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—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.
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.”
Gif: Vinicius Contessoto, Antonio Oliveira Jr., Jose 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.”
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.
“They are the first [preserved chromosomes],” said Olga Dudchenko, a 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 flash-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, 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.
