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New woolly mammoth chromosome discovery could help with resurrection efforts

The new finding could give insight into more than just the prehistoric animal’s genetic code.

More than 10,000 years ago, mammoths once roamed Texas. Herds of these lumbering, small-eared giants — called Columbian mammoths — with their long, curved tusks were a likely sight to behold grazing the once lush grasslands blanketing north and central Texas.

In a paleontological first, scientists are potentially closer to understanding the genetics of these prehistoric animals through another long-lost relative, the woolly mammoth.

A group of scientists led by the Baylor College of Medicine reconstructed woolly mammoth chromosomes from a 52,000-year-old female well-preserved by the Siberian permafrost. Using an innovative genome sequencing technique dubbed PaleoHi-C, the researchers determined woolly mammoths sported 28 pairs of chromosomes (for reference, humans have 23 pairs) and what the 3D structure of these chromosomes looks like.

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These findings, which were published Thursday in the journal Cell, lend insight into more than just a mammoth’s genetic code, said Vincent Lynch, an associate professor of biological sciences at the University at Buffalo in New York. Lynch has investigated mammoth genomes but was not involved in the new study.

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“Without this kind of data, we would never really have a complete picture of what other kinds of changes make mammoths look like mammoths,” Lynch said. “This [study] gives us a whole new level of information.”

Uncovering ancient genes with 3D pictures

While sequencing ancient DNA is possible — it’s been done for mummies and many archaic human and prehistoric animal species — a major hurdle is that DNA crumbles as it ages.

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“DNA is a double-helix with molecules of phosphate [as a] backbone, you think of it as a spine of a book,” said Erez Lieberman Aiden, director of the Center for Genome Architecture at the Baylor College of Medicine, who led the study. “What happens over time is that the spine gets ripped apart, so suddenly, instead of a chromosome with 100 million letters, you have millions of fragments of dozens or hundreds of letters.”

Reassembling these DNA fragments in their original line-up can be incredibly difficult, especially given the fact that DNA has long stretches of repetitive letters that are hard to distinguish from one another and accurately place.

An artist's interpretation of chromatin - the mixture of DNA and proteins that form...
An artist's interpretation of chromatin - the mixture of DNA and proteins that form chromosomes - folded up inside the nucleus. The artist has rendered an extraordinarily long contour into a small area, in two dimensions, by hand.(Mary Ellen Scherl / Mary Ellen Scherl)
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In 2009, Aiden and colleagues at the Broad Institute of Harvard and MIT and the University of Massachusetts Medical School developed a way to take 3D snapshots of the human genome. Dubbed Hi-C, this technique later proved useful in DNA sequencing. For instance, it was used to map out the genome of Aedes aegypti mosquitoes responsible for spreading Zika virus, and a goat named Papadum descended from a rare goat population that once inhabited an island off the coast of southern California.

“If I can produce a 3D map, I can get the genome assembled, I can figure out the number of chromosomes, I can figure out all the genes,” Aiden said. “It’s a one-stop shop.”

Hi-C worked well enough if you started off with fresh, intact biological samples. But whether it could work for degraded or ancient DNA was unclear.

In 2015, Aiden and his colleague Olga Dudchenko, an assistant professor of molecular and human genetics at Baylor College of Medicine, teamed up with other scientists in Europe to explore this question.

The group tried Hi-C on myriad ancient animal samples, along with some not-so-ancient ones like Thanksgiving turkey bones, beef jerky and even roadkill.

While their experiments often failed, the researchers struck gold with a well-preserved 52,000-year-old female mammoth discovered in Siberia in 2018. They scraped skin cells from the mammoth’s shaggy head and realized that the cold temperatures freeze-dried the tissue, preventing the DNA fragments from drifting apart.

“From a physics standpoint, what’s happening is known as a glass transition,” said Dudchenko. When biological tissues rapidly lose water, whether from freeze- or hot-drying, the process appears to keep DNA fragments in place and preserves the genome’s 3D structure. “The resulting ‘chromaglass,’ which is this fancy word we’ve coined, can indeed stay very stable for long periods of time,” she added.

52,000-year-old woolly mammoth skin after it was excavated from permafrost. The Cell study...
52,000-year-old woolly mammoth skin after it was excavated from permafrost. The Cell study shows that fossils of ancient chromosomes survive in the skin.(Love Dalén / Love Dal?n/Stockholm University)
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PaleoHi-C, a more finessed technique than the original, revealed the woolly mammoth had 28 pairs of chromosomes, just like its closest living relative, the elephant. The researchers compared which genes were turned on and off between the two animals: 425 were active in woolly mammoths but not in elephants, whereas 395 were active in elephants but not in woolly mammoths.

Among those genes active in elephants but not mammoths is EGFR. This gene can lead to excessive hair growth when it’s turned off, which may explain the mammoth’s hairy coat and adaptation to cold environments.

The researchers also examined the DNA of a second female mammoth, nicknamed Yuka, who died 39,000 years ago and was freeze-dried by the Siberian permafrost, achieving that chromaglass state.

‘Resurrecting’ the woolly mammoth

Uncovering these mammoth chromosomes and their 3D structure holds great promise for companies like Deep Ellum-based Colossal Biosciences in its bold plan to “resurrect” the woolly mammoth.

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In March, Colossal Biosciences announced it had made a “momentous step” forward by reprogramming Asian elephant cells, which could potentially be programmed into mammoth cells by modifying which shared genes are turned off and on. Asian elephants are the woolly mammoth’s closest relative, even closer than African elephants.

“It’s exciting to see that 3D architecture can be preserved in ancient samples,” said Eriona Hysolli, head of biological sciences at Colossal, in an email. “This [study] will help move toward a complete [new] assembled mammoth genome, which could reveal features of the genome that might be relevant to mammoth de-extinction.”

Lynch of the University at Buffalo and Ron Tykoski, a paleontologist and vice president of science at the Perot Museum of Nature and Science, said the findings could yield insights into other mammoth species, like Texas’ Columbian mammoth.

It was first thought that Columbian mammoths were the descendants of woolly mammoths that evolved in North America after crossing the Bering Land Bridge millions of years ago, Tykoski said. “As it turns out, when people were finally able to get some pretty good gene sequences off of Columbian mammoths, they found that Columbian mammoths were actually a hybrid between woolly mammoths and an unknown, never identified population of some other mammoth somewhere else in Asia.”

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While well-preserved Columbian mammoth remains like that of the Siberian woolly mammoth are yet to be found, Aiden and Dudchenko hope their group’s discoveries — both of chromaglass and PaleoHi-C’s success — will help scientists peer into an untapped genetic historical record.

“The primary goal of this study has not been motivated by [bringing back the mammoth],” Dudchenko said. “We believe this is a way to learn about ancient species and a new way to allow us to gain biological insights to learn more broadly from the past… and to apply this knowledge looking forward, to become better stewards of life on Earth.”

Miriam Fauzia is a science reporting fellow at The Dallas Morning News. Her fellowship is supported by the University of Texas at Dallas. The News makes all editorial decisions.