Evolutionary diversity arises primarily from changes in gene regulation rather than the invention of new genes, meaning that the same genetic toolkit is used in different ways across species to create the vast diversity of life forms we observe in nature.
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Загадките на еволюцията – интервю с проф. Шон Б. КаролAdded:
First of all, many thanks that you agreed to share some thoughts with with us and with the Bulgarian public u because uh it's you know um you personally for me you are one of the people that uh um let's put it that way that inspired me in the field of developmental biology.
>> Oh well that's very kind of you. That's gonna that's going to make an Irishman you know blush. My color is going to change now. So yeah.
>> Yeah. But but uh but the the real the real reason I I just want to start with this one. The real reason that we are together is that finally uh we have ink hard cover in hard coverver your book from yes uh endless forms most beautiful uh translated not by by me but I am a scientific uh scientific reductor of it editor. So if if there is any mistake you know who who to blame.
>> I'm not going to catch them as you know.
>> Yes.
>> Okay.
Uh so um my first question um because you know uh as a kid I used to read Conan doll and he has a nice book nice book um not about Sherlock Holmes uh but about scientists and uh you know of course the book and there is a certain character there professor challenger who is very much against um the the very idea a that scientists should waste their time for um popularizing science. So there is a a famous place in which he actually he said okay don't make this mistake.
Professor Wley with all my respect he's just like a parasite he well he he use the the efforts and the the you know everything that the researchers do in order to to gain some popularity but I myself am a a popularizer of science of course not in in that scale so what's your opinion on that Should we waste our time on Yes. on making on making u um popular interviews, books, films? By the way, I I just saw that you have a film from 2022 that I didn't watch by the way.
>> Well, um no, I Yeah, I I I see the role of science in our in our culture and and global culture, right? And science, if I may say, I think science comes closest to maybe the ideals of the United Nations of almost any human endeavor.
Here we are speaking, right? We're from totally different backgrounds. We know that there's, uh, norms of how scientists engage with each other around the world, about how we collaborate, about how we share information, things like this. And so uh I think the scientific world has a lot to offer society in general both understanding you know how scientists think uh how scientists work together um it's actually a pretty happy story you know most of the time right and then what we find out and I I think in terms of our culture you know the the whole adventure of exploring nature and of revealing uh you some of how nature works. That's that's things that society can enjoy, I think, and and can can get some meaning um out of. So, I think science has a lot to contribute to culture much as art or music or literature does. And it can only make that contribution to culture if you actively make the effort to bring those insights, bring those discoveries, you know, into the culture, which is generally going to be through media, right? it's going to be through books and podcasts and >> movies and and things like this and and and there's maybe there's that that I would think is maybe the more idealistic view of what science can do for culture.
But there's I think a very practical view which is in most countries the public support science. So to have that public support the public should in return understand what scientists are doing, why they're doing it, what they're finding out. um how that might impact their lives. And scientists have to be part of that conversation. It can't be left to just third parties. We we have unique insights because we're we're the adventurers, right? We're the ones that journey into the unknown and and and see things that haven't been seen before and think things that haven't been thought before. So, of course, we should be involved in communicating that.
>> Okay. Great, great answer. Usually, uh I uh when uh when somebody has to rationalize uh because that's quite a quite an effort. You you should you know spare some time to uh think how how you can uh for instance how how how you deliver to the public the concept for Hawk's jeans.
I even had I even but I I'm not wearing it now but I have a t-shirt >> with a drosophila and a question that pops up out of her head and an inscription which says what the hawks.
>> Yeah.
So uh but um but usually people sent the the process of rationalization like okay um we as a scientists should should be involved in public communication in order to convince people to give money but that's only one of the reasons and you put it very well. So uh our role is also to bring to the attention of the general public that science is equal as equal part of the equation uh to the contribution of the humanity uh as as well as the the arts and also lit literature and something like okay so back to your book. So in in endless forms most beautiful and once again what a title it's like you know uh of course >> I stole it from Darwin. I mean you know there goes to Darwin but but Steinbeck did the same. Steinbeck did the same. So um Hemingway did the same but with the Bible. So you you literally he had a great example. So you emphasized the role of gene regulation over gene invention.
Um >> yeah how how did this shift change our understanding of evolution compared to earlier gene centering views? Yeah, I think uh you know I I was lucky enough to be part of you know sort of a revolutionary change in thinking but that revolutionary change in thinking came because we actually were able to get answers to some questions and when I was a when I was a graduate student or maybe just as I was beginning to be a graduate student um none of these genes involved in bodybuilding and body patterning had been isolated and I was just hearing rumors you know and you had to go around and talk to some people.
But the expectation at that time and because I was working I was getting my PhD in immunology and and that was generally studying you know mammals, furry animals.
The expectation was that the making of a mouse or a human and the making of a fruitly would have nothing in common. Right? These were entirely different branches of the animal kingdom and you know we have bones and flies don't and you know and we have big brains and they don't etc. So when the first uh genes were isolated that were involved in so-called hawk genes and then they were found quickly found to have counterparts across the entire animal kingdom including you know you and I and to be arranged in clusters like we saw them in fruit flies.
This really uh was shocking. It was exciting. It was thrilling, but it was shocking and it made it it caused a complete rethink. And I would say no one I know or no one I know of has claimed to have predicted that result that no biologist saw it coming that a similar set of genes would govern the building of animals as different as worms and flies and humans and elephants.
And then that forces you to think, well, what does that mean then? If we find that there's there's some genes in common in bodybuilding, what does that tell you? And it I mean, the first inference you'd make is a lot of the animal kingdom has been constructed using a similar we say sort of toolkit of genes. So you're kind of inching, you know, you're kind of making this sort of really big conceptual turn from thinking that they had nothing in common to now realizing they have something in common.
But nonetheless, you know, we are different animals from fruit flies, you know, and butterflies are different from fruit flies and lobsters are different than shrimp and all that. So you still say, well, what makes them different if you have similar sets of genes? And then that that's really one of the you know so I think maybe the prime you know one of the principal discoveries of evodo was that these genes are shared but the second thought then is okay well then how do you make different types of animals and you make different types of animals by using these genes in different ways and much is the way you use tools in different ways and you make different you know uh constructs in your in your you know carpentry shop. So that's that's that's how I don't know if I'm quite on the nose to your question, but the the big change of thinking was prompted by shocking discoveries that led us to say, well, if the genes are going to be so similar, then how do you get diversity? And you get diversity by using them in different ways, expressing them in different ways.
>> Yeah.
about that because um you know of course you have cited this great thought of Dubranski that and I I also do in my lectures I emphasize on that that nothing in biology makes sense except in the light of evolution.
Um, speaking of evolution, um, many people still still think that evolution works mainly through mutations in protein coding genes.
>> Yeah.
>> So, uh, why is gene regulation such a critical piece of the puzzle? Because I I'll put aside this part of people. So this group of people that think that evolution is something in which you can believe or not we are not going to speak about them.
>> No.
>> Yeah. Well, so yes, why the importance of of of regulation? Well, what this part of this is the historical explanation of this is that for the longest time in in reading DNA, the parts of the DNA we could read were that that were decoded into proteins. We we disco we deciphered the genetic code in the 1960s.
When biologists grind up cells and tissues or they analyze blood, they're usually looking at proteins and so they look at what you know how proteins are encoded in the DNA. So we had a very protein centric picture of life but we hadn't addressed sort of the choreography of all this. And so let me sort of start back and I think and maybe you know listeners or readers don't start with this bias but but imagine this that you're going to go from a single fertilized egg a single cell to depending upon the creature up to trillions of cells right that are differentiated into hundreds of different types and organized into tissues and organs etc. Where does that choreography come from? And it's a it's a it's a ballet of time and space.
Events have to happen in a certain order and they happen in a certain relative space one to each other. And and so that information is in the genome. It's it's in the DNA, right? But it has to unfold.
And that's what regulation is.
Regulation is determining where in time and space genes are active or inactive.
And that's the choreography that one needs to build a a a complex creature.
So the way I try to boil it down the relationship is is to think about development. Everyone it's a development is of course one of the most spectacular things that happens on our planet. A single cell becoming a complex creature and anyone who's a parent you know can really appreciate this uh you know if you've been through that experience it is just sort of amazing and it's there's no end to that. By the way, by the way, I have I have in my thermostat now few chicken embryos, but I'm not going to show them because we it will be broadcasted this interview and I am performing an exov experiment.
>> Okay, that's great. That's great >> you know with my students. uh in order to to evaluate the oxidative stress and etc etc but but still the because you know since the time of Aristotle uh people have told who how can in 21 days you you can observe every day every day the development of a chicken and >> but what was the difference because Aristotle just had the power to observe and so he said okay I'm going to crack this egg every day so I'm going to crack it on day first day second day >> and he came up with this idea of preformation >> but now we have the tools now we have a modern labs and now our um our understanding of these processes is uh very very evolved from from this time >> exactly and and what the developmental biologists of the 1980s and I was one of them, you know, they enjoy it. But we were making the kind of images that that's part of your backdrop, which is we were able to go in and look at embryos moment by moment >> and see the chemical changes that were taking place in embryos before the physical changes >> that we would see with the eye or see in a microscope that was the making of a particular tissue or the making of a particular appendage or whatever it might be. So we understood there was all of this genetic activity going on that foreshadowed the making of you know body parts and tissues and things like this.
So there there would be no evolution of development. There would be no evo without the D.VO. The D.VO was a huge revolution in biology and now understanding how complex creatures are constructed.
But once you understand that that there's this choreography, >> it's a small I well hopefully it's it's not too large a step to understand that differences in physical differences in creatures come about through changes in that process.
>> A little a little tinkering over here, a little change over there, you make something a little larger, something a little smaller, you start building something a little sooner, you put it in a different place. All these things are changes that happen during development that give us the diversity of creatures that we see out in the world. So the so development and evolution are closely intertwined because development is the making of an individual and the evolution is the is the emergence of all these different kinds of things by modifying that developmental program.
And so, um, all this is is is about regulation because there's so much in common to what animals have genetically, but how they use them in building things in in time and space, that's that's where the real differences lie.
>> And and that brings me to the next question. So, um, Evo Divo, a very complex field which bridges together genetics, embryology, evolution.
uh what were the biggest challenges in integrating these fields uh into a cohesive discipline because now I'm working in the field of astrobiology that's my let's say last effort I I'm the director of our uh master program of astrobiology uh and uh astrobi you know it's a huge field with a lot of interconnecting disciplines and I face a lot of let's say tension in order to uh to put the efforts of our team in in one direction or or at least three directions.
>> Yeah. Yeah. Well, I I think as you mentioned, Evodo does bring together different disciplines. So certainly developmental biology or embryology as we call it, genetics because you know genes are the things that change and do the work right through through time and space and evolutionary biology at large.
Like some of the most enthusiastic people for evo were paleontologists >> because paleontologists can see this deep history of life, right? And say, you know, we know, you know, birds evolve from dinosaurs, we know the history of mammals, etc., etc. And what the new evo gave us were ways to actually ask about the origins of structures, the origins of these creatures. So, you know, how did a fish fin become a walking limb? Right? So we know from the paleontology that happened but now we can understand from evodo by comparing what happens in different creatures creatures that make fins creatures that make limbs what's the same and what's different. So that integration meant that meant paleontology was integrated that meant that what you would sort of call population genetics which is more about variation that exists in populations. So evolution is you know, enormous in its scale because it considers things going on moment by moment in the world, but also considers, you know, the 3.8 billion year history of life. And so, Evodo steps in and says, well, how how have differences come about between creatures? How do you get a new structure? How do you paint a spot on a butterfly? Right? How do you change limb number in a cat in a caterpillar or or in a shrimp? And you know, evolution prior to this sort of breakthrough of of evo, we couldn't answer that question because we had no idea how animal forms or plant forms were made, right? We we we were we were just spectators to this incredible pageant watching development, but we didn't know what was going on in the inside. So, of course, we didn't know what precise changes happened to give us different kinds of creatures or to give us different structures. So, very integrative. Um, and I think that I kind of circle back on this. You know, this has a huge aesthetic element. You know, people love nature. If you love flowers, well, the evolution of flowers is interesting. If you love animals, well, the evolution of animals is interesting. And I think Evodo allows you to tap into that sort of love of nature, that love of diversity, because you're you're seeking an explanation for how that diversity came about. And um and there was a very strong aesthetic dimension to this work because watching embryos develop it's beautiful right and the like the images you have behind you I mean that's it's a beautiful image and I think that drew a lot of talent into the world in other words in the early 1980s it wasn't clear that Evoda what didn't even have that name it wasn't clear that this line of research was going to explode but once it started to find out really exciting things and seemed that more and more questions were accessible it drew a lot of talented people from very different fields um who are like I I want to understand you know the say the making and diversity of the animal kingdom. Well that's going to integrate viewpoints and expertise from lots of different areas.
Yeah because you mentioned paleontology.
So um why certain forms never arise despite seeming possible? I I I I wonder because you know um a lot of science fiction a lot of non-scientific fiction. So uh like why we don't see animals with wheels or birds Yeah. birds using some quadricopters instead of wings.
>> Yeah.
>> So and why why for instance we don't have six leg mammals.
>> Yeah. Also, we have hexapods, but why don't we have six leg mamas? That that's one of the questions that buggles the minds of young zoologologist. Let's put it that way.
>> Well, we can have a lot more fun that those questions were around 40 or 50 years ago, but we can have a lot more fun with them now because, you know, we understand more about the program that, you know, makes these structures and you can start to say, okay, well, why don't you have a six-legged animal? Um, well, let me see. Could you could you modify things in such a way you sort of think it just may be too hard to get from four to six? You know, it it's probably not that hard to get from six to four or to get from 8 to four or even to get from 12 to four. But to get from four to six, given all the other stuff that you're trying to make, maybe that's you just can't go there. But then you look at things and you say among the mammals, you know, look at the look at the evolution of aquatic mammals, right, from terrestrial ancestors. I mean, that's pretty amazing, right? Um, so you know, four-legged animals evolve from fish. So fish came, you know, fish came to land to give rise to four-legged animals. And four-legged animals have gone back to the water in the form of of um, you know, aquatic mammals. Well, that's not your six-legged animal, but that's still pretty stunning, remarkable stuff. So, I guess you can you can choose you can have fun studying what has happened, and you can have fun imagining what didn't happen and why.
Yeah. No. No. Because the apparently you can use for instance chicken embryos.
Yeah.
>> You can simply put a beat of FGF8 >> and you will uh you will receive another epical reach zone in the middle between between the the limp and and the the wing. So you can you can make a lot of crazy stuff but that didn't happen in nature. So >> yeah.
>> So for some reasons. Yeah. So much.
Yeah. They they may not compete that well with the other four-legged creatures or other winged creatures out there. But >> yeah, and and I think it gives us some sense that >> there's a lot of potential there. Um you know what what what avenues get explored, you know, is determined by many by many many factors. But what the paleontologists also tell us is the pretty extraordinary creatures have existed in the past. you know, if I mean, no one would believe that such that things such as dinosaurs could have, you know, could exist >> if if if our hillsides weren't littered with them, right? You know, an an amazing array of creatures, enormous creatures and things like this. And so, you know, there's lots and lots of wonderful things that aren't around anymore. Um maybe >> the sheer the sheer amount of uh what we what we fail to understand is the sheer amount of species that have been perished and that we don't have a count on them because they they didn't left us with fossil remains.
>> That's right.
>> Yeah. We we simple simply don't know.
>> Yeah. Yeah. It it it I love Darwin's uh early description, you know, that that the crust of the earth is a vast museum >> of which, you know, little has been explored and little has been, you know, retained. Um, nonetheless, you know, whether it's from Darwin's era or or much later, >> what paleontologists have on Earth has certainly taught us a lot about the the history of life and the history of our own species and and um you know, the great thing is that there's many many many more fossils still to be discovered. I think I still think it's a golden age of of paleontology. Um but it's hard work. It's hard work to find new things. Yeah.
>> And uh speaking of modern tools like um for instance crisper or prime editing which comes already in our hands.
>> How do you see experimental level de evolving in the next decade? So we're on the bridge of a very interesting era.
>> Yeah. Well, I think uh I mean let's just take Crisper for an example. Um it was so this ability to make very precise genetic changes.
Um it's a it's a very powerful way to test our hypotheses about things that have happened and sort of some of my favorite applications.
Uh there's this beautiful puzzle in nature uh discovered by a contemporary of Darwin discovered by Henry Walter Bates referred to as mimicry or Batesian mimicry. And this is where uh an unrelated spec species independently resembles another species and that's because of selective pressures in the environment to to to look similarly. And this might be for example butterflies that resemble each other. And mimicry it's it's a spectacular phenomenon and you can find it all over the world. But the butterfly mimicry is sort of a special case. It's it's spectacular.
It's kind of how it was first discovered with with baits. And it was in you know once once crisper came about our ideas about mimicry became instantly accessible with experimental tools as as people had some some leads to the genes that were involved. Now people working on for example butterfly wing patterns can manipulate those patterns on a on a daily basis using like crisper tools. So beautiful and important evolutionary questions are accessible because of these tools. Um, and you know, there's lots and lots of clever people both using those tools and and inventing and and and modifying new ones. So, I think there are certain puzzles in evolution, the origin of structures, things like mimicry that are hard to get at, but these genetic tools, the precision of these genetic tools allow us to manipulate things and to make very to test hypotheses very very um with with pretty high precision. And so I think that's what I see, you know, coming in the in the in the next years is I think a lot the other thing I would say about these genetic tools is they allow us to work on virtually any species.
>> So decades ago, if you were going to, you know, the most biological work was probably done on six or seven species. It was done on E.coli bacteria and brewer's yeast and arabidopsis and Drosophila, the fruitfly and and mice. Well, these and and that and part of that was because classical breeding techniques had been used on all of these creatures.
Now, we don't need to use classical breeding and we could just we can study organisms from the wild and we can study things that no one studied before. So, these genetic tools make accessible to us essentially the entire biosphere. And um that's very powerful evolutionarily that you're not restricted to just the seven or eight organisms that people have been working on for the most decades. you can, you know, jump into something that no one has studied before and and and do, you know, pretty sophisticated things.
>> What about the uh uh speaking of sophisticated things? I uh uh it just jumped in my mind the experiments of Jack her. So he wants to build, you know, of course he wants to be to build so-cal chicken. No, it was what what was >> or dino chicken, whatever you want.
>> Dino chicken. something like that.
Something like that. And he's he's pretty much on on this way. So, >> shall we have to expect something like mini Jurassic Park or mini Velociraptor in our houses?
>> I I think it's reasonable. Um, you know, okay, I'm gonna I'm gonna just do something before I answer that question. because of my age.
I I would say I I cannot it's it it's blows my mind what has happened in biology over the course of my career.
The the puzzles that were black boxes that nobody knew how to get into that have just been blown open. The genomes, you know, we routinely sequence genomes of complex creatures, you know, at at the um blink of an eye. Um, so it's very hard to predict except for the prediction that most things have gone faster >> and more and progress has been made faster than almost anyone predicts.
>> Yeah. So yeah, I think you're going to see more and more resurrection of extinct features, whether they're the full creatures, but you know, people are working on like the extinct dodo or people are working on trying to bring back the woolly mammoth. And just the challenge has to do with well just how much genetic information do we have about the extinct creature and what surrogate can we use to sort of bring it back? Can we use modern elephants to help, you know, gestate a woolly mammoth? I don't know what we're going to do about I mean, dodos. We're going to have to find um you know, some way to modify an egg and and try to make a dodo. Um and and then, you know, if you want to make a a more dinosaur like bird, uh yeah, start with a chicken and and and and and start to work in these traits. And you know it this may sound a bit like yeah a little like J Jurassic Park a little bit like scientists just being silly but it's this exploration that often it it necessitates the invention of new tools and things and then those have wide uses. So I think sometimes these really hard problems of you know bringing back an extinct species or whatever we can get a little agitated of oh is this a good use of money and da da da but usually it's just it's just an idea it's it's an inspiring idea that galvanizes a lot of thinking that then has its own sort of benefit. So there's a there's a saying I love it over here from uh uh I guess it was from a book done maybe in the 30s or something like like the usefulness of useless knowledge >> right so it might some things may sound useless or may sound like scientists are sort of you know off off a little bit uh off off the trail but it it so often spurs creativity and invention that becomes very widely useful. So yeah, I think there's going to be efforts to bring back extinct species or to bring back traits of extinct creatures in in modern animals. I don't think we're going to do big large scale ecological experiments with these things. We got enough ecological concerns with everything that exists in the world, but I think we're we're exploring our ability to uh manipulate genes and generate traits.
And I think that's probably going to wind up, you know, being of of medical use sooner rather than later.
>> Well, we we uh uh unique as a species because we can um manipulate our own reproduction. when when I taught my students about let's say development of mammals I asked I I start the lecture with a question uh what is the type of reproduction and what is the type of uh let's say um insemination in mammals and they say internal of course and I'm asking okay and what about external no what about in vitro soh okay yes so um We we've gone so far. But if you have to let let's let's put it that way. If you have to update now endless forms most beautiful, what new discoveries or perspectives would you be excited to to include to put in? Well, I think I would include some of these classic evolutionary mysteries that we now understand better, particularly the origins of structures.
>> Yeah.
>> Say something like the origin of the of the vertebrate limb that we now have a a lot of um you know, that's a that's obviously a really important structure to us. Phenomena like mimicry >> um that we now have a and it's rich.
It's really beautiful the when you look under the hood at at what's going on in mimicry and and again you see you know some of the same old genes doing new things right so it's it's something I think that I express in endless forms that we were beginning to see in those early days that you know invention is often a matter of teaching old genes new tricks well we've seen a lot more examples of old genes learning new tricks and that gives us I think a richer picture of where the you know diversity of life comes So I I think I would I would I you know just to make it still readable I would pick some beautiful fascinating phenomena around origins or mimicry. I would say maybe some examples of convergence as well. It's so fascinating to see independent lines of creatures arrive at a similar solution and to ask whether they took the same exact path or totally independent paths to that. Um, so I I think I would those are those are classic mysteries that naturalists have worried have wondered about for ages and I think Evo DVO has has uh shed light on them. I that's what I'd pick.
>> Well, great idea. So um um I can't skip the question about astrobiology. What are the lessons from Evo Divo that can be applied in there? because you know I still believe that within our lifespan we will have to face the question of let's say not even encounter with with the life outside of the borders of our planet but at least with the fossil records of that life and I'm >> I'm assuming those findings on the Jezero crater also um the future missions like Europa Clipper like this dragonfly a um mission which hopefully will be sent to to to >> well I think this is a you know partic we'll get to the lessons of Evo DVO in a second but just sort of say for humanity this would be one of the most exciting discoveries of all time is that you know I know that most of lot most scientists think there is life out there in fact some people may think as I do that it might be very abundant widespread microbial scale. I'm not saying it's all giraffes and redwood trees, you know.
Um, but you know, we've had for all of humanity's existence a very earth ccentric view of life, right? And and we've and we like to ponder the existence of life out there. But if we really confront its existence and its history, that's tremendously exciting.
I think that the lessons of evo devo for astrobiology aren't really different than the lessons of evolutionary biology in general, which is I think some of the rules of evolution are going to apply throughout the universe in that uh if if life is a is a form that replicates and there's variation in those replicating forms, then natural selection is going to operate and there's going to be lineages, right?
there's going to be ancestors and descendant relationships in those in that life. So much of what we've discovered about sort of the general rules of evolution, I think, are going are going to apply out there in the in the universe and that, you know, we we things things will probably speciate and uh things will have changed over time and uh but I do I do expect that life is is going to be more microbial, more cellular as it was for the first three billion years on on Earth. you know, visit visit Earth for most of its history and life would be small and microbial. I think that's what we're going to find out out there in um in the universe. And I I I hope I would love to see con, you know, really concrete evidence in my lifetime because I think it would be one of the most exciting discoveries that humanity could ever make.
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