004 - Witness the fitness

Kat: Hello, and welcome to Genetics Unzipped - the Genetics Society podcast, with me, Dr Kat Arney. In this episode we’re taking a dive into the world of evolutionary genetics to witness the fitness - we ask whether street smart city-dwelling birds are genetically different from their country bumpkin relatives, how butterflies got their brightly patterned wings, and if today’s genetic research would have blown Darwin’s mind.

First up - what do these three things all have in common? Sonic Hedgehog, Scott of the Antarctic and Swiss Cheese? They’re all the names of genes or mutations, and they’re all featured in Genuary. Every day throughout January the Genetics Society will be tweeting about a different gene, so follow them at @gensocUK to get your fix of genetic fun, from Armadillo to Van Gogh.

Witness the fitness

Kat: Back in November I took a trip to Exeter for the Genetics Society Autumn meeting - From Genotype to Phenotype to Fitness - exploring how an organism’s underlying genetic makeup - its genotype - affects how it turns out (that’s its phenotype), which in turn affect its chances of survival and reproduction in the world, or its fitness.

Charles Darwin summarised this idea back in 1868, writing “The power of selection, whether exercised by man or brought into play under nature through the struggle for existence and the consequent survival of the fittest, absolutely depends on the variability of organic beings. Without variability, nothing can be effected.”

To find out how researchers at the meeting are putting Darwin’s theory to the test 150 years on, I caught up with one of the organisers, Professor Alastair Wilson from the University of Exeter, during a rather noisy coffee break.

Alastair:  Broadly speaking, it's an evolutionary genetics meeting - everybody here is interested in evolution. But we wanted to make the phenotype - the set of traits expressed by individuals whether they are animals or plants or whatever - we wanted to put that in the centre of what we were thinking about. I suppose that comes from being evolutionary biologists as well as geneticists. We are interested in natural selection, and natural selection acts on traits, right?

So, although we're all focused on what's going on with genetics and how new genetic technologies can help us, ultimately, we've still got to think about phenotypes. And if we want to understand evolution or at least adaptive evolution by natural selection, it's all about how the genes influence the phenotype, ultimately, because it's the phenotype that then influences fitness.

Kat:  Obviously, because a gene is just a length of DNA; it needs to be expressed, it needs to make something, it needs to then have cells that make a body or an organism and do stuff. And that's what evolution acts on. It's: how does this organism interact with its environment and what is it responding to?

Alastair:  Exactly. It's doing stuff. It's the point at which the organism is interacting with the environment, and what the consequences of that are for whether it can reproduce, how much it can reproduce, whether it can survive. But actually, interestingly, you said a gene is a bit of DNA. Well, it is, but before it was a bit of DNA it was also a unit of inheritance.

One of the things we've got in this meeting is we've got all different types of geneticists. Some people are studying bits of DNA, some people are editing bits of DNA, but we've also got geneticists in the broader sense who are using more statistical approaches to study how traits are being inherited in populations, sometimes with no molecular data at all, using pedigree-based approaches and relatedness - sort of classical, quantitative genetic approaches.

So we've got everything from molecular genetics through genomics, population genetics, and also basically, evolutionary ecology. And there's lots of ecologists here as well as geneticists, so it's sort of crossing the boundaries a little bit.

Kat:  What sort of themes are the talks going to cover? What kinds of things are we looking forward to hearing about?

Alastair:  Very broadly, we've put the talks into four themed sessions. The themes are very porous, and we are already seeing that people are straddling multiple themes. But the first one we are having is Genotypes to Phenotypes. This is perhaps the most obvious thing you think about when you think about evolutionary genetics - is okay, how are those phenotypes built? What is the way in which genotype maps to a set of traits that are expressed? We heard about that this morning.

Then we're moving into a session that's about Conflict and Constraint, because one of the things about natural selection is it doesn't act on single traits in isolation. So actually, if we make genetic changes or genetic changes happen, then there can be multiple phenotypic consequences, some of which may be good for an organism, some of which may be bad. So, lots of the way we understand phenomena like parent offspring conflict, intersexual conflict and things like that, actually come down to the idea that there are conflicts within the genome in terms of their effects on fitness. So, some things are good, some things are bad.

After that, we are moving into a session that we've called Genes in the Environment, and that's really where we're starting to bring in some of the ecology, because it's all very well trying to understand what it is that a genotype does in terms of affecting a trait in some sort of laboratory system but actually, does it cause trait variation in the wild? Because that's really where selection happens.

Then the final session that we're going to do is called Micro to Macro, and we're moving from thinking about how traits evolved within populations, for instance with selection acting on genetically variable traits, to seeing whether we can use patterns of differences among species, thinking about speciation and hybridisation genetics as a way to understand evolution.

Kat:  We've seen a few talks this morning and one of the things that really jumped out at me was the idea of making really quite small changes in the control switches - the regulatory elements that turn genes on and off – and that they can make really quite big changes in organisms. It's always struck me, when you talk to people who are like, "Well, evolution, it's really difficult to see how it works because if you make tiny changes in DNA, how do you make a big change in an organism?", and I found that really striking.

Alastair:  Yes, I'll be honest, I did too. I think we started with the last talk that was about plants, and also earlier that was presented on butterfly wings and patterning. It's really striking that you can have these sometimes relatively small numbers of genes of major effect.

It's striking to me in part because actually, I do come from that other camp. I come from the camp where I study traits that for the most part we think of as probably being down to loads and loads of genes with small effects. So I think it's an eye-opener to me because it rocks my world view. But that of course is why we're here, right? To kind of challenge each other's viewpoints.

I think what it shows is we have to be open and alive to the possibility of all kinds of genetic architectures underpinning traits. And of course, actually, that structure of the genetic architecture; how many genes there are, where they are distributed, whether they have big effects or small effects, that really feeds back to impact the dynamics of the way traits evolve under selection. So, it's all good stuff, really.

Kat:  And it really is evolution's playground, isn't it? I love all the different variations you can get by making small changes or making small changes that have very big effects.

Alastair:  Yeah, absolutely and the genetic technology is just incredible, that we have now. So that's super exciting. There's a place for that, but there's also a place for - actually, we still need the field biologists, because we want to understand this. There still need to be people out there looking in nest boxes and measuring birds or whatever it might be, whatever the organisms are. We can't do evolutionary genetics just by manipulating genomes. We have to be doing everything. We have to be doing everything from studying DNA and manipulating DNA, right the way up to doing field biology still. So, it's a wide spread of activities.

Kat:  And finally, and very briefly, it's now 150 years or more since Darwin published On the Origin of Species by Natural Selection. What do you think he would think if he was at this meeting today?

Alastair:  Ah, yes. Trick question! I have absolutely no idea. There's always a quote you can find from Darwin that seems to suggest he has thought of everything. I hope he would be enthusiastic. I hope he would be impressed with how people have taken his ideas and interpreted them. But of course, Darwin knew nothing about genetics as well, so this would be a whole new world for him, so I hope he would be pinning his ears back and learning as much as he could.

Kat:  I imagine if he was on Twitter he would be posting like, "Mind: Blown!"

Alastair:  Yes, exactly, yeah. Which is kind of what I've been doing as well this morning!

Kat:  That's Alastair Wilson, from the University of Exeter.

To pimp a butterfly

As Alastair mentioned, one of the first talks we heard at the meeting was on butterfly wings. If you’ve ever taken a trip to South America - or even to a butterfly house in a less exotic location - you’ve probably seen examples of Heliconius, also known as passion-vine butterflies, with their brightly coloured and dazzlingly patterned wings.

There’s a huge number of species of Heliconius living throughout the New World and up into the southern United States, and each one of them has its own genetic and evolutionary story to tell about how it got its particular pattern, as I found out when I chatted to Chris Jiggins from the University of Cambridge.

Chris:  Well, they've been studied way back since the days of Darwin, and they were sort of showing off to predators because they're bad to eat. So they're very visually attractive and beautiful and quite easy to catch.

Then they also have lots of mimicry, so they attracted the attention of early evolutionary biologists such as Henry Walter Bates, who noticed that there were lots of different species that evolved to look the same. Really, it was studying these South American butterflies that led to the theory of mimicry.

Kat:  Just describe to me what some of them look like? If we had a few different species here, what kind of patterns and wonderful colours would we be seeing in these butterflies?

Chris:  They have very bold patches of red and yellow on a black background, typically. They're very simple patterns. There are bands and stripes, they use the classic warning colours of bright red, bright yellow.

Kat:  What do we know, then, about the genes that are involved in making these patterns? If you say that several different species who are genetically different have managed to get the same patterns, what is going on there? What is going on at a genetic level, to give them these patterns? And then how they've evolved this similarity?

Chris:  What we've found, really, which is kind of remarkable, is that there's this amazing amount of diversity of different patterns in all these different populations and species, but the more we study this diversity, it all seems to boil down to, basically, four genes that have very large effect. There's lots of different alleles in different populations that control the expression of these genes and produce all of this amazing diversity in wing patterns.

Of all the hundreds of genes that must be involved in making a wing, it seems to be again and again just a small number of them that are picked out by evolution to change when you evolve a new phenotype.

Kat:  That's kind of weird, because from what I know about genetics, even something as simple as the number of fingers you've got or height, or all of these things - there's loads and loads of genes and loads of tiny little variations in them that all add up. It's kind of weird to find just four genes gives you this incredible multitude of patterns.

Chris:  Yeah that's right. So yes, some traits like height or growth seem to be controlled by many, many genes of small effect, but other traits that are important in natural populations, we find this pattern of just a small number of genes with large effect. I guess these wing patterns of these butterflies are at the extreme end of that. They are incredibly diverse, but all of that diversity is controlled by a small number of genes with very large effects.

Kat:  So, let's drill down into this a little bit more. When you actually look at these four genes, what makes the difference between a butterfly with one kind of pattern, and a butterfly with another kind of pattern? Is it a change in the actual gene itself? What's going on?

Chris:  We think it's all changes in the DNA sequence of non-coding DNA, next to the gene (the bit of the DNA that makes the protein). So it's actually not changing the protein - the product of the gene, it's changing the instructions that tell it where and when to be expressed. So by expressing these genes in different patterns across the wing, in different places in the wing, you can produce these different patterns.

As you develop an organ, there is a complex network of genes that tell cells where they are, essentially. Are you at the top bit of the heart or the bottom of the heart? A wing is the same. There are these genes that tell cells where they are in the wing, and what sort of development pathway they should go down.

So, the patterning genes can lock into that information that's already there, specifying the geography of the wing and turn on in different combinations to make different patches in different places on the wing as it develops.

Kat:  When I think about that, say when you think about a computer programme, if you were going to use a computer programme to design something, you are effectively tweaking the parameters then. You're effectively saying - let's have a bit more of this here, and then a bit less of this here and then okay, here's this gene, let's have more of this here and a bit less of this here.

Chris:  Yes, exactly. Your genes are regulated often by transcription factors and so you can alter the binding site for that transcription factor so it binds more strongly or less strongly, and that turns that gene on in that particular patch, or turns it off, as the case may be. If you do that in the right combination then you can turn on a big red patch on the tip of the wing or you can turn it off again.

Kat:  These butterflies caught the attention of biologists because of this mimicry, the fact that you get genetically different species that look the same. When you start delving into the genetics and what's going on, do you find that these species have got to the same place through similar genetic changes?

Chris:  Yes, absolutely. That was one of the first things we showed, that the mimetic species actually used the same genes to make their mimetic patterns, and sometimes they do that by reinventing the wheel - they'll evolve the same switches or similar switches in the same place in the genome independently, in different populations.

Sometimes, they do it actually by stealing variation from their relatives, so hybridisation between closely related species can mean that genes can pass between species. That means that the selection to mimic a species that's nearby - you might actually do that by stealing the genetic variants from your neighbouring species.

Kat:  Go and breed with it, rather than evolving it yourself, you lazy butterfly!

Chris:  Exactly.

Kat:  What's the next thing that you want to understand about these beautiful butterflies? It's lovely to say, okay, we've found just four genes and by tweaking the regulatory dials you can get this incredible array of patterns, but what do you want to know next?

Chris:  One of the things we have found out already is that you can take existing variation and shuffle it into new combinations in order to produce diversity. You can produce new combinations of patches by taking existing genetic variation and putting it together in new combinations. So even very close little pieces of sequence in the genome can be recombined to make new combinations. That's one thing.

But we still don't really know, within those little regions of DNA - we know that it contains the instructions to make that patch on the wing. We don't really know what genes it's interacting with and how many changes you need. How many changes in the DNA does it take to make a new patch on the wing?

We haven't really figured that out yet, and that would be interesting to know if we are thinking about how difficult it is to evolve a new pattern. We'd like to know how many changes are involved. Are they changes of sequential small effect, or is there one DNA change that makes that big new patch on the wing. So dissecting actually down to the individual base pair changes would be one direction that we go in.

Kat:  Chris Jiggins, from the University of Cambridge.

Urban evolution

Kat: Most of the talks at the Autumn meeting were about populations of organisms living in the wild or in closely monitored laboratory conditions, from Chris Jiggins’ South American butterflies or the dazzling array of closely related cichlid fish species found in African lakes to the sexual predilections of strange stalk-eyed flies living in a lab in London. But, as I discovered when I spoke with Anne Charmantier from CNRS in Montpellier, France, evolution is at work in the heart of our urban environments too.

Anne:  Actually, I started out by being this field person that goes out in the wild and in the forests. This is the way I envisaged to study evolution was to study it in the wild. Actually, until recently I never really thought about studying evolution in cities until I read studies on how a lot of people that are investigating phenotypes in cities are finding that birds - because this is what I work on - but also many other taxa differ in many different traits when we measure them in cities compared to when we measure them in the wild.

Kat:  I've heard stories about this, that the city birds have really loud voices, or they sing in different ways so that they can be heard over cars and sirens.

Anne:  Yes, that's I guess one of the most obvious things we can measure, is the volume of the song. But there's also song complexity and also many other traits. Basically, almost every trait that we have looked at in birds in the city differ from the forests.

This was kind of a surprise initially, and also because I've been working for a long term on how environmental heterogeneity in the wild affects phenotypic evolution, I discovered that contrasting forests with city birds gives actually very strong results compared with what we can find in the mosaic of habitats that birds inhabit outside the city. That's what got me excited, to realise city birds are so different in so many ways - I want to understand why!

Kat:  So, if you're saying that a bird - say you took a bird from a mountain area or a forest area, they would be more similar than these weird, streetwise city birds that you're studying?

Anne:  In many ways, yes. So, for example, we are studying personality of birds, and we are finding that birds in the city behave very differently for many species than they would behave outside of cities. Of course, because they are habituated to humans, but also it's more complex than just that. They are usually more aggressive but they also explore their environment in very different ways. Of course, our evolutionary mind brings us to think that this is probably an adaptive response to the urban environment, which is what we are trying to test, basically.

Kat:  Cities and the way we understand them now, there have been big towns and cities for thousands of years but not in the way that we have them now in the 21st Century. How are animals keeping up and adapting to the modern city? What are some of the things that you find most interesting, and the kinds of challenges that these organisms are up against?

Anne:  Yes, this is a very good question. For example, studies are flourishing on pollution, and how animals are adapting to pollution. I think you've actually put your finger on a very interesting feature of cities, that some cities are very old and other cities or other areas of cities are much younger.

This is where I see a huge opportunity that we can compare very old cities to much younger cities or much older areas of cities to much younger areas. This is something I want to do in the future, but it's really very novel. We don't yet have the background that can tell us exactly what differs between old cities and new cities that the animals would have adapted to, but I think there's a huge potential there.

Kat:  And obviously, some organisms will be born or grow in the city where their parents were, but some will come from outside and they will move from a rural environment and come to the city as humans do - let's go and seek a job and a new life in the city. Do you think there's a difference between the kinds of birds that are like, "No, I want to stay in the countryside", and the sort of birds that are like, "I fancy the bright lights?"

Anne:  I think there is. I'm pretty sure that there is non-random dispersal, non-random gene flow between natural habitats and urban habitats. This is kind of what convinced me to take the genomics approach on this project, to try and figure out population structure but also the direction of gene flow, which is something we are still working on.

I do believe that some individuals are already better adapted to the city environment than others. This is true for humans as well. I'm also interested in that, really, what is the variation that predetermines whether a bird will decide to make a home in the city or not? Hopefully the genomics will tell us this story.

Kat:  And finally, evolution is something that we tend to think of as acting over hundreds of thousands of years, but the kinds of cities that we are seeing have really grown in the past hundred years or less. Studying evolution on that incredibly condensed scale - what are some of the challenges, and how do you actually see what's evolving on that kind of compressed scale?

Anne:  So, on the short scale that we are looking at, it is possible that we will see a lot of plastic response and that it is going to be more difficult to see evolutionary response.

Kat:  By that you mean it's organisms changing their behaviour but not necessarily showing in their genes?

Anne:  Exactly, yes. Obviously, when birds arrive in the city environment, if they are lighter and smaller, it might just be because they are not as well fed as they would be in a natural forest with lots of insects and lots of caterpillars. So, there's bound to be plastic responses and I'm also interested in that, actually, and plasticity itself can evolve. It is trickier to demonstrate genetic evolution than it is to witness plastic responses to a new environment.

But what we do think is that the urban environment is so different compared to more natural places, that the selection pressures in the cities are very strong for certain traits like behavioural traits or reproductive success. We do think that this selection is so strong that evolution might happen in just a few generations and that we might witness it.

Kat:  So actually, you're saying you could end up with, say a city species that can no longer interbreed with the country species? Do you think we could start seeing that? City birds that will have nothing to do with their country mates, they won't hang out with them, they won't interbreed with them, and effectively they are a city species?

Anne:  On the species I'm studying, for the time being we are talking about ecotypes. So morphotypes and ecotypes, because we know that birds are different but they still interbreed very easily. Of course, it might be the first step to speciation. It's going to take a long time before we witness that, so maybe studying microbes or other types of organisms that have a much shorter generation time will be better if we want to witness this type of speciation event in cities.

Kat:  That's Anne Charmantier from CNRS in Montpelier, France.

Meet the president

Kat: 2019 is the Genetics Society’s centenary year and there are events planned across the whole of the UK and online to celebrate. It’s also a year in which we have a new president - Professor Laurence Hurst, from the University of Bath. He was at the autumn meeting in Exeter in his scientific capacity as an evolutionary geneticist, but I took the opportunity to nab him for a chat about his priorities for the Society over the coming year and into the future.

Laurence:  Historically, the Genetics Society has been one of these wonderful forces for good for the community of geneticists in the UK, but more broadly as well. There's no reason to disturb that. That's a great ongoing project.

What I would like to see is encouragement of early career researchers, that's again something that the Genetics Society is very, very good at. That would also include, I think, a shift maybe away from just an academic focus, to also incorporating commercial genetics a bit more. But also, opening up other possibilities to our early career researchers. There's very much an idea that you do a PhD and a post doc and a post doc and then a lectureship, but there are many other careers in genetics.

I would like to be bringing the industrial genetics in a bit more, opening up these avenues to our early career researchers as well, but in the background and in the context of doing what the Genetics Society has done incredibly well all this time.

Of course, it is such an exciting time to be a geneticist. I don't think there's ever been a better time. We're a hundred years old, so it's a very young science in many regards. If I tell you that of all data ever collected by humans over the entirety of human history, 90 percent of it was collected in the last two years and nearly all of that is gene sequence data. We are in a second industrial revolution and it is a genetics revolution, so I think we need to be at the forefront of helping and encouraging what we do with all of this data.

I think the Genetics Society can be really key, because the Genetics Society is unusual because we do represent everything from molecular and cellular biologists and molecular geneticists, but also; transmission geneticists, quantitative geneticists, population and evolutionary geneticists. Now is a fantastic time for these folk to talk to each other.

I think there are really important dialogues to be had for example, between the evolutionary geneticists on the one hand and the cancer geneticists on the other hand. Those sorts of interactions can be mediated by the Genetics Society and have been done very successfully in the past, and now is a fantastic time to be doing it - the opportunities are enormous.

Kat:  This is the Genetics Society podcast. One of the important things for me, as a science communicator and a former geneticist, is about communicating this incredible science to the public. How do we understand genetics? How do we talk about it? What do you see as the Genetics Society's role for communicating this complicated but really exciting science?

Laurence:  Well, let me start off by not answering that question, and answering a different one. I'm actually very, very keen on the notion that education is the most powerful drug that we have. Like any drug treatment, what that means is that we need to know how to administer the drug effectively.

Although I am a classical geneticist and evolutionary geneticist, we actually do very large in-school trials, working out how to teach evolution, how to teach genetics. We've shown that you can do it very successfully in primary schools, for example. Both genetics and evolution can go in.

Now, into that context, the Genetics Society can have a really important role. One thing I'm really delighted about is that in this centenary year, the Genetics Society will be providing really quite a lot of money for public engagement. That also means grants for public engagement. While normally our public engagement grants are of the order of £500, and with that you can do a lot of good, we are now moving to a scheme where you can apply to up to £1,000, or for something more ambitious, for £5,000.

So in principle, you could do really good trials of not just going out and doing public engagement, but also work out how best to do public engagement. It does tend to be something that is very much led by enthusiasm, but not necessarily with a good scientific base, to say actually, this is the best way to do it.

What we do know from that literature, is that there are ways of doing public engagement that can actually be damaging. There are ways that are incredibly good but you can really put your foot in it if you don't know what you're doing. That being said, I've yet to meet any case where a geneticist goes into a school and simply enthuses about their subject, and that enthusiasm is not simply infectious - I mean it really is!

We see for example with some of the trials that we do, that one day's well-thought through engagement with primary school pupils is life-transforming for the primary school children. So I think yes, the Genetics Society is really well placed to take this banner of public engagement and use the centenary as a bouncing point, as it were, to enable that.

Kat:  So, the Genetics Society is a hundred years old this year. I'm always aware of the problems of asking people for this sort of future gazing, but where do you think the direction of travel is heading for the next hundred years? Obviously, you might not be president for the next hundred years, but where do you see the direction of travel heading?

Laurence:  That's such a hard question, it really is. Who was it who said that prediction is really hard to do, especially if it's about the future? Whenever I think about a question like that. I think I really ought not to comment because I will simply get it wrong, but it's almost inevitable that we are going to see evermore genomic data.

What I would hope for but not necessarily expect to see, is a much better integration between our various strata of genetics. There is so much to be gained from molecular geneticists talking to evolutionary geneticists, talking to quantitative geneticists. Also getting genetics out to the public, but also genetics into the industrial workplace as well.

Kat:  So, roll on the next hundred years?

Laurence:  Yes, and I will most assuredly not be president. There's a prediction I will stand by.

Kat: Professor Laurence Hurst there, certainly not making any promises!

Finally, you can still watch the fantastic Royal Institution Christmas lectures on iPlayer, in partnership with the Genetics Society and featuring the fantastic Alice Roberts, Aoife McLysaght and Fran Scott - all of whom appeared in the very first episode of Genetics Unzipped to give us a sneak peek behind the scenes.

For more information about this podcast including show notes, transcripts, links, references and everything else head over to geneticsunzipped.com You can find us on Twitter @geneticsunzip or email us at podcast@geneticsunzipped.com with any questions and feedback. Please do take a minute to subscribe on Apple Podcasts or wherever you get your podcasts from, and it would be great if you could rate and review - and more importantly, please spread the word. Tell your friends, send out a tweet, and share the love.

Genetics Unzipped is presented by me, Kat Arney, and produced by First Create the Media for the Genetics Society - one of the oldest learned societies in the world dedicated to supporting and promoting the research, teaching and application of genetics. You can find out more and apply to join at genetics.org.uk  Our theme music was composed by Dan Pollard, and the logo was designed by James Mayall. Thanks very much to the brilliant Hannah Varrall for production, thank you for listening, and until next time, goodbye.

Heliconius image from Repeating Patterns of Mimicry. Meyer A, PLoS Biology, Vol. 4/10/2006, e341 doi:10.1371/journal.pbio.0040341 CC-BY 4.0