"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," said Emilio Marmol, lead author of the study.
The research team worked with SciLifeLab and the Centre for Palaeogenetics, a collaboration between Stockholm University and the Swedish Museum of Natural History. They sequenced prehistoric genes to analyze activation patterns crucial for understanding extinct species' biology and evolution. While DNA studies have previously reconstructed mammoth genomes, the unstable nature of RNA made recovery from ancient remains difficult.
"We gained access to exceptionally well-preserved mammoth tissues unearthed from the Siberian permafrost, which we hoped would still contain RNA molecules frozen in time," Marmol explained.
Love Dalen, professor of Evolutionary Genomics at Stockholm University, stated, "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."
The team identified patterns of gene expression specific to muscle tissue taken from Yuka, a juvenile mammoth that died close to 40,000 years ago. Detected RNA molecules were linked to protein regulation involved in muscle contraction and adverse conditions.
"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," Marmol stated.
Researchers discovered numerous RNA molecules regulating gene activity, including microRNAs. "RNAs that do not encode for proteins, such as microRNAs, were among the most exciting findings we got," Marc Friedlander said. "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," he added.
The microRNAs confirmed the mammoth origin through rare mutations and assisted in novel gene identification using only RNA evidence from ancient remains. "We found rare mutations in certain microRNAs that provided a smoking-gun demonstration of their mammoth origin. We even detected novel genes solely based on RNA evidence, something never before attempted in such ancient remains," noted Bastian Fromm.
Love Dalen said, "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."
The researchers plan future studies combining prehistoric RNA, DNA, proteins, and other preserved biomolecules. "Such studies could fundamentally reshape our understanding of extinct megafauna as well as other species, revealing the many hidden layers of biology that have remained frozen in time until now," Marmol said.
Research Report:Ancient RNA expression profiles from the extinct woolly mammoth
Related Links
Stockholm University
Beyond the Ice Age
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