World’s oldest RNA extracted only from mammoth

Researchers at Stockholm University – for the first time – have managed to successfully isolate and sequence RNA molecules from Ice Age-only mammoths. This RNA sequence is the oldest known and comes from mammoth tissue preserved in Siberian permafrost for about 40,000 years.

The study, published in the journal Cellit shows that not only DNA and proteins, but also RNA can be preserved for very long periods of time, and provides new insights into the biology of species that have long been extinct.

“With RNA, we can obtain direct evidence of which genes are ‘turned on’, providing a glimpse of the last moments of a very old age that walked the Earth during the last ice age. This is information that cannot be obtained from DNA alone,” says Emilio Mermol, lead author of the study and previously a postdoctoral researcher at Stockholm University.

He now resides at the Globe Institute in Copenhagen. During his time at Stockholm University, he worked with researchers at the Scalf Lab and the Center for Paleogenetics, a joint initiative between Stockholm University and the Swedish Museum of Natural History.

Sequencing prehistoric genes and studying how they are activated is essential to understanding the biology and evolution of extinct species. For years, scientists have been decoding large volumes of DNA to piece together their genomes and evolutionary history.

Still, RNA, the molecule that shows which genes are active, has so far been out of reach. The long-held belief that RNA is too fragile to survive hours after death may have discouraged researchers from looking for these information-rich molecules in mammoths and other long-lived species.

“We had access to exceptionally well-preserved mammoth tissues from Siberian permafrost, which we hoped would contain RNA molecules frozen in time,” Murmol added.

“We’ve previously pushed the limits of DNA recovery over a million years,” says Leo Dillon, professor of evolutionary genomics and the Center for Paleogenetics at Stockholm University.

The oldest RNA ever sequenced

The researchers were able to identify tissue-specific patterns of gene expression in frozen muscle from the remains of Yuka, a juvenile who died about 40,000 years ago. Of the more than 20,000 protein-coding genes in the mammoth genome, far from all of them were active. RNAs detected code for proteins with key functions in muscle contraction and metabolic regulation under stress.

“We found signs of cell stress, which is perhaps not surprising because previous research suggested that Yuka had been attacked by cave lions shortly before her death.”

The researchers also found a myriad of RNA molecules that regulate gene activity in large muscle samples.

“RNAs that don’t code for proteins, such as microRNAs, were among the most interesting results we got,” says Mark Friedlander, associate professor in the Department of Molecular Biosciences at Stockholm University and the Wiener Green Institute in Skäfelib.

“Direct evidence for real-time gene regulation in antiquity,” muscle-specific microRNAs are direct evidence for gene regulation in antiquity. This is the first time that something like this has been achieved. “

The microRNAs that were identified also helped the researchers confirm that the findings did indeed come from mammoths.

“We found rare mutations in some microRNAs that provided a smoking gun demonstration of their large lineage. We even detected novel genes based entirely on RNA evidence, which had never before been attempted in such ancient remains,” noted Bastian Fromm, associate professor at the Arctic University Museum (UIT) in Norway.

‘RNA molecules can live much longer than previously thought.

“Our results show that RNA molecules can live much longer than previously thought. This means that not only will we be able to study which genes are ‘turned on’ in different extinct animals, but it will also be possible that RNA viruses, such as influenza and coronaviruses, are conserved in the Ice Age,” he said.

In the future, researchers hope to conduct studies that link prehistoric RNA to DNA, proteins and other conserved biomolecules.

“Such studies can fundamentally reshape our understanding of extinct megafauna as well as other species, revealing many hidden layers of biology that have remained frozen in time until now.”