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Down the Rabbit Hole: Conservation Genetics and the Tasmanian Devil – Paul Hohenlohe

Paul Hohenlohe is an Associate Professor in the Department of Biological Sciences at the University of Idaho. Hohenlohe’s research focus is on the genomic architecture of evolving populations. He uses the power of modern genomics tools to address basic questions on evolution, conservation and cancer.

Please note the transcript has been edited for brevity and clarity.

FLG: Hello, everyone, and hello, Paul, thank you so much for joining me today as we go down the rabbit hole and take a look at some of the unusual aspects of where genomics is being applied. Today we’re joined by Paul, who is a researcher exploring evolutionary and conservation genomics. So, Paul, if you could just introduce yourself, and tell us a little bit about what you do.

Paul: Yeah, it’s nice to be here. My name is Paul Hohenlohe. I’m an Associate Professor at the University of Idaho in the United States. And I work on evolutionary genetics and genomics and conservation genomics.

FLG: As I mentioned, we’re going to be talking about conservation genomics. Would you be able to give everyone a brief overview of what that is exactly?

Paul: Yeah. So, conservation genetics, or conservation genomics, is basically using the molecular biology tools of genetics and genomics that biologists have been working on for decades and applying them to questions of conservation of rare and threatened species and biodiversity around the world. And so, we can talk about a number of different ways that genetic tools can be applied to address conservation related questions.

FLG: What is the importance of this area of research and why is it becoming so relevant in society today as well?

Paul: Well, I would say that genetic tools have been used in conservation for a few decades, at least. Going back to the 1970s and 1980s, we started to develop tools to understand genetic processes in natural populations of plants and animals. And even since then, we’ve been using those tools to address conservation questions. The change in more recent times has been just the technology for genetics and genomics, so our ability to get massive amounts of DNA sequence data, for instance, has really revolutionised what we can do in the whole field. And it’s changed a lot of the sorts of questions we can address in conservation situations.

FLG: What are some of the main questions that are being explored at the moment?

Paul: Yeah, so some of the main uses of genetics and conservation are to identify populations and distinguish different populations. For instance, different populations of animals across a landscape living in different places. We can use genetic tools to ask how different those populations are, whether they’re connected in terms of exchanging individuals. We can use genetic tools to identify species, but also identify individuals. So, for instance, there are a number of genetic tools we can use to identify individuals without even capturing them. So individual animals, we can identify with hair samples or faecal samples, so-called non-invasive genetic sampling, which opens up a whole range of ways to track individuals across the landscape and identify parents and offspring and really get detailed information about populations of wildlife.

FLG: How have the genomics tools evolved over time and allowed us to look at these different types of samples and delve even more into different populations?

Paul: Yeah, the technology has really changed quite a bit. So, as I mentioned, one of the main aspects of that change has been the ability to produce DNA sequences. If you think back 20 or 25 years ago, and we talked about sequencing the human genome – that was in the 1990s – that was a massive effort involving large numbers of people, large amounts of money and equipment. Nowadays, that same amount of genetic information can be produced for a remarkably tiny amount of money on a desktop computer, that sort of thing. So, the amount of data that we can produce has really changed, but also other techniques for, like I said, getting non-invasive samples. So, for instance, gathering DNA from hair that’s left behind by a wildlife individual, or even gathering DNA from environmental samples. So, for instance, taking a sample of water from a stream or a lake, extracting DNA from that, sequencing the DNA and being able to identify what species are present. Those sorts of techniques have continued to advance also.

FLG: What are some of the main genomic tools that you’re using in your research?

Paul: So, we use a few different genomic sequencing tools. One of them is called RAD sequencing, which stands for restriction site-associated DNA sequencing. Essentially, it’s a technique to sample genetic information from a number of individuals. And it gives us information about not the entire genome of those individuals, so not all of the genetic information for those individuals, but usually tens of thousands of locations across the genome. So, we can sample tens of thousands of genes or regions of the genome across a set of individuals. And one advantage to that technique is that we don’t need any prior information. So, we could go into a jungle and discover a species that’s never been studied before and apply the sequencing technique right from the start and gather that sort of information. The other technique that we use increasingly, because it’s becoming increasingly inexpensive to do so, is just to sequence the entire genome of whatever individuals we have. So, it’s becoming more and more reasonable to be able to get the entire genome sequence for a set of individuals in a conservation study on a modest research budget.

FLG: How does your research within conservation work alongside the research that you do within evolutionary genomics, and how do the two interplay?

Paul: So, a lot of the questions are basically overlapping, or similar questions that we might ask in those two. One thing that the modern genomic techniques have allowed us to do is to understand adaptation. So, populations living on a landscape or living in the ocean are adapted to their local environment. With genomic tools, we can understand that at a DNA level. And we can use the genomic sequencing technology to get really detailed information about that sort of adaptation. So that gets us to basic evolutionary questions about how populations and species adapt to their environments. But that’s also a whole new area of conservation genetics, where we can ask, for instance, whether populations are adapted to their local environment, or how different they are from other populations. And that can help guide conservation and management efforts, if we know how much of a role adaptation is playing.

FLG: Why is studying evolution so important? And how does that impact human health and disease?

Paul: Yeah, so I think it’s good to point out that evolution is the central process in biology in terms of structuring the way that animals and plants and populations change over time and are adapted to their environment. So evolutionary processes feature in a lot of things that we would care about. So, everything from antibiotic resistance of bacteria that we’re concerned about, thinking about the different strains of the coronavirus that we’re still worried about cropping up in different parts of the world. That’s an evolutionary process. But then also in terms of conservation, thinking about, for instance, climate change or other environmental changes that have an impact on natural populations. One question we’re often interested in answering is, do these natural populations that we’re concerned about have the capacity to evolve and adapt to climate change or environmental change. So again, that’s an evolutionary process that we are asking about there.

FLG: How can genomics tools help you to predict that response, in terms of whether species will potentially survive or not as the environment changes?

Paul: Right. So, one of the more interesting aspects of conservation genomics, just in the past few years, is methods to address that very issue. So, one of the ways that we can do that is, for instance, imagine a species that is spread across a continent, say, a species that lives across most of Europe, occupies different habitats or areas with, for instance, different temperature or different precipitation. We can use genomic tools to ask how those populations are adapted to those different habitats. And we can identify the actual genetic variation that’s responsible for that adaptation. And then we can connect that to things like future climate change scenarios. So, we know that, for instance, some places are going to get hotter, and some places are going to get drier over the next few decades with climate change. By connecting those two, we can assess which populations have the genetic variation that they would need to adapt to future conditions, and also identify which populations may not have that genetic variation. So, in that case, we might think about moving individuals from one population to another to supplement genetic variation and allow those populations to adapt.

FLG: Could you potentially work in the past, in terms of looking at samples from extinct species or from ancient DNA samples, and looking at the genetics there and seeing why they potentially didn’t survive, whether there’s any genetic variation that made them not adapt well to that changing environment and then apply that to the present as well?

Paul: Yeah, that’s an interesting question. I think it’s hard to detect what’s not there. So, it can be hard to understand why, for instance, a population went extinct. But, as I mentioned, of all these technological advances in the world of genetics and genomics, some of those include the ability to get DNA from ancient samples. So that means animal specimens that have been in a museum for the last hundred years, or it means getting DNA from, for instance, mammoths that have been frozen in permafrost for 10,000 years. Our ability to get DNA and genetic information from those sorts of samples has really improved. So that can tell us a lot about what sorts of genetic changes have happened over recent time, over the last hundreds or thousands of years, in some of these populations.

FLG: You mentioned the woolly mammoth, and there are several de-extinction projects that are going on. In your opinion, what do you think of these projects in terms of the impact that they might have on current conservation efforts? Because obviously, we have species that are currently vulnerable, and funds are being distributed for projects that are focused on potentially reviving animals that we’ve already lost. In your opinion, what do you think about these projects, and should we just be focusing essentially on the vulnerable species right now?

Paul: Our technology continues to advance and so we can talk about these things that seem like science fiction, sort of Jurassic Park scenarios of bringing species back from extinction. But I think as far as conservation, those things are unlikely to play a major role in conserving natural systems and natural species. As much as we can learn about genetics and adaptation, we are very, very far from being able to, for instance, genetically engineer species to improve their chances of survival and that sort of thing. It’s definitely still the case that our main focus, in terms of conservation, should be conserving habitats, conserving populations where they are now, maintaining their genetic variation where they are now so that they can adapt to changing environmental conditions.

FLG: Part of your research is looking at the Tasmanian devil. Would you be able to discuss the Tasmanian devil and its conservation status and why you’re focussed on that particular species?

Paul: Right. So, the Tasmanian devil is a charismatic species. A lot of people may know it from the cartoon. And a lot of people may not know that it is actually a real animal! As of now, the Tasmanian devil is the largest marsupial carnivore since the Tasmanian Tiger went extinct about 100 years ago. So, the Tasmanian devil is a species that’s limited to the island of Tasmania in Australia. And the reason that they’re a species of conservation concern now, and the reason that we’ve been working on them, is that they suffered from a transmissible cancer, which we can talk about more what that sort of disease is. It’s a disease that has swept across the species range of Tasmanian devils and has had a huge impact on the population of the species. So, the total population of devils has declined by something like 80 to 90% as a result of this disease, and so that’s where the conservation concern comes from, is that this disease represents a real threat to persistence of the species.

FLG: Would you be able to discuss further about transmissible cancers?

Paul: Right, right. So, we think of a traditional cancer or typical cancer as being a set of mutations that happens in the body of an individual that then leads to uncontrolled growth of some group of cells or tissue and that produces cancer. And cancers can be caused by environmental factors, they can be caused by viruses that can be spread among individuals. But in the case of a transmissible cancer, what’s actually spread among individuals is the tumour cells themselves so the actual tumour tissue spreads from one individual to another, and then starts growing in that new individual. So, for instance, in the case of Tasmanian devils, the disease is called devil facial tumour disease, or DFTD. And DFTD first developed as a typical cancer in one individual female, sometime around the early 1990s. But then it somehow acquired the ability to transfer from one individual to another. So, all of the individuals that have DFTD now, those tumour cells are derived from that one original female back in the 1990s. And those tumour cells have been transmitted from one individual to another. So that’s how transmissible cancer acts, essentially, as an infectious disease.

FLG: How are you using genomics tools to study these transmissible cancers?

Paul: Yeah, so we are part of a large collaborative group working on this question. And there are other groups of researchers as well, using genomics tools in lots of different ways. One of the areas that we are focused on most is thinking about adaptation and evolution in the devil population. This disease has spread across the population and is having a huge impact. The one basic question is, can devils evolve in response to this disease? Could they evolve, for instance, some sort of resistance to the disease that would then allow them to persist? As I mentioned, we can use genomic tools to ask whether they are actually evolving in response to the disease. And that’s one thing we found is the answer is yes. Across Tasmanian devil populations, there’s strong evidence, at the genetic level, that they are evolving in response to the disease. And that evolution likely includes many, many genes across the genome. So, it’s not just one single mechanism of resistance. It’s potentially multiple different genetic factors that are playing a role.

FLG: What are you hoping to explore next?

Paul: So, there are a number of ongoing questions in Tasmanian devils. One of them, which is remarkable, is that a second transmissible cancer was discovered just a few years ago in Tasmanian devils. So that means that although there’s maybe half a dozen transmissible cancers across the entire animal kingdom, Tasmanian devils have two. Part of the reason we know that is because, like I said, the first one, DFTD, originated in a female, and so all the tumour cells of DFTD have two X chromosomes, even if the tumours growing on a male. The second transmissible cancer in devils originated in a male so they have evidence of an X chromosome and a Y chromosome. So, for some reason Tasmanian devils are susceptible to transmissible cancers in a way that virtually no other animal species is. So, we’re certainly interested in, and other are researching, why that could be and what makes them susceptible to this disease. But we’re also interested in asking whether devils are adapting and evolving in response to this second transmissible cancer. We’re beginning to learn that as that second transmissible cancer expands and is spreading across the local devil population. The whole other side of this research involves genetics and evolution at the level of the tumours. So, one thing that we’ve been able to do, and others have done, is conduct genetic sequencing of large numbers of tumour samples and use that to reconstruct aspects of the spread of the disease. So, to understand some of the dynamics of how the disease spread across the devil population in ways that are better. Similar to what people are doing with coronavirus – using sequence information to track that.

FLG: Have people compared tumours within transmissible cancers with human cancers, and are there any similarities? And what are the main differences? Because I’m actually surprised how susceptible Tasmanian devils are to these cancers. And then if you look at the other examples, like there is one in clams, they’re just completely different species. So, I’m interested in these tumours and are they in any way similar to each other, both between the transmissible cancers but also with human tumours as well.

Paul: Yeah, so that’s a really interesting set of questions. So as far as similarities among the different transmissible cancers, you’re right. So, you mentioned there are a couple transmissible cancers known from mussels and clams. There’s one known in dogs that has been around for thousands of years, probably about as long as dogs have been domesticated. And then these two in Tasmanian devils. There hasn’t been really strong evidence for similarities among those that would lead to some common feature that made them transmissible; they each seem to have unique features. On the other hand, transmissible cancers in devils and in those other species do have some similarities to other sorts of cancer, so human cancer, for instance. One of the hallmarks of all of those is an increase in mutation rate, so the genetic mutation rate. So that’s what you would see in a human cancer is large-scale genetic changes within the cell population of a tumour and you see that same sort of thing in DFTD. So large-scale genetic changes among the different strains of DFTD that have developed just within the past couple decades.

FLG: Is anyone using these more advanced technologies, like single cell and spatial technologies, to delve further into these tumours?

Paul: You know, that’s a good question, probably someone somewhere is doing single cell sequencing to understand some of the dynamics of these. That certainly is happening in human cancer research. And I guess I should mention, getting back to your question of how does evolution relate to human health? A cancerous tumour is an evolving population of cells. And so, thinking about the evolution within that group of cells, even within a human cancer, is a really valuable approach to assessing treatment options, that sort of thing.

FLG: How is your research in Tasmanian devils being applied within conservation efforts?

Paul: So, there are some ongoing issues in devil conservation. So, one aspect is that when the disease first appeared, the assumption or the prediction was that it would drive populations extinct. And so, one thing that was done was a set of captive devil populations were established, with the idea that if natural populations went extinct, we could reintroduce individuals from those captive populations back into the wild and restore the species. That hasn’t really happened. So those natural populations have not gone extinct, partly because they’re evolving in response to the disease. But now the question is, what do we do with all of these captive individuals? And one suggestion is to continue to reintroduce them back into the wild as a way of supplementing natural populations. But one issue that has come up from our research is that because the natural populations are evolving in response to the disease, the captive populations have not been exposed to the disease. So, if you reintroduce those susceptible individuals from the captive populations back into the wild, that can actually have a very negative effect in terms of the dynamics of the disease. And it can actually be worse than doing nothing depending on how it affects the spread of the disease. So that’s one direct conservation question that we could address with the sorts of data that we’re gathering.

FLG: If you look at the conservation field as a whole, what are some of the challenges that remain?

Paul: Well, obviously, the field of conservation in general faces a lot of very serious challenges. Habitat and environmental change and direct impact on wild populations continues. I think the genetics and genomics tools that we’ve been talking about are one aspect of that. But as I said, before thinking about some of the science fiction kinds of things, we can’t think that genetics and genomics are going to be a magic bullet solution that will solve those conservation problems. They can help provide a lot of valuable information, but they need to be used along with other sorts of conservation approaches.

FLG: What are some of these other conservation approaches?

Paul: Well, I would say in terms of conservation, the main things continue to be protection of habitat that will allow natural species to persist. And controls on direct impacts on population. So, for instance, harvest or hunting or poaching, managing those things so that they allow wild populations to persist. Those continue to be the main features. We can use genetics and genomics to target those, to tailor those and to better understand the impacts of different management strategies, that sort of thing.

FLG: What do you think the future of conservation will look like?

Paul: Well, I think it’s pretty clear that just on a technological level, in terms of genetics and genomics, our tools will continue to advance. Our ability to gather massive amounts of genetic data, and in particular, gather genetic data without even disturbing the individuals or the species that we’re talking about. Those sorts of things will continue to advance. So increasingly, we will be not limited by genetic information. We’ll have whatever genetic information is out there. We’ll be able to gather it in an increasingly inexpensive way. So, the goal is that any information that we might want from genetics will be available. And it’s up to those other sorts of conservation strategies to really play a role but be informed by the genetic information.

FLG: Thank you so much for joining me today, Paul, it’s been really interesting and transmissible cancers are really fascinating. Conservation research is going to continue to be so important and very prominent in society. So, thank you very much.

Paul: Great, thanks. It’s nice to be with you.

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