Scientists sequence oldest RNA from 40,000-year-old mammoth

Researchers at Stockholm University have isolated and sequenced the oldest RNA ever recovered, from a woolly mammoth preserved in Siberian permafrost for nearly 40,000 years. This breakthrough reveals active genes in the mammoth's tissues, providing insights into its biology and final moments. The findings, published in Cell, demonstrate RNA's surprising longevity and open new avenues for studying extinct species.

For the first time, scientists have successfully extracted and sequenced RNA from Ice Age woolly mammoths, marking a milestone in paleogenomics. The RNA comes from muscle tissue of Yuka, a juvenile mammoth that died around 40,000 years ago, unearthed from the Siberian permafrost. Led by Emilio Mármol, formerly a postdoctoral researcher at Stockholm University and now at the Globe Institute in Copenhagen, the team collaborated with SciLifeLab and the Centre for Palaeogenetics, a joint initiative between Stockholm University and the Swedish Museum of Natural History.

The study, published in the journal Cell, shows that RNA can persist alongside DNA and proteins for millennia, contrary to earlier assumptions about its fragility. The sequences reveal which genes were active in the mammoth's muscle, coding for proteins involved in muscle contraction and metabolic responses to stress. "We found signs of cell stress, which is perhaps not surprising since previous research suggested that Yuka was attacked by cave lions shortly before his death," says Emilio Mármol.

Among the discoveries were ancient microRNAs, non-coding RNAs that regulate gene activity. These provided direct evidence of real-time gene regulation in the mammoth and confirmed its origin through rare mutations. "RNAs that do not encode for proteins, such as microRNAs, were among the most exciting findings we got," says Marc Friedländer, associate professor at Stockholm University's Department of Molecular Biosciences. Bastian Fromm, associate professor at the Arctic University Museum of Norway, noted that they even detected novel genes based solely on RNA evidence.

"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," Mármol explains. Love Dalén, professor of Evolutionary Genomics at Stockholm University, adds, "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."

Woolly mammoths roamed Eurasia and North America during the last Ice Age, from about 115,000 to 11,500 years ago, adapting to cold climates with thick coats and curved tusks. They disappeared as the climate warmed, with isolated populations surviving until around 4,000 years ago. This RNA work could integrate with DNA and protein studies to deepen understanding of extinct megafauna.

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