Oldest ever RNA sample recovered from woolly mammoth

A woolly mammoth that has lain in Siberian permafrost for nearly 40,000 years has discovered the world's oldest RNA.

The specimen, found in 2010 and nicknamed Yuka, is considered the best-preserved woolly mammoth.Original mammoth) ever found. Yuka was initially thought to be a young female who died, possibly after being attacked by cave lions, between the ages of 6 and 8.

Scientists have already obtained the DNA of many woolly mammoths, including some. over a million years old. Reconstruction of their genomes has raised hopes that one day species – or genetically engineered animals similar to mammoths – could be brought in return to life using genetic engineering.

DNA encodes 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 usually degrades within a few hours of death.

Until now, the oldest RNA ever discovered belonged to a wolf and was preserved in the permafrost of Siberia. more than 14,000 years ago. Now, Lyubov Dalen from Stockholm University in Sweden and his colleagues were able to extract RNA from one of Yuki's legs, almost three times the previous record.

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

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

However, working against the team was the fact that Yuka was allowed to thaw briefly during transport from the site where the remains were discovered in northeastern Siberia to Yakutsk. “We assumed that any truly ancient RNA still present in our samples would be destroyed and fragmented into small pieces,” says Dahlen.

The team had to take extreme care to preserve all of their samples from further deterioration, as well as prevent contamination. “We used liquid nitrogen to grind the samples, as well as sterile materials, a filtered air atmosphere, protective suits, and a controlled laboratory environment to avoid any source of external modern contamination in our sequencing data,” he says.

RNA sequencing can provide insight into which genes were turned on when the animal died. In the RNA the team isolated from Yuka's muscle and skin, they found evidence of activity in genes related to muscle metabolism and cellular stress, consistent with the idea that Yuka died in a cave lion attack.

One of the big surprises was that, thanks to a combination of DNA and RNA analysis, the team is now confident that Yuka was in fact male. “I’ve lived here long enough to know that these things happen,” Dahlen says. “Yuka is well preserved and 40,000 years old, but it is not completely intact, so morphologically determining the sex of an individual is not always easy.”

The researchers also looked for any RNA viruses, such as influenza and coronaviruses, but didn't find anything interesting. “But I think we will see some studies of Ice Age RNA viruses in the future,” Dahlen says. “There are, for example, some Pleistocene bird carcasses that would be very interesting to examine for avian influenza.”

The RNA sequences discovered in the study are not directly related to the mammoth resurgence, says Dahlen, a scientific consultant for Colossal Biosciences, a company that earlier this year claimed that brought the dire wolf back from extinction. But the study could provide useful information about which genes are important for the development of certain traits, he says. “RNA profiles of mammoths could in the future tell us how certain traits, such as mammoth hair, are controlled genetically.”

Merlin Crossley from the University of New South Wales in Sydney say that obtaining such ancient RNA is a remarkable achievement, but the results tell us little about the biology of the mammoth. “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 while older RNA samples may be found in the future, the team is close to the extreme limit of how long RNA can survive. He also says it is unlikely that useful information will be obtained from other mammoths, since specimens like Yuka are so rare.

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