globalization. We are now emerging in the Second Cold War, maybe in regional areas like, uh, you know, America, North America, maybe Europe, maybe China, etc. Uh, IN this context of conflict between all these regions, I think identity is emerging again. Um, IF, if, if it has disappeared, I'm not sure if it disappeared in the last decades of the 20th century, but it is emerging clearly as a signal, uh, of perception and, and belonging, uh, and therefore genetics is emerging as a tool for identity, as I mentioned before, well beyond any other tools that we can imagine like genealogy, for instance. And therefore this tool needs to be used in a proper way. It needs to be used as a positive tool. It can be used all the other way, you know, as a very conflicting and negative tool, but at the same time it has the possibility of being used for good. Uh, AND I think, uh, we'll see many new developments of identity, many interconnections of identity with genetics, which is a very powerful scientific tool, uh, and therefore I just, I wanted to explain in my book, uh, these, all these possibilities always in the positive sense because, uh, you know, the negativity will, will come out eventually from other places.

1:05:54 Ricardo Lopes: Right. OK, so the book is again Identity, what DNA can tell us about Ourselves, and I will be leaving a link to it in the description of the interview. Uh, Doctor Loweza Fox, just before we go, uh, apart from the book, uh, are there any places on the internet where people can find you or your work?

1:06:18 Carles Lalueza-Fox: Um, NO, I think I express myself better in, uh, in books than in public speaking. No, no, I don't know. Uh, AT least in books, you can really, um, explain yourself and, you know, in a thoughtful way, uh, in a moment where, you know, we see the president of the world speaking immediately. Constantly in, in social media without thinking. So at least let's, let's hope we can think a bit about, uh, you know, about these complex subjects and, uh, you know, writing and thinking is the best way of, uh, of going through.

1:07:00 Ricardo Lopes: Yeah, I, I, I agree. So thank you so much for taking the time to come on the show. It's been a real pleasure to talk with you again.

1:07:09 Carles Lalueza-Fox: No, thanks to you. Goodbye, Ricardo.

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