Discovery of ‘dried’ mammoth in Siberia is a giant step towards its ‘resurrection’

It’s been 4,000 years, but they’re almost there. Back. Some point in the Arctic tundra, perhaps an uninhabited Siberian island mimicking Jurassic Park’s Mount Nublar, would be the perfect place to soon resurrect an icon of the Ice Age: the mammoth. Science says it has, of course, just taken a giant step with the accidental discovery of fossilized chromosomes from a woolly mammoth that died a long time ago. 52,000 years in the permafrost of Siberia.

Chromosomes a million times longer than most ancient DNA fragments discovered to date, and provide information about how the mammoth’s genome was organized within its living cells. The unprecedented level of structural detail was achieved because the mammoth was naturally freeze-dried shortly after death. Its DNA was preserved in glass, as the billionaire would have paid for luxurious preservation for the sake of future resurrection.

So far, all the giant cloning projects have faced challenges at every step. First: finding a whole, intact strand of DNA. This is a new discovery, the results of which have just been published in the journal cellwas so well preserved that researchers were able to infer genes linked to the mammoth’s woolliness and cold tolerance for the first time. “This means we are one step closer to assembling the genomes of ancient extinct species, which is important for de-extinction,” says M. Thomas Gilbert, a paleogenomist at the University of Copenhagen and the Norwegian University of Science and Technology, and a signatory to the study.

Once the DNA is recovered, it will have to be fused with the egg of an Asian elephant, the closest living relative of mammoths. shares 99.6% of its genetic code. Then insert it into the womb of the closest-sized female African elephant, and if the process is successful, in 22 months the closest thing to a baby mammoth will be born.

Biotech company Colossal claims we could see a baby mammoth in 2028 after we manage to transform cells from modern Asian elephants into stem cells that can transform into all the different cell types that make up their bodies.

Juan Antonio Rodriguez, a researcher at the National Genomic Analysis Centre in Barcelona, ​​Spain, and the University of Copenhagen, Denmark, is less clear-cut: “My personal conclusion is that we should be focusing resources on not destroying and protecting existing biodiversity, rather than spending millions to revive something very large and complex, we would not know what consequences it would have for the ecosystem and animal welfare. How can a 3D structure necessarily become something necessary, but not the only thing? I think they could create mammophantan elephant with a few mammoth genes here and there, but quite far from a true mammothwhich I don’t know if we’ll see in our lifetime. Also, it would take a lot of individuals to create a stable population over time.”

Fossil chromosomes are a powerful new tool for studying the history of life on Earth because they allow us to piece together the complete DNA sequence of extinct creatures, giving us knowledge that was previously impossible. This is because typical fragments of ancient DNA rarely consist of more than 100 base pairs, or 100 letters of genetic code, much smaller than an organism’s entire DNA sequence, which often consists of billions of letters. Instead, Fossil chromosomes can span hundreds of millions of genetic letters.

The researchers analyzed dozens of samples over five years before discovering this specimen in northeastern Siberia in 2018. “We knew that tiny fragments of ancient DNA could persist for long periods of time. But here we found a specimen in which the three-dimensional arrangement of these DNA fragments had been frozen in place for tens of millennia, thus preserving the structure of the entire chromosome,” said Dr. Marcela Sandoval-Velasco of the University of Copenhagen’s Center for Evolutionary Hologenomics and co-author of the new study.

To reconstruct its genomic architecture, the researchers extracted DNA from skin sample taken from behind the earusing a method called Hi-C. “Imagine you have a jigsaw puzzle with 3 billion pieces, but you don’t have an image of the final puzzle to work with. Hi-C allows you to get a rough idea of ​​that image before you start putting the pieces together,” explains Marc A. Marti-Renom, research professor at ICREA and a specialist in structural genomics at the National Centre for Genomic Analysis (CNAG) and the Centre for Genomic Regulation (CRG) in Barcelona.”

Hi-C analysis was combined with DNA sequencing to identify interacting regions and create a sequenced map of the mammoth genome, using the genome of modern elephants as a template. Analysis showed that woolly mammoths had 28 chromosomes, the same as today’s Asian and African elephants. Amazingly, the mammoth’s fossilized chromosomes also retained a wealth of detail. The researchers were able to identify active and inactive genes within the cells and found that the mammoth’s fur had different patterns of gene activation than its closest relative, the Asian elephant, including those related to its wooliness and cold tolerance. “It was extremely exciting to count the chromosomes of an extinct creature for the first time. You can’t usually get that much satisfaction from just counting from one to 28,” says Juan Antonio Rodriguez.

However, researchers were left with a mystery: how could DNA fragments from ancient chromosomes survive for 52,000 years while maintaining their three-dimensional structure? In 1905, Albert Einstein published a classic paper calculating how quickly tiny particles like DNA fragments tend to move through matter. “Einstein’s paper makes a very simple prediction about fossil chromosomes: Under normal circumstances, they shouldn’t exist, and yet: here they are. This is a mystery of physics!– notes Olga Dudchenko, associate professor of molecular and human genetics at the Center for Genome Architecture at Baylor College of Medicine and principal investigator at the Center for Theoretical Biological Physics at Rice University.

To explain this apparent contradiction, the researchers concluded that the chromosome fossils were in a very special state. very similar to the state of molecules in glasssomething that isn’t so far-fetched. Many civilizations have developed ways to vitrify foods as a way to preserve them through a combination of refrigeration and dehydration. This has resulted in products like beef jerky, which are more fragile than the original product but last much longer. In essence, Researchers have discovered that fossilized chromosomes are trapped inside a piece of freeze-dried woolly mammoth.

“We confirmed this theory by conducting experiments with old freeze-dried beef jerky, which is much easier to find than woolly mammoth jerky,” explained Dr. Cynthia Perez Estrada, a co-author of the study and a research scientist at Rice University’s Center for Genomics Architecture and the Center for Theoretical Biological Physics.We shot him with a shotgun, we ran him over with a car. and each time the jerky shattered into tiny pieces like glass, but at the nanometer scale the chromosomes remained intact, unaltered. “That’s why these fossils can survive, and why they’re out there 52,000 years later, waiting for us to find them.”

While the method used in this study relies on exceptionally well-preserved fossils, the researchers hope it can also be used to study other ancient DNA samples, including Egyptian mummies.

“Museum mummies, if they are well preserved, could give us information about the gene activation profiles that were occurring at the time of death, allowing us, for example, to understand the environmental conditions,” explains Juan Antonio Rodríguez. “If we are talking about mummies of something other than humans, such as animal collections in museum basements, again, if the tissue samples have undergone the vitreous transition that we are talking about, it would allow us to study and use these samples to create, for example, reference genomes of extinct species or to use the information for the conservation of species.”