On the frozen tundra of Siberia about 50,000 years ago arrived Woolly mammoth his end under mysterious circumstances. In samples of the animal's skin, researchers have now discovered chromosomes that have been preserved in their original 3D configuration 1– an achievement that was previously considered impossible in DNA research with fossil DNA.

The team also revealed the spatial organization of the mammoth's DNA molecules and the active genes in its skin, including a gene that gives the animal its fluffy appearance. The work was done todayCellpublished.

The study is the first to report the 3D structure of an ancient genome, says Ludovic Orlando, a molecular archaeologist at Paul Sabatier University in Toulouse, France, who was not involved in the research. Because the spatial structure of a genome—the complete set of an organism's genetic material—provides clues about gene activity, understanding this structure could provide deeper insights into the cellular biology of mammoth skin than simply examining the DNA sequence alone, he says. “This work is simply unprecedented.”

Destruction through time

About 40 years ago, scientists discovered that remnants of DNA could survive in samples from the distant past, including Egyptian mummies thousands of years old. It has since become apparent that DNA has been preserved in many ancient remains.

As time passes, DNA degrades and suffers chemical damage, so researchers had previously only obtained DNA fragments that had no coherent structure, says study co-author Erez Lieberman Aiden, a geneticist at Baylor College of Medicine in Houston, Texas. Reconstructing a 3D genome from such pieces is almost impossible: a mammalian genome is 30 million times larger than a typical fragment of ancient DNA, he says.

Amazing discovery

Challenging this assumption, Lieberman Aiden and his colleagues began a nine-year search for well-preserved ancient samples and eventually found nearly intact chromosomes in 52,000-year-old skin samples from a woolly mammoth (Mammuthus primigenius), which came from the Siberian permafrost. The discovery was “simply breathtaking,” says study co-author Cynthia Pérez Estrada, a geneticist at Baylor College of Medicine.

The legs of a juvenile female wooly mammoth, with a gloved hand holding a tuft of ginger hair at the foot

The researchers analyzed the structure of the mammoth's chromosomes and revealed the folding of the DNA molecule and its spatial organization in the cell nucleus - two features that determine which genes are switched on and for how long.

Compare with modern elephants, the mammoth's closest living relatives, showed not only similarities in chromosome number and structure, but also differences in the activity of genes involved in hair growth and cold adaptation.

Freeze-dried DNA

The researchers suggested that the mammoth chromosomes were preserved in a glass-like state through a dehydration process similar to that used to make beef jerky. This technique results in a tissue in which the DNA molecules are tightly packed and immobile.

The team's experiments on freeze-dried beef jerky, which was subjected to extreme tests such as being shot at with a gun and run over by a car, confirmed the researchers' theory: The jerky shattered like glass, but its chromosomes remained intact.

“In no way would you think that [ancient] DNA would be preserved in its form,” says Víctor Moreno Mayar, a specialist in genomics of ancient populations at the University of Copenhagen, who was not involved in the study. Seeing that she can do it “is really cool,” he says.

The results suggest that the potential for restoring ancient DNA goes beyond what was previously thought possible, provided the conditions are ideal, says Moreno Mayar.

The approach in the paper could also help researchers assemble a complete mammoth genome, says Eriona Hysolli, head of life sciences at Colossal Biosciences, a biotechnology company in Dallas, Texas, that is working to revive the woolly mammoth.

Hysolli, who was not involved in the study, says a complete mammoth genome could help reveal traits that could be relevant to the company's bold plan - the creation of an elephant-mammoth hybrid, which resembles the extinct animal and could be reintroduced into its natural habitat.