Turning Woolly Mammoth DNA into 3D ‘Chromoglass’ through Freeze-Drying Innovation

Researchers Uncover Remarkably Preserved 52,000-Year-Old Mammoth Skin with Intact 3D DNA Structure

Imagine if beef jerky and woolly mammoths had something surprising in common: the process of drying transforms their DNA into a remarkably durable glass-like state.

This remarkable glassy DNA, as reported in Cell on July 11, has preserved the three-dimensional structure of a woolly mammoth’s chromosomes for an astonishing 52,000 years. Genomicist and neuroscientist Cynthia Pérez Estrada explains that this discovery offers unprecedented insights into the genetic blueprint of the extinct mammoth, even revealing which genes were active at the time of its death. If more well-preserved specimens are found, scientists could better understand the functionality of extinct organisms, not just their appearance.

“I’ve known about Hi-C for a while now but never imagined applying it to ancient DNA,” says Christina Warinner, a biomolecular archaeologist at Harvard University who wasn’t involved in the study.

DNA tends to degrade over time, making it hard to believe that ancient fragments could retain the structure of chromosomes. Hi-C, a technique used to study the 3D arrangement of DNA within a cell's nucleus, typically requires fresh, intact samples.

Pérez Estrada’s team at Baylor College of Medicine was skeptical that such methods could work on degraded samples. Undeterred, she experimented with Hi-C on various specimens, including turkey bones from Thanksgiving dinner, a dried-out roadkill mouse, and a piece of leather from her bag.

“These experiments were fascinating because they demonstrated the resilience of DNA structure despite harsh conditions,” she says. “Even after cooking, sun exposure, and environmental factors, the DNA structure remained intact.”

To test whether this structure could endure for millennia, Pérez Estrada collaborated with Marcela Sandoval-Velasco, an expert in ancient DNA. Sandoval-Velasco, then at the University of Copenhagen, brought a variety of ancient specimens to Houston for testing, including ants, bees, coelacanths, reptiles, birds, and mammals. Pérez Estrada also visited Copenhagen to examine ancient polar bear skulls and a mummified wolf.

Many initial attempts failed, leading to the development of a new method called PaleoHi-C. Sandoval-Velasco, now at the National Autonomous University of Mexico, emphasized the iterative nature of research, full of setbacks and the importance of perseverance and teamwork. Over 50 scientists contributed their expertise to the study.

After years of effort, the team obtained skin from a 52,000-year-old woolly mammoth found in Siberia, preserved in permafrost. The rapid drying process had locked the DNA into a glass-like state known as chromoglass. This structure prevented DNA fragments from drifting apart, allowing researchers to analyze the genome in unprecedented detail.

Unconventional experiments with lab-made beef jerky revealed that such glassy DNA can remain stable for at least a year at room temperature and withstand various forms of abuse, including microwaving, being run over, smashed with a fastball, and even blasted with a shotgun.

The researchers discovered that the mammoth had 28 pairs of chromosomes, just like modern elephants, as revealed by geneticist Erez Lieberman Aiden of Baylor College of Medicine during a press conference on July 2. The overall chromosome structure of mammoths closely resembled that of elephants.

Chromosomes in a cell’s nucleus resemble a tangled skein of yarn, yet they maintain a highly organized structure. Active genes occupy specific compartments like dancers on a dance floor, while inactive genes remain in separate areas. The researchers identified 425 genes active in mammoths but not in elephants, and 395 genes active in elephants but not in mammoths.

One notable gene, Egfr, which regulates skin and hair growth, was inactive in mammoths but active in elephants. In humans, turning off this gene results in long, thick eyelashes and excessive hair growth, suggesting that its inactivity may have contributed to the mammoth’s shaggy coat.

The team also examined DNA from a second mammoth, which had been killed by a saber-toothed tiger around 39,000 years ago and buried by human hunters. This mammoth's DNA also formed chromoglass, preserving its 3D structure. The researchers speculate that quick drying by freezing or high temperatures might produce similar DNA glass in other natural or created mummies.

Warinner predicts that this breakthrough will inspire many scientists to consider applying PaleoHi-C to their own research questions, potentially solving long-standing mysteries in ancient DNA studies. “This study opens up a lot of new doors in the field, in a direction we haven’t looked before,” she says. “It’s really exciting.”

4o