How researchers have pinpointed the origin of ‘warm-blooded’ mammals

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week, working out when ‘warm bloodedness’ evolved.

Host: Nick Petrić Howe

And the ultra-efficient enzyme that pulls carbon dioxide out of the air. I’m Nick Petrić Howe.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Benjamin Thompson

First up, reporter Adam Levy is investigating a hot topic in the evolution of animals.

Interviewer: Adam Levy

One of the first things we learn about all the different animals when we’re kids is that some of them are warm-blooded and some are cold-blooded. Cold-blooded animals get their heat from the environment, whereas warm-blooded regulate their own temperature. To use their proper terms, warm-blooded animals are known as endotherms, and cold-blooded creatures are called ectotherms. Being warm-blooded takes a lot of energy, which means having to eat a lot more. But it also opens up new opportunities. For example, species are able to stay more active at night, as well as conquer colder habitats. So, this presents a truly fundamental difference between different animals, and warm bloodedness was a major innovation of evolution. But scientists are still grappling with a pretty key question about the history of warm bloodedness.

Interviewee: Romain David

You have warm bloodedness in mammals and in birds, and the question was how did this group evolve.

Interviewer: Adam Levy

This is Romain David of the Natural History Museum in London. In a study out this week, Romain and colleagues have tried to pin down when this change happened in the mammal lineage, using a surprising line of evidence. I caught up with him and asked why it’s so hard to work out when the first warm-blooded animals arrived.

Interviewee: Romain David

It’s hard because in extant organisms you know if one is warm-blooded or cold-blooded by directly measuring its body temperature, its metabolism. You cannot do that on fossil specimens, so you have to choose indirect means to assess these things. And the problem is that there are various ways of assessing metabolism and body temperature of organisms, and often you have conflicting results.

Interviewer: Adam Levy

Now, you and your collaborators wanted to look at something which, to many people, might seem completely unrelated to whether a creature is warm- or cold-blooded.

Interviewee: Romain David

Exactly.

Interviewer: Adam Levy

You were actually looking at the shape of the inner ear. Now, can you explain how this could be connected to the temperature of an organism.

Interviewee: Romain David

I need to explain that the inner ear is very important for major functions of the body, like stabilisation of gaze, navigation, motor coordination, balance. Now, you have to understand that in the inner ear, you have a fluid which is called the endolymph and, as most fluids, its viscosity is affected by temperature. It's a bit like honey. If you warm up honey, it will be much more fluid. So, as temperature increases, when you go from cold-blooded to warm-blooded, the organism will need to modify the structure of the inner ear to compensate for this decrease in viscosity linked to temperature. And this is why looking at the morphology of the inner ear, in a way that is linked to biomechanics, allows us to track this body temperature change in the fossil record in the mammalian lineage.

Interviewer: Adam Levy

So, you now have what, at least you hope, is an indirect means of assessing whether an animal, at least in the mammal lineage, is warm-blooded or not. How do you actually then kind of use this to trace how warm bloodedness may have evolved?

Interviewee: Romain David

Because we know that the endolymph of mammals, in terms of composition, is not very different from the endolymph of fishes, we assume that the composition of the endolymph did not change during time. So, what we need to look for is the morphofunctional changes of these fossils that leads to functions that are compatible with high body temperature.

Interviewer: Adam Levy

When you actually look at this and kind of trace the history of the inner ear canal back to try and get a sense of when organisms started raising their body temperatures, well, what do you actually find?

Interviewee: Romain David

About 233 million years ago, we find a big jump in body temperature of about 5-9 °C, which was a bit unexpected compared to what has been proposed before because the general idea was that first to transition from cold bloodedness to warm bloodedness was something that has been gradual, which is absolutely not what we find. We find that this has been an abrupt shift.

Interviewer: Adam Levy

So, in this study, you suggest that warm bloodedness came about actually, really relatively quickly. Do you have any idea why that might have been the case?

Interviewee: Romain David

So, for endothermy, for warm bloodedness to be complete, you need to be able to produce your own heat, and you need to be able to retain it, to keep it inside your body. I mean, you have several ways of explaining this shift, but it's likely, what the thing that we think is the correct interpretation, is that the presence of these two characteristics marks this shift.

Interviewer: Adam Levy

How surprised were you, looking at the data that you got out, to see such a sudden shift?

Interviewee: Romain David

Very surprised, and because we tried several times to see if it was holding. This was clearly marked by the data.

Interviewer: Adam Levy

Now, do you think other researchers will necessarily agree, especially considering that other studies seem to show other answers?

Interviewee: Romain David

I don't think they have to agree. I think that will certainly spark debate and further research. I don't think I'm wrong by saying it’s the study with the largest sample on fossil synapsids yet. I mean, scientists have to doubt. I will be more than happy if this sparked more research in that area.

Host: Benjamin Thompson

That was Romain David from the Natural History Museum here in the UK. To read more about this story, look out for a link to the paper in the show notes.

Host: Nick Petrić Howe

Coming up, we'll be hearing about an enzyme that's really good at pulling CO2 out of the air. Right now, though, it's time for the Research Highlights with Dan Fox.

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Dan Fox

Most surgical wounds are sewn closed with sutures. While adhesive dressings can be used, so far, most have been either too weak to keep wounds sealed, or too strong to be painlessly peeled off. But now, researchers have developed an adhesive for closing wounds that’s stronger than a commonly used commercial product and lifts off when submerged in water. To create it, the team mixed boric acid with a polymer often found in school glue. The polymer’s alcohol units bond with boron atoms in the acid, creating an adhesive that dries into a strong film. But when water is present, the boron atoms switch to bonding with water molecules instead, and the adhesive can be removed. The researchers showed that the adhesive film could firmly hold furry mouse skin together but could be peeled off easily after being submerged in water. They hope that the films can close human wounds too, even on a child’s delicate skin or on unshaven skin. Keep your eyes glued to that research in The Proceedings of the National Academy of Sciences.

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Dan Fox

Industrial whaling in the twentieth century drove the southern fin whale to near-extinction. But now, after a decades-long absence, huge pods of these animals have returned to their historical feeding grounds in Antarctica. By the time fin-whale catches were banned in 1976, researchers rarely sighted them around the Antarctic Peninsula, a former hotspot. But in 2018, researchers scanned the sea for fin whales, both from their research vessel and by helicopter. Using models to extrapolate from their observations, they estimated that almost 8,000 fin whales were swimming in one area of Antarctic water — a higher density than has been seen at other well-known fin-whale habitats. The authors also witnessed ‘feeding frenzies’ of up to 150 animals devouring krill together. The authors say that the fin whales’ nutrient-rich faeces could help to reinvigorate the surrounding marine ecosystem, which was damaged by whaling. Head over to Scientific Reports to observe that research.

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Interviewer: Nick Petrić Howe

There’s too much carbon dioxide in the air, and it is becoming clear that, in order to stem the worst impacts of climate change, we need to find a way to pull it out, with things like carbon capture and storage, or by stopping it being released in first place, by using things like hydrogen as a fuel source rather than fossil fuels. I probably don’t have to tell you that these are both considerable challenges, but what if I said that there is an enzyme that potentially has the ability to make things easier – both capturing carbon dioxide and making hydrogen easier to store for fuel. It is the catchily named hydrogen-dependent CO₂ reductase (HDCR). It converts hydrogen and carbon dioxide to formic acid, which can be used as a fuel, and it does this by taking an electron from the hydrogen to reduce the carbon dioxide. And this conversion is done really, really efficiently. But nobody has been quite sure how. Well, now, in a new paper in Nature, a team of researchers are putting forward an explanation, and it has come from a detailed look at the structure of HDCR. I called up one of the authors, Jan Schuller, to find out more, and started by asking why he became interested in this enzyme.

Interviewee: Jan Schuller

So, I got to know this enzyme in a conference, and I heard Professor Müller talking about this enzyme, and he's actually the discoverer of this enzyme, and it was really fascinating. And I couldn't get my head around why we don't understand how it actually works and why it's so efficient, and this is what started the project. So, in the in the break of the conference, I actually walked up to Professor Müller and asked him, ‘Hey, do we want to cooperate on this?’

Interviewer: Nick Petrić Howe

So, just tell me a little bit about this enzyme. What's so special about this enzyme?

Interviewee: Jan Schuller

It’s the only enzyme which is capable of directly reducing CO₂ using molecular hydrogen, and it does it particularly well. So, if you compare the catalytic rates, they are 10,000 times more efficient than non-chemical catalysts. They are fully reversible and at room temperature. This makes this a very special enzyme. It's useful for biotechnological applications, such as hydrogen storage. And we, as a structural biologists lab, we want to understand how it actually does its job so well.

Interviewer: Nick Petrić Howe

And so, how did you go about trying to figure out how it does this job so well?

Interviewee: Jan Schuller

So, we managed to purify the HDCR from its native organism, and froze it down for electron microscopy techniques. So, we imaged with an electron microscope and collected thousands of images of the same protein in different orientations, just frozen on a thin layer of ice. And using computational methods, we could then reconstruct its 3D structure. And it was cool because we saw actually they were filaments, short filaments, which had the enzymes sticking out like little mushrooms out of the centre of the filament. And when we built the model, we saw, ‘Oh, wow, that's really cool.’ We actually see a chain of iron-sulfur clusters in the centre of the filament. And this forms an electron wire, so connecting the different enzymatic activities. And then we thought, ‘Okay, if we elongate this filament now in our mind, what do we actually get?’ Yeah, we get an enzymatic decorated electron wire, and this is really cool.

Interviewer: Nick Petrić Howe

Oh, that's really interesting. So, they've got sort of basically little wires where electrons can be shuttled along. What could that mean for the sort of enzymatic activity?

Interviewee: Jan Schuller

Because this means you spatially and temporally can separate the reactions of the enzyme, this means one side of the electron could oxidise the hydrogen while the other side of the electron could reduce the CO₂. So, you could separate directions of a certain distance. And the other very interesting phenomena about electron nanowires is that they actually have been described to store electrons for certain time. So, if we would extend the idea a little bit, we don't only have an enzymatic decorated nanowire, we also have, well, it's not really a bio battery, but something that could, at least for a certain degree, make use of an excess of hydrogen. This could be useful for the bacteria if it, for example, meets a hydrogen bubble where this charges up all of these filaments, and then keeps the electron for a certain time stored until it meets a bubble of CO₂.

Interviewer: Nick Petrić Howe

Does this give you a clue or any idea as to quite why this enzyme is as efficient as it is?

Interviewee: Jan Schuller

Yeah, first of all, it links a lot of different active sites. So, two hydrogenases are linked to one formate dehydrogenase. So, this means basically we can oxidise twice as much hydrogen. And on the other hand, it probably also stabilises the entire reaction. So, the enzyme is really strongly connected. So, other formate dehydrogenases, they don't do this. They cannot take the electrons directly from hydrogen. They instead need a soluble electron carrier like ferredoxin or NADPH or something like that. So, I think taking the direct route is probably faster, instead of taking like the carrier route.

Interviewer: Nick Petrić Howe

So, as I understand it as well, you didn't only look at these enzymes on their own, you also looked at them within the organism itself. When you did this, what were you able to see?

Interviewee: Jan Schuller

Yeah, so we also actually then wondered if indeed these nanowires exists in these bacteria, and we saw big surprise. So, we did not detect filaments. No, we actually detected bundles of filaments. And these bundles of filaments, they formed superstructures. I called them ‘portals’ because they actually looked like something from Stargate, that they go in a different dimension through them, and they're huge. So, it’s the size of like 200 nanometres, and basically you could even fit the ribosomes in these portals. And, just imagine, right, the huge amounts of this enzyme, which forms these rings, and they're always located at the tip of the cell. And these huge barrels, they have hundreds and thousands of enzymatic subunits, and every one of these enzymatic subunits has like 10-15 electron clusters. So, what is this? We don't know. But I find it very, very interesting that it actually sits in the biggest bioenergetic compartment of the cell. It would be imaginable that there is a link between the electron transfer and CO2 fixation in the membrane potentially. But this we don't know yet. This is where we need to do further experiment.

Interviewer: Nick Petrić Howe

I guess I'm wondering when you first were able to image this? Was it what you were expecting or was it quite surprising? Were you like, ‘Oh, I wasn't expecting it to look like that at all’?

Interviewee: Jan Schuller

We definitely did not expect it. So, we were very happy when we saw something which looked a little bit like hairs or fibres. And we thought, ‘Yeah, maybe we found them.’ Actually, false filament and then might be close to the membrane. And then we saw the 3D reconstruction. We have never seen something like that in the bacterial cell. And actually, we had a look at a lot of bacterial cells before.

Interviewer: Nick Petrić Howe

I guess now, by understanding this – you've mentioned sort of biotech applications and things in your paper – could this now be used to make different things in the real world?

Interviewee: Jan Schuller

This is something that, of course, can be tried. And acetogens, are actually a prime organism for biotech. So, there are big companies working on fermentation facilities for acetogens. And, of course, our structure could be of interest for them. We could, for example, change the activity of the hydrogenase, and that would be cool because this means we could use not only pure CO₂, but CO₂ which is also a little bit contaminated with carbon monoxide to actually fix the CO₂. Also, one could envision linking other activities to it, like reductive enzymes. So, one could, in theory, cable a lot of enzymatic reaction to this nanowire. And this nanowire arrangement would make them, yeah, we do hope makes them more efficient.

Interviewer: Nick Petrić Howe

That was Jan Schuller from Philipps-University in Germany. To find out more about this work and to check out the structure for yourself, be sure to look out for a link to the paper in the show notes.

Host: Benjamin Thompson

Finally on the show, it’s time for the Briefing chat, where we discuss a couple of articles that have been featured in the Nature Briefing. Nick, why don’t you go first this week. What have you got for us?

Host: Nick Petrić Howe

Well, this week, I’ve been looking into some reports that have come from the Intergovernmental Science-Policy Panel on Biodiversity and Ecosystem Services, which I’ll call IPBES for short. But I was reading about these reports in Nature – we’ve got two articles there and I’ll focus on one of them first – and this is where scientists have tried to work out how many different ways there are to value nature, and by that, I mean the stuff that goes on outside, not the journal we work for.

Host: Benjamin Thompson

Okay, well, I guess, so many products that are found in nature are really, really important for health, for the economy, for people's livelihoods and so on, right?

Host: Nick Petrić Howe

Yeah, that's right. There's a lot of different ways to value nature, and it could be more sort of spiritual things or it could be more economic things, like pollination and that sort of thing. And this new report has found that there are actually 50 different ways that you can value nature. But the thing that they’ve found as well is, while there are many, many different ways to value nature, research only focuses on a few different ones.

Host: Benjamin Thompson

Right, so only a subset of the total ways that nature can be valued. What are some of the big ones that are being looked at then, and what are some of the ones that are being missed out?

Host: Nick Petrić Howe

So, the key one that is often focused on is this sort of economic valuation of nature. I talked about pollination earlier. That's a very easy example. Pollination happens, that increases the yields of crops, and therefore you have more crops and you have more money. And researchers really focused on this sort of way because it's quite easy for policymakers to understand. But by focusing on this sort of economic valuation, this report has found that it can be harmful to people and the environment. So, I'll give you an example. When there are proposals for hydroelectric dams, the needs of the affected communities are often seen as secondary to those who would benefit from the dam – those who are getting the electricity. So, despite the fact these people have to move because maybe the place where they live has been flooded, the people who are getting the value, the monetary value of the electricity and that sort of thing, they get valued a bit more. And that has all sorts of consequences for those communities and for nature as well.

Host: Benjamin Thompson

I guess policymakers would argue that there's always going to be a balance between these 50 different things that are important. Is it possible to envisage a situation when all of them are considered or included when making policy or when making decisions?

Host: Nick Petrić Howe

It's certainly a considerable challenge, and what this report does is just try to emphasise that there are these other ways to value nature and, if we don't value nature in all these different ways, it can lead to decline in the services that nature provides and also damage to nature and communities, especially Indigenous and low-income communities. So, the report really says that one of the ways that we can help tackle this is by including people from the places that are actually affected, from these places of high biological diversity getting their viewpoints across so we can better value nature in these more diverse ways. And one way that we do value nature, and this is the second article that I wanted to talk about, is we rely on many plants and animals for food, energy and medicines, all sorts of things, and in many ways, we actually overexploit that as well.

Host: Benjamin Thompson

Yes, I mean, I think the world is in the midst of a biodiversity crisis, of course, with species going extinct at an alarming rate. And I'm sure that a great many of those species are super important to ecosystems and could be beneficial to humanity as well.

Host: Nick Petrić Howe

Yes, they certainly are. And I will say, what this is, is about wildlife. These are the wild species that we rely on. And this report calculates that there are 50,000 plants, animals, fungi and living organisms that we rely on as a species and, in many cases, actually overexploit. And that overexploitation is a big threat, but this report from IPBES also points out that there are some species that we seem to be using in a sustainable way, and maybe we can focus on how that is being achieved in order to stop this sort of overexploitation of species.

Host: Benjamin Thompson

And so, does the report give any insights or suggestions into how species could be used in a sustainable way then?

Host: Nick Petrić Howe

Yeah, so what they've done is they've looked at a subset of these 50,000 species that humans rely on, they've looked at 10,000, and found that around a third of these have stable populations. And in the report, they interpret this as those species being used sustainably. And from that, they're able to look at those and then work out what's been done there that we can replicate, and they talk about things like securing land rights for Indigenous people, raising awareness about these species, and doing more scientific research to work out what's been done with these populations that makes it more sustainable. But at the same time, people have been quite critical of this report because they've pointed out that just because these populations are stable doesn't necessarily mean that they're being used in a sustainable way.

Host: Benjamin Thompson

And so, what happens next then, Nick? So, this body of work is now out there and is clearly being discussed. What are the next steps?

Host: Nick Petrić Howe

Well, some people interviewed in the article say that this report couldn't have come at a better time because countries are currently negotiating the next big global biodiversity agreement, and that will set the conservation agenda up until 2030. So, later this year, there will be the Conference of the Parties to the UN Convention on Biological Diversity in Canada, and that will be in December. So, having this information now will be really useful to sort of set the agenda there. But researchers have pointed out there are also some gaps in data within this, and so they would like to see them sort of closed before then. But the team behind the reports say that we need to use the data we have. We need to push forward and show what is going on with biodiversity to make recommendations.

Host: Benjamin Thompson

Well, I'm sure that's the story we'll be keeping an eye on. But let's move on to mine this week. And also, it is about nature – the stuff outside – and this is a story that I read about in Science and it's based on a paper in Current Biology, and it's all about woodpeckers.

Host: Nick Petrić Howe

Okay, I do love nature – the stuff that goes on outside. So, what is this saying about woodpeckers that we didn't know before?

Host: Benjamin Thompson

Well, I mean, I think woodpeckers are pretty cool, right? I mean, I was on holiday last week at my in-laws’ house, and they live in the forest and they have a bird feeder outside the window, and a woodpecker does come sometimes, and it's a really, really cool thing, right? It's a Great Spotted Woodpecker, I think. And what's cool about this species, and about other woodpeckers too, is about how quickly they can peck at wood. And so, for the Great Spotted Woodpecker, for example, it's potentially up to 20 times a second it can bang its beak against the tree, which is pretty amazing. But a big question in biology is how are woodpeckers not giving themselves a massive headache or even a concussion when they are smashing their heads against the tree that rapidly. And I'll say what's commonly been assumed, is that they have kind of a built-in shock absorber, right? So, woodpeckers have this spongy bone in the front of their heads, and researchers kind of thought that that was like an airbag, okay, that was protecting their skulls as they were rat-a-tat-tatting against trees. And this had been used to develop things like crash helmets. So, it was written down everywhere, right, so a very widely accepted belief, right, presented as facts. But there was a problem with that, Nick, and it is that it looks like it isn't true at all.

Host: Nick Petrić Howe

I was waiting for the other shoe to drop when you were explaining that. So, if it's not the shock absorbers, what is going on here?

Host: Benjamin Thompson

So, what's happened here then, Nick, is researchers recorded a bunch of high-speed videos, which are absolutely amazing, of 6 woodpeckers from 3 species, including the Great Spotted Woodpecker that I think I saw from the window the other day, and they tracked points on their heads and beaks as they were pecking to work out what was going on. And it turns out, if they're not using shock absorbers, what are they using? The answer is nothing. So, in these videos, when they bang their beaks into the tree, their head doesn't slow down any more than the beak at the point of impact, so it's all hitting at the same speed. So, if you think of it like a hammer, it just keeps banging away, rather than the head slowing down more gradually, if it had sort of an airbag situation going on. And what the team also showed is that, if there was this shock absorbing thing going on in the woodpeckers’ heads, they wouldn't be able to input as much force when they pecked, so they would have to peck a lot harder to get the same sort of drive into the wood, which would negate the having the shock absorbing there in the first place.

Host: Nick Petrić Howe

But then surely they are hurting themselves. Are they not getting damage? Like if they're not doing this?

Host: Benjamin Thompson

That's a very, very good question. And they did some more modelling here as well, from what I understand, and I think it comes down to their brain. So, Nick, humans, as we know, have very big, quite heavy brains. So, if I started smacking my head into a tree, there would be a lot of banging around going on inside my head. I would get a concussion. That would be that, right? But it turns out that the woodpeckers have got a lot smaller, lighter brains, and so the forces on them aren't nearly as bad when they start pecking. And what the researchers worked out was for them to get a similar sort of injuries that that I would experience, they would have to peck twice as fast or hit something very, very hard, like, say, a metal rod, for example. And so, they don't suffer the same injuries that we would. And it's kind of, I guess, rewriting the textbooks, I guess, from what people assumed.

Host: Nick Petrić Howe

Okay, so I guess, have we just been sort of slightly anthropomorphising them in a way and being like, well, if I did that, I will be really injured. But actually, it's just not the case.

Host: Benjamin Thompson

It seems like that has been what's going on to an extent, Nick, yeah, and then there were other theories, too, right. Now, woodpeckers have very, very long tongues, and it was thought that these would kind of wrap around the backs of their brains a little bit and maybe that was like a seatbelt to protect them. But again, that appears to not be the case. But it's interesting that some of what doesn't appear to be true has actually influenced, as I say, like American football helmets and so forth. So, a whole branch of science has come off this thing that doesn't appear to be there.

Host: Nick Petrić Howe

Is this the end of this story? Is this now just how we think about woodpeckers? Or what's the sort of future of this work?

Host: Benjamin Thompson

Well, there are some researchers, it seems, that aren't quite ready to give up on this kind of shock absorption idea just yet. But I think what this work does show is that woodpeckers really are amazingly sort of adapted to their lifestyle, and their lifestyle is smacking their heads, with incredible force, repeatedly against a tree. And I think, given the way the world has been in the last few years, some of us might feel like that's what we've been doing as well.

Host: Nick Petrić Howe

That is super interesting. Thanks so much, Ben. I think that's all we've got time for on the Briefing chat this week. But listeners, for more on those stories and for where you can go to sign up to the Nature Briefing, check out the links in the show notes.

Host: Benjamin Thompson

And that’s all for this week’s podcast. But as always, you can reach out to us on Twitter – we’re @NaturePodcast. Or you can send us an email to podcast@nature.com. I’m Benjamin Thompson.

Host: Nick Petrić Howe

And I’m Nick Petrić Howe. Thanks for listening.