Stockholm University Scientists Extract World's Oldest RNA from 40,000-Year-Old Woolly Mammoth

Credit: Valeri Plotnikov

Researchers from Stockholm University have made a groundbreaking discovery, successfully extracting and sequencing the world's oldest RNA molecules from a woolly mammoth that died approximately 40,000 years ago.

This unprecedented achievement, published in the journal Cell, reveals which genes were active in the Ice Age giant's final moments and opens a new window into the biology of extinct species.

The study, led by former Stockholm University postdoctoral researcher Emilio Mármol, focused on exceptionally preserved muscle tissue from a juvenile mammoth named Yuka, found in the Siberian permafrost.

While scientists have long studied ancient DNA to reconstruct genomes, RNA has remained elusive because it was considered too fragile to survive. RNA is crucial because it shows which genes were actively "turned on," providing a real-time snapshot of biological activity that DNA alone cannot offer.

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“With RNA, we can obtain direct evidence of which genes are ‘turned on’, offering a glimpse into the final moments of life of a mammoth that walked the Earth during the last Ice Age. This is information that cannot be obtained from DNA alone,” says Emilio Mármol, the study's lead author.

The international team included scientists from SciLifeLab and the Centre for Palaeogenetics, a collaboration between Stockholm University and the Swedish Museum of Natural History.

The research team identified tissue-specific gene expression in the ancient muscle, analyzing over 20,000 protein-coding genes. They found active RNA molecules related to muscle contraction and metabolic regulation under stress.

Intriguingly, the data revealed signs of cell stress, which aligns with previous evidence suggesting Yuka was attacked by cave lions shortly before death, reported the research team in their publication.

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One of the most exciting aspects of the discovery was the detection of non-coding RNA molecules, such as microRNAs, which regulate gene activity. “The muscle-specific microRNAs we found in mammoth tissues are direct evidence of gene regulation happening in real time in ancient times.

It is the first time something like this has been achieved,” says Marc Friedländer, associate professor at the Department of Molecular Biosciences at Stockholm University. These microRNAs also contained rare mutations that definitively confirmed their origin was from a mammoth and not modern contamination.

“We have previously pushed the limits of DNA recovery past a million years. Now, we wanted to explore whether we could expand RNA sequencing further back in time than done in previous studies,” says Love Dalén, professor of Evolutionary Genomics at Stockholm University.

The success demonstrates that RNA can survive for tens of thousands of years in frozen conditions, shattering the long-held belief that the molecule degrades rapidly after death.

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This breakthrough has profound implications for paleogenetics. “Our results demonstrate that RNA molecules can survive much longer than previously thought. This means that we will not only be able to study which genes are ‘turned on’ in different extinct animals, but it will also be possible to sequence RNA viruses, such as influenza and coronaviruses, preserved in Ice Age remains,” notes Professor Love Dalén. The team now aims to combine prehistoric RNA data with DNA and protein studies to build an even more comprehensive picture of extinct life.