52,000-Year-Old Mammoth

‘Beef Jerky’ Reveals

Exquisitely Preserved
Chromosomes
The delicate biological structures were miraculously preserved, giving
scientists a time capsule into the genomic architecture of the extinct
giants.

By Isaac Schultz
Published July 11, 2024 | Comments (3)

A crack team of scientists has made a remarkable discovery in the small

molecules of a giant creature: immaculately preserved genome architecture in
the 52,000-year-old remains of a woolly mammoth. The desiccated skin is so
well preserved that it contains intact mammoth chromosomes, giving the
researchers an unprecedented look into the ancient animal’s biology.

The last mammoths went extinct 4,000 years ago, recent enough that some of
the pyramids were already built in Egypt. For this study, however, the team
investigated mammoth samples that date back 52,000 years and 39,000
years, respectively, at which point anatomically modern humans still shared
the planet with Neanderthals.

Mammoth remains are found across the steppe on which they once roamed.
The hairy proboscideans’ remains are often preserved in permafrost—
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 permanently frozen topsoil—though phases of thawing and refreezing can
damage the microscopic structures in the animals’ soft tissue. Sometimes, the
preservation is stunning. In 2022, for example, an immaculately preserved
mammoth calf was found in a Yukon gold mine. But the recent discovery
revealed preservation on an entirely different scale: a molecular one. The
team’s research was published today in Cell.

“We looked around, we dug down, and as we finally zoomed in, we could see
that we were in the presence of a new kind of fossil,” said study co-author Erez
Lieberman Aiden, a computer scientist and geneticist affiliated with Rice
University, Baylor College of Medicine, and the Broad Institute of MIT and
Harvard, in a press conference last Tuesday.

Mammoth skin, in which mammoth chromosomes were found. © Photo by Love Dalén, Stockholm University
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 How did chromosomes survive for so long?

The 52,000-year-old remains investigated by the team still retained its hair at
the millimeter scale, which suggests that the woolly mammoth was flash-
frozen. According to the team, this preservation indicates that it froze
approximately 10,000 years before the Neanderthals went extinct, as the
intact hair signifies that the skin sample did not undergo any thawing since
then. Thus, the animal retained its hair, follicles, intact cells, and yes, folded
chromosomes within their regions of the cell. The research team could
actually see the genetic loops that managed whether a certain gene was
expressed.

“This sample freeze dried, forming a kind of beef jerky,” Leiberman Aiden
said. Beef jerky is meat that’s undergone glass transition, making it durable.
When it freeze-dried, the mammoth skin became a molecular traffic jam on
the microscopic level where the chromosomes couldn’t diffuse. The skin
samples became time capsules for the ancient molecules, and the team
dubbed the flash-frozen genetic material “chromoglass.”
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 A 3D animation of the mammoth chromosomes.
Gif: Vinicius Contessoto, Antonio Oliveira Jr., José Onuchic

The quality of the remains enabled the first genome assembly in an extinct
species, the researchers said. Mammoths had 28 chromosomes, just like an
elephant (and unlike us humans, who have 23). The team reconstructed the
mammoth chromosomes in 3D; to us, it looks like a Gordian knot. But to
researchers, it is an astoundingly precise glimpse at the microscope structures
that blueprinted the giants of the Ice Age steppe.

“The variance that you’re able to capture with this mammoth genome is
opening a new door for comparison between species,” said Cynthia Pérez
Estrada, a researcher at Baylor College of Medicine and co-author of the
paper, in the press conference. “Just having that footprint of the chromatin
organization in three-dimensional space is incredible.”
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 Mammoth ‘beef jerky’ kept the chromosomes’ molecular
structure intact

The team did everything they could to try and obliterate the molecular
structure of the chromoglass. For their tests, they swapped out the desiccated
mammoth skin for dehydrated Boar’s Head beef bologna, which for all intents
and purposes had the same structure on a molecular level. The researchers
dipped the chromoglass beef in water, acid, and liquid nitrogen; they
microwaved it, hit it with baseballs and a mallet; they ran it over with a car,
bullied it verbally (“emotionally damaged it,” they joked in the press
conference), and blasted it with shotgun shells (seen below). Despite the
material becoming fragmented, the chromosomal structure of the stuff
remained intact on a microscopic scale.

© Aviva Aiden, Thomas Griggs, Erez Aiden

“They are the first [preserved chromosomes],” said Olga Dudchenko, a

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 genomics researcher at Rice University and Baylor College of Medicine and
co-author of the research, in the press conference. “We suspect many more
will be found in the coming years.”

The new findings reveal never-before-seen molecular preservation in ancient

remains. While older DNA has been found—indeed, a handful of authors on
the new paper were part of the team that published research on the then-
oldest preserved DNA, in million-year-old mammoth tusks—the newly
described remains made it possible to study how the mammoth’s genes were
expressed and its genome assembled. The current record-holder for oldest
sequenced DNA belongs to a swathe of environmental DNA recovered from
northern Greenland, and from which the research team was able to
reconstruct the ancient environment of the early Pleistocene.

What can scientists do with ?ash-frozen chromosomes?

The immaculate preservation of such delicate molecular material may have

implications for de-extinction, the process by which some scientific teams and
companies are attempting to produce proxy species that for all intents and
purposes represent recently extinct animals. Specifically, tracking how genes
that regulate cold resistance and promote hair growth could be useful for
companies attempting to build 21st-century mammoths. Earlier this year, one
such company—Colossal Biosciences—managed to create elephant stem cells,
the first engineered into an embryonic state. Nevertheless, the team
emphasized that de-extinction is a difficult process and not the goal of their
research.

“We are a very powerful species on a very small planet, making important
decisions about the future of our species and the future of life on this planet,
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 in the setting of things like a changing climate,” Leiberman Aiden said. “This
is about our ability to learn from the past.“

AI can help unpack the tree of life

The closest living relative to the woolly mammoth is the Asian elephant.
Scientists can better understand elephant genetics using mammoth
chromosomes. But so too can elephant genetics inform scientists’
understandings of the mammoth. Scientists can offer AI models a strand of
genetic code and ask the AI where proteins were likely bound in the
mammoth, or how the genome is likely folded.

“Even a smattering of data about mammoths when fed into these AIs can lead
to a wealth of information,” Lieberman Aiden told Gizmodo. Besides the Asian
elephant, AI tools can contextualize the mammoth genome on the tree of life.
“The great power of AI is its ability to take insights from all of those species
and synthesize them in order to give you pretty good guesses,” Leiberman
Aiden added.

A combination of new technologies, inventive methods, and good fortune is

revealing the ancient world on scales previously unheard of. Understanding
the massive mammoth on molecular scales helps our understanding of the
ancient past, but also helps the conversation of extant animals for the future.
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