A team of scientists has made a remarkable discovery in the tiny 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 researchers an unprecedented glimpse into the ancient animal’s biology.
The last mammoths died out 4,000 years ago, recently enough that some pyramids had already been built in Egypt. For this study, however, the team examined mammoth specimens that are 52,000 and 39,000 years old, respectively, a period when anatomically modern humans still shared the planet with Neanderthals.
Mammoth remains are found across the steppe where they once roamed. The remains of the hairy proboscideans are often preserved in permafrost, permanently frozen topsoil, though thaws and refreezes can damage microscopic structures in the animals’ soft tissues. Sometimes the preservation is astonishing. In 2022, for example, an immaculately preserved mammoth calf was found in a gold mine in the Yukon. 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 deeper, and when we finally zoomed in, we could see that we were in the presence of a new kind of fossil,” study co-author Erez Lieberman Aiden, a computer scientist and geneticist at Rice University, Baylor College of Medicine and the Broad Institute of MIT and Harvard, said at a news conference Tuesday.
How have chromosomes survived for so long?
The 52,000-year-old remains the team examined still had their hair preserved at the millimeter scale, suggesting the woolly mammoth had been flash-frozen. According to the team, this preservation indicates it was frozen about 10,000 years before the Neanderthals went extinct, as the intact hair indicates the skin sample had not thawed since then. So the animal retained its hair, hair follicles, intact cells, and yes, folded chromosomes in their regions of the cell. The research team could actually see the genetic loops that determined whether a particular gene was expressed.
“This sample was freeze-dried, which created a kind of beef jerky,” Leiberman Aiden said. Beef jerky is meat that has undergone a glass transition, which makes it durable. When it was freeze-dried, the mammoth skin became a molecular traffic jam at 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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The quality of the remains allowed for the first genome assembly in an extinct species, the researchers said. Mammoths had 28 chromosomes, just like elephants (and unlike humans, who have 23). The team reconstructed the mammoth chromosomes in 3D; to us, it looks like a Gordian knot. But to researchers, it’s a startlingly close look at the microscopic structures that formed the blueprint for the giants of the Ice Age steppe.
“The variance that you can capture with this mammoth genome opens a new door for comparison across species,” Cynthia Pérez Estrada, a researcher at Baylor College of Medicine and a co-author of the paper, said at the press conference. “Just that footprint of chromatin organization in three-dimensional space is incredible.”
Mammoth ‘beef jerky’ preserved molecular structure of chromosomes intact
The team went to great lengths to destroy the molecular structure of the chromoglass. For their tests, they swapped out the dried-out mammoth hide for dehydrated Boar’s Head beef sausage, which essentially had the same structure on a molecular level. The researchers doused the chromoglass beef in water, acid, and liquid nitrogen; microwaved it, beat it with baseballs and a hammer; ran it over with a car, verbally abused it (“emotionally damaged,” they joked at the press conference) and shot it to pieces with buckshot (seen below). Despite the fragmentation, the chromosomal structure of the stuff remained intact on a microscopic scale.
“They are the first [preserved chromosomes],” Olga Dudchenko, a genomics researcher at Rice University and Baylor College of Medicine and a co-author of the study, said at the news conference. “We suspect that many more will be found in the years to come.”
The new findings reveal previously unseen molecular preservation in ancient remains. While older DNA has been found—a handful of the authors of the new paper were part of the team that published research on the then-oldest preserved DNA, in millions of years old mammoth tusks—the newly described remains made it possible to study how the mammoth’s genes were expressed and its genome was assembled. The current record holder for oldest sequenced DNA belongs to a swath of environmental DNA recovered from northern Greenland, from which the research team was able to reconstruct the ancient environment of the early Pleistocene.
What can scientists do with rapidly frozen chromosomes?
The impeccable preservation of such delicate molecular material could have implications for de-extinction, the process by which some scientific teams and companies attempt to produce proxy species that essentially represent recently extinct animals. In particular, tracking how genes that regulate cold resistance and promote hair growth could be useful for companies trying to engineer 21st-century mammoths. Earlier this year, one such company, Colossal Biosciences, succeeded in creating elephant stem cells, the first to be manipulated in an embryonic state. Still, the team stressed 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, in the context of things like a changing climate,” Leiberman Aiden said. “This is about our ability to learn from the past.“
AI can help unfold the tree of life
The woolly mammoth’s closest living relative is the Asian elephant. Scientists can better understand elephant genetics using mammoth chromosomes. But elephant genetics can also help scientists understand mammoths. Scientists can feed AI models a string of genetic code and ask the AI where proteins were likely bound in the mammoth, or how the genome is likely folded.
“Even a handful of data points about mammoths, when fed into these AIs, can yield a wealth of information,” Lieberman Aiden told Gizmodo. In addition to the Asian elephant, AI tools can contextualize the mammoth genome within the tree of life. “The great power of AI is its ability to take insights from all those species and synthesize them to give you pretty good guesses,” Lieberman Aiden added.
A combination of new technologies, inventive methods, and luck is revealing the ancient world on scales previously unheard of. Understanding the giant mammoth on a molecular scale helps us understand the ancient past, but also helps inform the conversation about existing animals for the future.