Freeze-drying turned a woolly mammoth’s DNA into 3-D ‘chromoglass’

The elaborate study of nan mammoth genome was made imaginable aft an world squad of scientists figured retired really to accommodate a method dubbed Hi-C to analyse ancient DNA (SN: 8/24/15).  

“I’ve known astir Hi-C for a while now. I conscionable ne'er could deliberation of a measurement that you would use it to ancient DNA,” says Christina Warinner, a biomolecular archaeologist astatine Harvard University who was not progressive successful nan study.

That’s because DNA crumbles complete time. It was difficult to ideate that nan mini bits of ancient DNA could clasp nan style of chromosomes, Warinner says. And Hi-C, which is utilized for looking astatine nan 3-D building of meters of DNA packed into a cell’s nucleus, usually requires fresh, intact samples (SN: 6/10/21).

Even Pérez Estrada’s colleagues, who activity connected 3-D DNA building astatine Baylor College of Medicine successful Houston, weren’t convinced specified techniques could activity connected degraded samples. Pérez Estrada thought it could, truthful she tested Hi-C connected turkey bones near complete aft Thanksgiving dinner, connected insubstantial from a dried-out roadkill rodent she recovered connected her measurement to work, and connected a portion of leather from her bag.

“All of those experiments were fascinating, because it really showed that nan building of nan DNA is beautiful resilient,” she says. “And contempt nan cooking, and contempt nan sun and nan situation erstwhile talking astir nan mouse, nan building of nan DNA was still there.”

But she didn’t cognize whether nan building could clasp up for thousands of years. So she teamed up pinch Marcela Sandoval-Velasco, past astatine nan University of Copenhagen. Sandoval-Velasco had been moving connected ancient DNA for years and was willing successful probing 3-D structures. She brought “a container afloat of wonders” — depository specimens of ants, bees, coelacanths, fish, reptiles, birds and animals — to Houston for testing, Perez Estrada says. And Pérez Estrada visited Copenhagen, wherever nan researchers probed ancient polar carnivore skulls and a mummified wolf.

The experiments often failed. The Hi-C method utilized connected caller samples wouldn’t activity for ancient samples, truthful a caller type — which they called PaleoHi-C — had to beryllium invented. That’s research, says Sandoval-Velasco, who is now astatine nan National Autonomous University of Mexico successful Cuernavaca. “It goes slow. It’s iterative. It’s afloat of failures, and it’s astir not giving up.” Teamwork helps too, she says. More than 50 scientists pinch different areas of expertise came together for nan study.

After years of partial occurrence and failure, nan squad sewage entree to tegument from nan caput of a woolly mammoth that died successful Siberia astir 52,000 years ago. The mammoth was freeze-dried and preserved successful permafrost.

Rapid drying had locked nan ancient DNA into a tight molecular authorities akin to that of glass, called chromoglass. The geneticists and a squad of theoretical physicists deduced that nan chromoglass building prevented nan pieces of DNA from drifting distant from each other.  

In unconventional experiments pinch lab-made beef jerky, nan squad recovered that specified glassy DNA tin stay unchangeable for astatine slightest a twelvemonth astatine room somesthesia and guidelines up to varied insults including being microwaved, tally complete pinch a car, smashed pinch a fastball and blasted pinch a shotgun.

Permafrost and freeze-drying preserved DNA of a woolly mammoth that died 52,000 years agone (a ft shown here, foreground) successful a reliable molecular building called chromoglass.Love Dalén/Stockholm University.

The mammoth’s glassy DNA locked its chromosomes into place. For nan first clip nan researchers could count nan number of chromosomes a mammoth has — 28 pairs, conscionable for illustration elephants, Erez Lieberman Aiden, a geneticist astatine Baylor College of Medicine, said during a news convention July 2. Mammoths besides person nan aforesaid basal chromosome building arsenic elephants.

Chromosomes stuffed into nan nucleus lucifer a skein of yarn aft a feline has played pinch it. The snaggled quality belies nan cautiously orchestrated building within.

Genes that are turned connected are moved to 1 subcellular compartment for illustration dancers taking nan creation floor, while genes that will beryllium turned disconnected are relegated to wallflower position successful different compartment. Examining nan compartments, nan researchers recovered 425 genes that were progressive successful mammoths but not successful elephants and 395 genes turned connected successful elephants but not mammoths.

Those see a cistron called Egfr, which helps modulate tegument and hairsbreadth growth. In elephants nan cistron was active, but was a wallflower successful mammoths. In people, switching disconnected nan cistron leads to long, heavy eyelashes and excessive hairsbreadth growth. That suggests that keeping nan cistron disconnected nan creation level whitethorn person helped mammoths turn their agelong shaggy coats.

The squad examined nan DNA of a 2nd mammoth that was killed by a saber-toothed tiger astir 39,000 years agone and buried by quality hunters, astir apt to sphere nan meat. The hunters ne'er went backmost for their prize, Aiden said, but nan researchers recovered that nan mammoth besides had chromoglass that preserved loops, compartments and different 3-D structures successful nan DNA. Quick drying by freezing aliases precocious temperatures mightiness nutrient akin DNA solid successful different earthy aliases created mummies, nan squad suggests.

Warinner predicts that “a batch of scientists are going to publication this and commencement to think, ‘Could we use [PaleoHi-C] to our ain questions? Could this lick questions aliases problems that we person been stuck connected for a agelong time?’”

There will beryllium a learning curve to use a method that researchers who study ancient DNA didn’t moreover cognize they could use, she says. The study “opens up a batch of caller doors successful nan field, successful a guidance that we conscionable haven’t been looking before,” she adds. “I deliberation it’s really exciting.”