Scientists build first 3D genome of extinct animal using freeze-dried woolly mammoth

A photo of a mammoth foot in a permafrost environment. A study shows that the morphology of ancient chromosomes is preserved in mammoth permafrost samples from 52,000 years ago, enabling the genome assembly and transcriptomic analysis of extinct species. (Photo: Love Dalén, Stockholm University)

By Elsabé Brits

11 Jul 2024

About 52,000 years ago, a woolly mammoth died in the icy landscape of what is today Siberia. The body freeze-dried shortly afterwards, preserving the DNA in a near-perfect glass-like state – like a dehydrated piece of biltong – until it was discovered.

An international research team has assembled the genome and 3D chromosomal structures of a 52,000-year-old woolly mammoth – a first for any ancient DNA sample.

The unique way the mammoth was preserved – much like a freeze-dried, dehydrated piece of biltong – is the secret to the level of structural genetic detail the team was able to find.

The results are published in the journal Cell.

“This is a new type of fossil, and its scale dwarfs that of individual ancient DNA fragments – a million times more,” said corresponding author Erez Lieberman Aiden, director of the Center for Genome Architecture at Baylor College of Medicine.

The team also used a second mammoth, from Siberia, to add detail to the picture. This juvenile died 39,000 years ago when it was caught by a sabre-toothed cat. Early humans took the carcass and buried it. Their “buried treasure” remained there until it was found by this team of researchers.

mammoth genome The 52,000-year-old wooly mammoth skin after it was excavated from permafrost. The Cell study shows that fossils of ancient chromosomes survive in the skin. (Photo: Love Dalén, Stockholm University)

Most ancient DNA specimens consist of very small, scrambled DNA fragments. But because mammoth was not mineralised, like other typical fossils, the genetic material was in a glass-like state. The skin and hair were superbly intact.

Aide told the media the mammoth was “beautiful, its hair was still on it with metres of skin still attached. Finally, you have to zoom in, you see at the millimetre scale it never thwarted in all these years. The cells were intact, and that is when we became excited. And even further, the chromosomes were still in their territories. The chromosomes were folded like in the original mammoth… And the genes in their on and off configuration were present.”

This is what the team calls “fossil chromosomes… still in their original arrangements”.

The way the genetic material was preserved was like “chromosome glass. All those molecules are so densely packed in there that there is nowhere for them to go. They cannot diffuse at all. And that makes… a time capsule of the geometry of the ancient molecules.”

This is how it became much like frozen biltong, which the international team, of course, called beef jerky.

To reconstruct the mammoth’s genomic architecture, the researchers extracted DNA from a skin sample taken behind the “oldest” mammoth’s ear. They used a method called Hi-C which allows them to detect which sections of DNA are likely to be in close spatial proximity and interact with each other in their natural state in the nucleus.

They discovered the woolly mammoth had 28 chromosomes just like Asian and African elephants. By examining the compartmentalisation of genes within the nucleus the researchers were able to identify genes that were active and inactive within the mammoth’s skin cells – a proxy for epigenetics or transcriptomics.

The mammoth skin cells had distinct gene activation patterns compared with the skin cells of its closest relative, the Asian elephant, including genes related to its woolly-ness and cold tolerance.

Legs of a juvenile female wooly mammoth named Yuka. She was killed by a sabre-toothed cat 39,000 years ago. (Photo: Love Dalén, Stockholm University)

“Imagine you have a puzzle that has three billion pieces, but you don’t have the picture of the final puzzle to work from,” said corresponding author Marc Marti-Renom, a genomicist at Centre for Genomic Regulation in Barcelona.

Olga Dudchenko from the Center for Genome Architecture at the Baylor College of Medicine said one of the unique features of the mammoth is that it looks “like Chris Waddle the [former] football player”.

It took the team nine years not only to find the perfect sample but to move from one-dimensional reconstruction to 3D.

They tested anything they could get their hands on, “from our Thanksgiving dinner, to roadkill to museum samples”, to finally seeing the mammoth genome in 3D. It was mind-blowing, said Cynthia Pérez Estrada, one of the researchers.

It may be that other samples also have this glassy structure, including museum collections. There are more ways to obtain a glassy state during natural preservation, for example in Egyptian mummies.

A mammoth foot in a permafrost environment. A study shows that the morphology of ancient chromosomes is preserved in mammoth permafrost samples from 52,000 years ago, enabling the genome assembly and transcriptomic analysis of extinct species. (Photo: Love Dalén, Stockholm University)

The reasons woolly mammoths died out are still unclear. The last population was isolated on Wrangel Island off the coast of Siberia 10,000 years ago, when sea levels rose and cut off the mountainous island from the mainland.

Another recent genomic analysis reveals that the isolated mammoths, who lived on the island for the subsequent 6,000 years, originated from, at most, eight individuals but grew to between 200 and 300 individuals within 20 generations.

“We can now confidently reject the idea that the population was simply too small and that they were doomed to go extinct for genetic reasons,” says senior author Love Dalén, an evolutionary geneticist at the Centre for Palaeogenetics in Sweden.

“This means it was probably just some random event that killed them off, and if that random event hadn’t happened, then we would still have mammoths today.” DM

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