From dodos to Neanderthals, it's boom times in ancient DNA research : Short Wave Research into very, very old DNA has made huge leaps forward over the last two decades. That has allowed scientists like Beth Shapiro to push the frontier further and further.

"For a long time, we thought, you know, maybe the limit is going to be around 100,000 years [old]. Or, maybe the limit is going to be around 300,000 years," says Shapiro, Professor of Ecology & Evolutionary Biology at UC Santa Cruz. "Well, now we've been working with a horse fossil in Alaska that's about 800,000 years old."

Beth's career has spanned the heyday of ancient DNA research, beginning in the late 1990s when rapid genetic sequencing technology was in its early days. She talked with Short Wave co-host Aaron Scott about the expanding range of scientific puzzles the young field is tackling — from new insights into our Neanderthal inheritance to deep questions about ecology and evolution.

It's boom times in ancient DNA research

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You're listening to SHORT WAVE from NPR.


For Beth Shapiro, it all began with a dead bird, a very special dead bird.

BETH SHAPIRO: Our ancient DNA lab was at the Oxford University Museum of Natural History. And as I would walk through the museum back to our lab every day, I would pass by what's arguably that museum's most famous specimen, this dodo.

SCOTT: It was one of the few dodos that was brought back to Europe, before Europeans famously wiped the birds from the face of the Earth. And to Beth's knowledge, it was the only one with any soft tissue remaining. To the average dodo observer, that might be a little more than a fun fact. But to a young scientist like Beth, interested in what was then the fledgling field of paleogenomics, it was a potential treasure trove of ancient DNA.

SHAPIRO: Nobody knew much about the dodo at the time, including what kind of bird it was most closely related to. So I asked the curators if I could please have a tiny piece of that dodo, and they said, absolutely not.


SHAPIRO: Not until you prove to us that you're actually good at this. And so I did try to extract DNA from some less precious extinct birds and was successful and eventually got permission to get DNA from that dodo.

SCOTT: Her first scientific publication concluded for the very first time that the dodo was a type of pigeon.

SHAPIRO: I'm not sure if people are very excited about that or not, but I was. It's maybe a little bit disappointing. But it's very closely related. It's most closely related to a pigeon called the Nicobar pigeon, which is this small, very strong flying, absolutely gorgeous bird, you know, really different in physique and appearance and behavior from what we know about dodos. But, you know, the magic of DNA.

SCOTT: This was 2002. We were already three movies into the "Jurassic Park" franchise. But while the idea of accessing the DNA of long-dead creatures had been soaring through popular imagination for years, the actual science, it had barely left the nest.

SHAPIRO: You know, everybody was racing to try to get the oldest and coolest DNA out of the oldest and coolest samples everywhere in the world. And the field had really been through a bit of a comeuppance, I'd say. You know, most people had realized by that point that most of the really old DNA was not real. It was just contaminants introduced by touching the sample or processing it in a lab that wasn't sufficiently clean.

SCOTT: With the limited technology of the day, Beth was only able to sequence small fragments of mitochondrial DNA from the dodo. But she kept at it, eventually opening up her own lab at the University of California, Santa Cruz, winning a MacArthur Prize and writing books like "How To Clone A Mammoth." Meanwhile, the technology has been catching up.

SHAPIRO: It wasn't until 2016 that we were able to use the new type of sequencing, next-generation sequencing, and get a whole mitochondrial genome from that sample and confirm the results that we had, that I had gotten many years before using just those small fragments of mitochondrial DNA. And now, of course, we have a complete genome sequence, a nuclear genome sequence from the dodo, and we haven't published that yet.

SCOTT: Today on the show, we talk about just how far the field of ancient DNA has come in a little more than 20 years and how it can help us solve some really big mysteries, like why did certain woolly mammoths go extinct? Or who were ancient Homo sapiens sleeping with - or what? Oh, yes, paleo-gossip, people. I'm Aaron Scott, and you're listening to SHORT WAVE, the daily science podcast from NPR.


SCOTT: Beth, would you tell us just a little bit about why ancient DNA is so difficult to study? I mean, what happens to DNA over many centuries?

SHAPIRO: As soon as an organism dies, the DNA within its cells starts to break down into smaller and smaller and smaller fragments until, eventually, there's nothing left. This process of breaking down the DNA is by things like UV radiation from the sun, freezing and thawing. Water molecules will expand and physically break the DNA. And then also by the action of microbes, fungi, bacteria, whose job it is to get into decaying material and chew it up, recycling all of this material into the next generations. We know that this process is slower in some environments - really cold places, for example.

We also now know that you can get fragments of DNA directly from dirt and sediments, that you can go into a cave, for example, and collect dirt from the floor, or you can go on a boat out into the middle of a frozen lake and stick a big core down into the bottom of that lake and suck out some of the mud from the base of the lake. And that mud will contain a stratigraphy, a history of all of the dirt that was settled into the bottom of that lake over time, including the plants and animals of that community.

SCOTT: Wow. I didn't realize. So the eDNA can kind of be used through centuries and core samples. I had no idea that you could map kind of whole ecologies over time.

SHAPIRO: Yeah. One of - the question that I was involved with - there's this really neat study. We were interested in - so the last two places that mammoths lived were Wrangel Island, off the northeastern coast of Siberia, where they survived until around 3,200 years ago, and Saint Paul Island in Alaska. We weren't sure exactly when mammoths went extinct there, but it was sometime around 6 - 5-, 6-, 7,000 years ago. And there's one source of fresh water on Saint Paul Island, and it's a volcanic caldera, so it captures rainwater. There were a bunch of people from different universities who were interested in different aspects of paleoecology that were part of this team, went out onto the lake in the winter and drilled a big core. We captured pollen grains and fungal spores, and we looked at things like cladocerans, little animals that live in the water. And the species of the animals that are there can tell you about whether the water was salty or turbid or shallow.

And so we collected all of this information down the core, and we saw that mammoth DNA disappeared around 5,700 years ago. And we saw that there was really no change in the plant community. So it wasn't that, all of a sudden, the mammoths living there didn't have anything to eat. But we did see huge changes in the rate of sedimentation and in the communities of things like diatoms and cladocerans that were telling us that the lake was getting saltier and getting more turbid and more shallow. And so this told us that the reason that mammoths went extinct on Saint Paul Island around 5,700 years ago was probably because of a massive drought. So we solved the paleontological mystery using environmental DNA and other paleoecological indicators. Pretty cool project.

SCOTT: And I'm curious - is there an expiration date for DNA, then, in this kind of work? I mean, is it possible to find the DNA of dinosaurs, a la "Jurassic Park," in a mosquito preserved in amber somewhere? Or is there kind of a certain length at which the DNA has degraded so much it's no longer useful?

SHAPIRO: There's not an easy answer to that. For a long time, we thought, you know, maybe the limit is going to be around 100,000 years, or maybe the limit is going to be around 300,000 years. Well, now we know that we can get DNA from fossils that are - we've been working with a horse fossil in Alaska that's about 800,000 years old, and we have a whole genome from that. And recently, Eske Willerslev's group got environmental DNA that may be as old as the early Pleistocene or even the late Pliocene. So it could be around 3 million years old. I mean, you asked about dinosaurs. Dinosaurs went extinct more than 65 million years ago, assuming you're talking about non-avian dinosaurs, right? Because we're science nerds.

SCOTT: Yeah.

SHAPIRO: So we have to make that distinction, right? (Laughter).

SCOTT: Of course, of course.

SHAPIRO: We're never going to get DNA from something that's that old. There's just no real preservation environment that I think will allow that. But, you know, I would have said never to 3-million-year-old DNA before, you know, several months ago. So who knows?

SCOTT: Can you tell us a little bit about the big technological shifts that have led to this huge leap in decoding ancient DNA? I mean, take us through kind of the story of how the tech has evolved during the course of your lifetime and your research.

SHAPIRO: As a field, ancient DNA is really driven by the technologies that are available to us. When I first started working in ancient DNA, we really could only use Sanger sequencing. This was a type of sequencing of DNA that required DNA fragments that were preserved to be pretty long, pretty much on the order of at least 100 to 120 bases long. And this is because you had to use primers that are, like, very specific fishing lures. And then when next-generation sequencing technology emerged, this sort of new generation of approaches to targeting sequence data that doesn't require these primers, where you can just sequence everything that's in these samples, that really changed the field a lot. Suddenly, we could push into older samples and poorer environments for preservation. We could get DNA that was 20 bases, 25 bases, 30 bases long. And we've seen since then that that new technology really is what allowed ancient DNA to take off as a field.

SCOTT: I'd love it if you'd talk a little bit about just kind of the range of scientific questions that you're now using paleogenomics to understand. What are the things you're most excited about?

SHAPIRO: What keeps drawing me back to ancient DNA is that it's kind of the way that we can be a modern-day explorer. And I think a lot of people are motivated with ancient DNA to learn more about us. You know, we're - as people, we're very selfish. We're mostly interested in ourselves and in our own evolutionary history. And ancient DNA really makes it possible for us to dig into what it is to be human in a way that we couldn't do before. We now have many Neanderthal and Denisovan genomes, and all of a sudden, the length of evolutionary distance that lead just to people is much shorter. So we can really narrow down what it is that makes us human.

SCOTT: Can you tell us a little bit about how this ancient DNA has kind of turned on its head our understanding of what the relationship of Homo sapiens and Neanderthals were?

SHAPIRO: One of the first discoveries that the teams that were working on Neanderthals made was that there was a very strange pattern in the early data that seemed to suggest that people of European descent shared more ancestry with Neanderthals than people of sub-Saharan African descent. And the only way that this could be explained is if after the small group of people that went on to colonize Europe and then Asia had actually interbred with Neanderthals after leaving Africa. Now it's kind of common knowledge. Most people have somewhere between 2 and 3% - or something like this - Neanderthal ancestry.

SCOTT: (Laughter).

SHAPIRO: What's less well known is that it's a different 2 to 3%, and if we were to gather up all of the bits of Neanderthal DNA that's scattered in the genomes of people who are alive today, we could put together about 93% of the Neanderthal genome.


SHAPIRO: And this tells us two things - first, that that other 7% of the genome, that's the important part. That's where we need to start looking if we really want to know what makes humans human rather than similar to our archaic cousins. And second, I think it also makes us question what it means to be extinct. Are Neanderthals actually extinct if 93% of their genome still persists among us? I mean, yes, I would say yes. But it's an interesting philosophical question, nonetheless.


SHAPIRO: We've learned that sometimes when - I mean, some of the Neanderthal heritage has actually been really adaptive, really good for human populations that got it. You know, one of the first to be identified was MHC alleles, alleles that are involved with resistance to disease. You can imagine that if you move into part of the world where Neanderthals have been living, they have their own circulating diseases, and they have their own evolved defenses against those diseases. And so if you are suddenly exposed to those diseases, maybe it benefits you to have the Neanderthal version of the immune genes that help keep you alive. So mixing with these archaic cousins was beneficial to some of these human populations, as well as, you know, pretty much - not necessarily being detrimental, which is what it means that 93% of their genomes still exist, but that other 7% - some parts of that other 7%, if a human were born with it, they could not survive as a human, and that part got kicked out of our genome. That is where we want to look.


SCOTT: So the science of ancient DNA is rewriting the past, but also maybe the future. We're going to continue this conversation with Beth Shapiro tomorrow and get into the question that everyone has asked her since that very first paper on the dodo - can we bring these animals back from extinction?


SCOTT: This episode was produced by Thomas Lu, edited by Gabriel Spitzer and fact-checked by Anil Oza. Our audio engineer was Jay Czys. Rebecca Ramirez is our managing producer. Brendan Crump is our podcast coordinator. Beth Donovan is the senior director of programming. And Anya Grundmann is the senior vice president of programming. I'm Aaron Scott. Thanks, as always, for listening to SHORT WAVE from NPR.


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