The extraction and sequencing of ancient DNA has revolutionized scientists’ understanding of many extinct species, but DNA can only tell us so much. However, RNA can tell us which genes were actually “on”, providing unprecedented insight into the final moments of a dead animal’s life. Amazingly, the recent recovery of ancient giant RNA does just that.
The long-held belief that RNA is too fragile to survive even a few hours after death has discouraged experts from looking for it in preserved mammoths and other ancient species, but new research has debunked that notion. In the study published Friday in the journal Cell, researchers successfully isolated and sequenced RNA molecules from Ice Age woolly mammoths for the first time.
These RNA sequences are the oldest ever recovered, extracted from mammoth tissues preserved in Siberian permafrost for approximately 40,000 years. This suggests that RNA can remain viable in dead tissue for much longer periods of time than previously thought. Additionally, the analysis revealed previously inaccessible details about woolly mammoth biology and what was happening in the moments before the animals died.
“With DNA alone, you may at most be able to predict whether a gene was active or inactive based on how tightly or loosely packed the DNA is,” study lead author Emilio Marmol, a postdoc at the Globe Institute at the University of Copenhagen, told Gizmodo in an email. “But with RNA you can access direct evidence of this expression in the form of RNA transcripts present in the cell.”
The mystery of the death of Yuka, a young mammoth
Marmol and colleagues extracted RNA sequences from the muscles and skin of 10 permafrozen woolly mammoth specimens found in northeastern Siberia. Analysis of one sample, a juvenile mammoth named Yuka, revealed RNA molecules that code for proteins that play important roles in muscle contraction and metabolic regulation under stress.
“We found some protein-coding and microRNA signals of cell stress that may be caused by the cell dying (ie, we actually got the last glimpse of gene expression just before the cell died) or as a precursor to muscle stress,” Marmol explained.
“This may be a reflection of Yuka’s avoidance of predators, perhaps cave lions, given the signals present in her body, but it is not really possible to accurately understand whether the stress markers are due to avoidance of predators or due to cells dying based on our data,” he explained.
The researchers also found muscle-specific microRNAs that are essential for muscle metabolism, providing direct evidence of gene regulation occurring in real time in an ancient animal. Furthermore, microRNA analysis helped confirm that the findings did indeed come from ancient mammoths.
One particularly important microRNA (mir-1) has a rare mutation in most of its sequences that is usually found only in elephants and their close relatives, although it may also appear in some other animals such as redworms and lampreys, according to Marmol.
“However, since we found no evidence of additional contamination from these species other than mammoths, we believe that these miR-1 sequences harbor such [a] rare mutation [are] There is shotgun evidence that they are genuine ancient RNA molecules,” he said.
a treasure trove of new opportunities
The findings have opened up a whole new world of ancient genomic research. Marmol said, “We hope that our work will spark interest in exploring RNA in other ancient remains, not only from Ice Age or extinct species, but also from medieval or historical remains of both extinct and extant organisms.”
He noted that future studies could examine combined DNA, RNA, and protein analysis to provide a more complete picture of the biology of ancient species. This can be useful not only for understanding complex organisms but also for understanding simple life forms such as RNA viruses.
“Many past pandemics that we still don’t know about may have originated from RNA viruses,” Marmol said. Gaining a more robust understanding of past RNA viruses will not only clarify their evolution, he said, but will also help us predict and respond to future pandemics.