A 3D reconstruction of the woolly mammoth genome might help revive the extinct species

Scientists have recreated the three-dimensional structure of the woolly mammoth’s genetic blueprint.

The accomplishment, described Thursday in the journal Cell, marks what is believed to be the first time scientists have been able to produce a multidimensional version of the genome of a complex extinct species.

The advance should provide important new insights into the biology of a creature that has long sparked fascination. In addition, the work could aid efforts to breed a living version of the animal, the researchers and others said.

“It’s exciting,” says Erez Lieberman Aiden, a professor of of molecular and human genetics and director of the Center for Genome Architecture at the Baylor College of Medicine in Houston. “We think it’s going to be very valuable.”

For years, scientists have been able to peer back in time by analyzing fragments of ancient DNA recovered from bones, fossilized teeth, mummies and even strands of hair.

“In biology, one of the most powerful tools for understanding the history of life on this planet is ancient DNA,” Aiden says. “It’s an incredibly powerful tool for understanding the history of life.”

But there’s only so much scientists could learn from snippets of DNA. So Aiden and his colleagues launched an international effort to try to recreate the three-dimensional structure of the DNA, including the chromosomes, of an extinct creature.

“In so doing, you would be able to see exactly how that chromosome was shaped in a living cell, and you’d be able to both get a deeper understanding of the genomes of ancient and extinct species and how those genomes worked – which genes were on and off in particular tissues,” Aiden says.

Searching for mammoth samples on eBay

The scientists focused on the wooly mammoth, a big, shaggy species of elephant that roamed the tundra thousands of years ago.

“Initially we had embarrassingly bad ideas. I’m a little ashamed to admit it,” Aiden told NPR. “We said, ‘Oh, you know, that looks like a good-looking piece of mammoth on eBay. Let’s try that.’ It’s kind of a little cringe, right, to tell you that. Ebay is a bad place to get your mammoth samples.”

After searching for five years, the team finally found a well-preserved mammoth sample: skin from behind the ear of a 52,000-year-old female that was discovered freeze-dried in Siberia in 2018.

“It was a piece of a mammoth skin that was, you know, wooly. True to the name — it was indeed woolly mammoth skin,” says Olga Dudchenko, an assistant professor at the Baylor Center for Genome Architecture who worked on the research. “And that’s actually not as trivial as it sounds because very often the hair would be lost. So this one was hairy. And that actually is an interesting indicator in and of itself that this is a sample of substantial quality. And that immediately piqued our attention.”

Scientists can look at individual mammoth genes

In fact, the quality of the sample enabled the team to extract DNA and use a technique known as Hi-C to reconstruct the three-dimensional structure of all 28 of the mammoth’s chromosomes — the extinct creature’s entire genome, the researchers reported.

“We were able to assemble the genome of a woolly mammoth just as 25 years ago humans were excited for the first time to assemble our own genomes,” Aiden says. “Now we can do that for animals that were long extinct. That’s obviously a milestone.”

Not only that, the team has been able to peer into the genome to start learning what individual genes did.

“And that’s really exciting to be able to look at an extinct creature and be able to say, ‘Oh, yes. I can see this gene was on. That gene was on. This gene was off. Oh, isn’t that surprising?’” Aiden says. “To be able to do all these specific things in a woolly mammoth is exciting.”

In fact, by comparing the mammoth genome to DNA from modern elephants, the scientists have already discovered clues to what made the woolly mammoth woolly.

“We’ve been internally discussing whether we should start Hair Club for mammoths?” Dudchekno jokes.

Genetic findings could aid efforts to bring back mammoths

But seriously, that insight could help efforts that are already underway to try to bring a version of the mammoth back from extinction — by endowing modern-day Asian elephants with mammoth traits, such as their hairiness, and perhaps even release them to graze the tundra again.

“I do think that this can be helpful for de-extinction,” Aiden says.

Other scientists praised the work.

“I think it’s pretty cool,” says Vincent Lynch, an associate professor of biological sciences at the University at Buffalo who was not involved in the research.

But Lynch isn’t a fan of trying to bring back the mammoth. The unintended consequences of that could be disastrous, he says. And the money for such a project would be much better spent trying to save the elephants that still roam the planet today.

“There’s an huge potential for unintended consequences,” Lynch says. “Just think about all the other invasive species that are in the world. You don’t really know the effect that species is going to have in the environment until it gets there.”

And Karl Flessa, a professor of geosciences at the University of Arizona agrees on the scientific accomplishment and the foolishness of trying to bring back the extinct pachyderm.

“The preservation of genetic architectures from the woolly mammoth is really remarkable,” Flessa says. “But just because you can do it, doesn’t mean that it should be done. A genetically modified Asian elephant is not a wooly mammoth. And releasing such an animal into the wild would be arrogant and irresponsible.”

Others disagree.

"It's exciting to see that 3D architecture can be preserved in ancient samples. This will help move toward a complete de novo assembled mammoth genome, which could reveal features of the genome that might be relevant to mammoth de-extinction,” Eriona Hysolli, who leads a project to create an Asian elephant with mammoth traits at Colossal Laboratories & Biosciences in Dallas, wrote NPR in an email.

Still, Robert Fleischer, a senior scientist for the Center for Conservation Genomics at the Smithsonian’s National Zoo & Conservation Institute in Washington, says that prospect is exciting.

“If I was a 12-year-old in my science class in junior high school I’d probably think this was pretty cool,” Fleischer says. “And I still think it’s pretty cool.”