Oldest RNA sample ever recovered from a woolly mammoth

A woolly mammoth frozen in Siberian permafrost for almost 40,000 years produced the world’s oldest RNA.

The specimen, discovered in 2010 and nicknamed Yuka, is considered the best preserved woolly mammoth (The original mammoth) never found. Yuka was originally thought to be a young female who died, perhaps after being attacked by cave lions, between 6 and 8 years old.

Scientists have already been able to recover DNA from numerous woolly mammoths, some of which are more than a million years old. The reconstruction of their genome has raised hopes that one day these species – or genetically modified animals that resemble mammoths – could be brought back to life through genetic engineering.

DNA codes the genetic instructions for making proteins in all animals. When a particular gene is turned on, the DNA code is transcribed into another molecule called RNA. RNA is much less stable than DNA and typically degrades within hours of death.

So far, the oldest RNA ever discovered came from a wolf preserved in Siberian permafrost more than 14,000 years ago. Now, Love Dalén of Stockholm University in Sweden and colleagues have successfully extracted RNA from one of Yuka’s legs, almost triple the previous record.

The team used the same techniques used to obtain RNA samples from fresh, modern specimens, but modified them slightly to recover much smaller and older molecules.

“Yuka is exceptionally well preserved,” says Dalén. “The specimen likely underwent rapid freezing and long-term burial in permafrost, as evidenced by the preservation of muscle tissue and woolly fur. This greatly increases the chances of RNA preservation.”

However, the fact that Yuka was allowed to thaw briefly during transport from where the remains were discovered in northeastern Siberia to Yakutsk worked against the team. “Our hypothesis was that any truly ancient RNA still present in our samples would be degraded and fragmented into small pieces,” says Dalén.

The team had to take exceptional precautions to preserve all of their samples from further deterioration and also prevent contamination. “We used liquid nitrogen to grind the samples, along with sterile materials, a filtered air atmosphere, protective suits and a controlled laboratory environment to avoid any modern external sources of contamination in our sequencing data,” he explains.

RNA sequencing can give an indication of which genes were activated at the time the animal died. In the RNA the team isolated from Yuka’s muscle and skin, they found signs of genetic activity linked to muscle metabolism and cellular stress – consistent with the idea that Yuka died during a cave lion attack.

One of the big surprises was that, through a combination of DNA and RNA analysis, the team is now certain that Yuka was actually a man. “I’ve been around long enough to know these things happen,” Dalén says. “Yuka is well preserved for being 40,000 years old, but is not completely intact, so it is not always easy to morphologically sex an individual.”

The researchers also looked for RNA viruses such as influenza and coronaviruses, but found nothing of interest. “But I think we will see several studies of Ice Age RNA viruses in the future,” says Dalén. “There are, for example, Pleistocene bird carcasses that would be very interesting to study with regard to avian flu. »

The RNA sequences recovered in the study are not directly relevant to causing mammoth deextinction, says Dalén, scientific advisor to Colossal Biosciences, the company that claimed earlier this year to have brought the dire wolf back from extinction. But the study can provide useful information about which genes are important for the development of certain traits, he says. “The RNA profiles of mammoths could in the future tell us how certain traits, like mammoth hair, were genetically controlled.”

Merlin Crossley, of the University of New South Wales in Sydney, says obtaining such ancient RNA is a remarkable achievement, but the results don’t tell us much about mammoth biology. “It’s a bit like flying a light plane under the Sydney Harbor Bridge,” he says. “It’s an impressive technical feat, but I’m not sure what we learned from it.”

Crossley believes that although older RNA samples may be discovered in the future, the team is close to the extreme limit of how long RNA can survive. He says it is also unlikely that useful information will be obtained from other mammoths, because specimens like Yuka are very rare.

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