Oldest sequenced RNA reveals details about a mammoth’s final moments 40,000 years

Scientists have recovered ancient RNA molecules from a juvenile mammoth named Yuka, who died 40,000 years ago in what is now Siberia. These biological remains provide insight into the final moments of the life of this extinct Ice Age creature.

The RNA was extracted from extremely well-preserved mummified leg tissue for millennia in permafrost. It is the oldest RNA sequenced by scientists. Today, researchers are using it to reveal which mammoth genes were active at the time of its death.

“All cells in an organism have the same DNA, a brain cell, a liver cell or a muscle cell. What differentiates these cells from each other is essentially RNA,” said Love Dalén, professor of evolutionary genomics at the Center for Paleogenetics at Stockholm University and the Swedish Museum of Natural History and lead author of the study published Friday in the scientific journal Cell. “It’s about how genes are turned on and off in different cell types.”

DNA and RNA are found in all living things. DNA is the hard code of life, while RNA reads these genetic instructions and acts as a messenger to help a cell build proteins.

Ancient DNA can last for more than a million years and has revolutionized scientists’ understanding of the past.

However, until recently, RNA was thought to be ephemeral, and it is not yet clear whether the researchers’ new techniques will work on specimens that are not as exceptionally preserved.

During the research, the team studied 10 frozen mammoth tissue samples, including muscle and skin, with three RNA fragments.

Of these, only one produced detailed sequencing data that could reveal how the animal’s genes might have been functioning at the time of its death, the team said. This sample belonged to Yuka, whose body was found in 2010 in Oyogos Yar in northeastern Siberia.

In the data, the researchers were able to detect messenger RNA molecules, which code for proteins, as well as microRNAs, which regulate gene activity. Together, they revealed some of “the biology that was happening in the cells of this mammoth just before it died,” said Emilio Mármol Sánchez, the study’s lead author and a postdoctoral researcher at the Globe Institute at the University of Copenhagen in Denmark.

“We hypothesize that this animal was about to die, and this manifests itself in muscle metabolism,” said Mármol Sánchez.

The data suggests a “predominance of slow-twitch muscle fibers in the mammoth tissue,” the study notes, adding that the signature may have been the tissue’s “final impulses.” For example, one of the active proteins was titin, linked to muscle elasticity, and another was nebulin, involved in skeletal muscle contraction.

“The muscle-specific microRNAs we found in mammoth tissues are direct evidence of gene regulation occurring in real time in ancient times,” Marc Friedländer, study co-author and associate professor in the department of molecular biosciences at the Wenner-Gren Institute at Stockholm University, said in a statement. “This is the first time something like this has been done.”

It makes biological sense that the mammoth’s muscle would have been active at the time of its death, said Erez Lieberman Aiden, a professor of biochemistry and molecular biology at the University of Texas Medical Branch, who was not involved in the research.

“You don’t want the first study like this to uncover a completely shocking pattern,” Aiden said. “The idea that you can detect tissue-specific expression is pretty impressive.”

Dalén, who sequenced the world’s oldest mammoth DNA, said the techniques developed by the team had the potential to open a new avenue of scientific research in the past.

“These 10 samples are all really good and unique, and only the best three worked, so at first glance it seems pretty niche,” he explained. “My hunch is that the methods will improve. There are many laboratories around the world excited about RNA, and I’m sure we will develop much better methods for recovering RNA.”

This approach, if it can be applied more widely, will offer a way to study the evolution of ancient viruses, many of which only exist as RNA, like the virus that causes Covid-19, Dalén said. By sequencing the DNA of ancient bacteria, scientists have been able to study the genetic origins and evolution of disease-causing bacteria such as plague and syphilis.

This approach could also be applied to efforts to bring back extinct animals in some form, said Dalén, scientific adviser to the Texas-based biotechnology company Colossal Biosciences, which aims to “resurrect” the mammoth, the dodo and the Tasmanian tiger, among others, by editing the genomes of their closest living relatives. This would result in hybrid animals that are visually indistinguishable from extinct species.

“In principle, the methods used here could be a tool that could help Colossal and others narrow down which genes to edit,” he said.

Although mammoth RNA is the oldest that scientists have discovered to date, it is not the first. In 2023, Mármol Sánchez led a study sequencing the RNA of a 130-year-old Tasmanian tiger, or thylacine, at the Swedish Museum of Natural History in Stockholm.

And in 2019, a team sequenced RNA from 14,300-year-old wolf skin preserved in permafrost. Scientists also detected RNA in the tissues of Ötzi the Iceman, a 5,300-year-old mummy found frozen in the Alps.

Aiden, who has studied mammoth remains, said the paper was a “significant step forward”, but it was not yet clear whether it would represent a turning point in the field – or whether RNA would become, like DNA, a major reservoir of information about an extinct organism.

It’s like being invited to a wedding and being asked how happy the marriage would be, he added.

“These moments are a little hard to judge,” Aiden said.

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