Scientists have recovered the oldest-known RNA, a molecule necessary for most biological functions, from a woolly mammoth that inhabited Siberia about 39,000 years ago, showing it can last longer than previously known and promising a new path for studying organisms that lived long ago.
The RNA, successfully isolated and sequenced, was extracted from muscle tissue in the left front leg of a juvenile male mammoth, perhaps five to 10 years old, whose carcass was discovered in 2010 in the Siberian permafrost in the Russian Far East along the Oyogos Yar coast bordering the Laptev Sea.
The mammoth, given the name Yuka, represents one of the best-preserved frozen carcasses of this extinct species. Its RNA, among other things, revealed which genes had been “turned on” in Yuka’s tissue around the time of death, showing signs of cell stress.
Most knowledge about prehistoric organisms comes from studying skeletal fossils, but there is a limit to what these can reveal about their biology. The growing ability to recover telltale biomolecules from ancient remains, however, has offered new ways to understand such organisms.
The new RNA achievement complements advances in recent years in the study of ancient DNA, the molecule that carries the genetic instructions for all living organisms, and ancient proteins, the molecules that build and run much of a cell’s machinery.
RNA, short for ribonucleic acid, serves as the messages sent from an organism’s genome to its cellular machinery, telling cells which genes to activate or deactivate, how and when to regulate their function and which proteins to make.
“With RNA, you can access the actual biology of the cell or tissue happening in real time within the last moments of life of the organism,” said Emilio Mrmol, a geneticist, veterinarian and bioinformatician at the University of Copenhagen’s Globe Institute, lead author of the study published on Friday in the journal Cell.
“This gives us direct access to the functional landscape of the cell metabolism of woolly mammoths when they were alive, something that is not possible, at least not in the lengths we report, just by using DNA or proteins. Adding this layer of information provides a more comprehensive view to the biology of woolly mammoths,” Mrmol said.
RNA is more fragile than DNA and proteins. The oldest DNA recovered to date was from animals, plants and microbes dating to about 2 million years ago from sediment in Greenland. The oldest proteins came from dental remains of a hornless rhinoceros that lived about 23 million years ago in the Canadian High Arctic.
Until now, the oldest RNA recovered was from a wolf cub that lived in Siberia about 14,000 years ago.
“I think the key finding is that we can recover RNA from such an old sample. It’s a proof of principle that opens the door for much more detailed analyses of gene expression patterns in Ice Age megafauna,” said geneticist and study co-author Love Daln of Stockholm University and the Centre for Palaeogenetics in Sweden.
Yuka experienced trauma before death, with deep cuts on its hide indicating an attack by a cave lion, an extinct species that was a cold-adapted and bulkier cousin of today’s African lion.
“None of the marks are severe enough to have caused the death, so it is still a bit unclear why Yuka died,” Daln said.
The researchers detected RNA molecules in Yuka that code for proteins involved in muscle contraction and metabolic regulation under stress, possibly but not necessarily stemming from this attack.
Scientists long thought RNA degrades mere minutes or hours after death, but this study and others showed that under the right circumstances, it can survive much longer. The frigid conditions of Siberia were particularly conducive to RNA preservation.
Yuka’s DNA has also been sequenced by these researchers and others previously. Previously thought to have been female, the genetic data showed that Yuka, which stood about 5-1/4 feet (1.6 meters) at the shoulder, was male, with an X and a Y chromosome.
The researchers believe that under the right conditions, RNA can be recovered from even older remains, noting that ancient RNA offers numerous possibilities.
“We hope our work elicits a renewed interest in exploring RNA in other old remains, not necessarily from the Ice Age or extinct species, but also from medieval or historical remains of both extinct and extant organisms,” Mrmol said.
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