Sign up for CNN’s Wonder Theory science newsletter. Explore the universe with news about fascinating discoveries, scientific advances, and more.
Fossil chromosomes have been found in a piece of woolly mammoth skin unearthed from the permafrost in Siberia, the first of its kind, according to new research.
Researchers unearthed the 52,000-year-old remains in 2018 near the village of Belaya Gora in northeastern Siberia, where freezing temperatures helped preserve in detail the structure of chromosomes, the tiny threadlike structures that carry genetic material, or DNA.
While ancient DNA samples have been found many times before, they are usually quite fragmented and contain only hundreds of letters of genetic code. Fossil chromosomes contain millions and provide a much more complete picture of an animal’s genetic code.
“Fossil chromosomes have never been found before,” said Erez Lieberman Aiden, professor of molecular and human genetics at Baylor College of Medicine and co-author of the study published Thursday in the journal Cell.
Lieberman Aiden added that in previous findings the fragments also lacked an orderly structure. “Here the fragments are clearly arranged in 3D – essentially the same as in the original chromosomes in the living mammoth.”
The chromosomes, which the researchers describe as “unmineralized fossils or subfossils,” are in a state of preservation good enough to constitute the genome, or the sum of all genetic material, of an extinct species, according to Olga Dudchenko, co-first author of the study and an assistant professor of molecular and human genetics at Baylor College of Medicine.
“We believe this will not just apply to the mammoth or to any particular mammoth,” said Dudchenko, a senior researcher at Rice University’s Center for Theoretical Biological Physics. “In fact, this opens up a new area with tremendous potential.”
DNA diffusion
DNA in different cell types is organized into distinct, specific 3D structures that provide insight into particular characteristics or attributes of that cell type, said Kevin Campbell, a professor of environmental and evolutionary physiology at the University of Manitoba in Canada, who was not involved in the study.
After death, body cells degrade rapidly and this 3D structure is lost in a few days or less, he added. In Arctic animals such as the woolly mammoth, the degradation is slower due to freezing temperatures, but the DNA is still damaged and is expected to lose the structure and qualities that make up the biology of the species over long periods of time.
“But this study is the first to show that this is not always the case,” Campbell said in an email.
“DNA is a very, very long molecule, and when it sits there after an animal dies, it starts to degrade and breaks into shorter pieces,” Dudchenko said.
“Normally what you would expect is for all of these pieces to start shifting relative to each other and kind of drift away, losing all of the organization that was there,” Dudchenko said. “But clearly, in this particular example, that didn’t happen.”
This loss of structure is called diffusion, and food scientists know how to prevent it. It’s not too different from making pastrami from beef, he added.
“Stopping spreading is key to preserving food, so if you want something that has a long shelf life, you basically need a combination of drying and refrigeration,” he said. “Any food that has a shelf life that hasn’t been canned is probably in a state of stopping spreading.”
When the mammoth from which the skin sample was taken died, conditions could have been just right for this process to start naturally. “(The carcass) could have spontaneously gone through the same procedure that we use commercially all the time now,” Dudchenko said, “removing a significant amount of water, stopping diffusion inside and locking the chromosome fragments in place, allowing us to read them 52,000 years later.”
But despite its good preservation, the DNA was not completely intact. “Each chromosome, which was originally one DNA molecule, has fragmented into millions of DNA molecules,” Aiden said in an email. “But the molecules didn’t move much outside of that, not even at the nanometer scale, so we call this a fossil chromosome.”
If this sample had been a book, the binding would have been lost, leaving a large number of unbound pages or DNA fragments, Lieberman Aiden said. The spread is like the wind blowing the pages around, making it impossible to put them back in order. But in this case, the pages never flew away; they remained in a neat stack, just as they were before the binding was lost.
Pulling bacon from beef
The researchers confirmed this theory of protection by doing some experiments on beef jerky to see how badly they could treat the meat snack before the chromosomes lost their structure.
“We decided to test how well this beautiful molecule could withstand stress and damage by having a pitcher from the Houston Astros throw it a fastball and then shoot it with a shotgun,” said Dr. Cynthia Pérez Estrada, co-first author of the study and a researcher at the Baylor Center for Genome Architecture and the Rice Center for Theoretical Biological Physics.
“The beef was breaking down more and more, but the DNA structure was still there, and that showed us that DNA is extremely resilient, especially in this glass-like state (like in the sample), where the molecules are basically frozen and behave like crystals,” Pérez Estrada added.
Thanks to new genetic information found in skin samples, researchers were able to determine for the first time that the woolly mammoth had 28 pairs of chromosomes, just like modern elephants.
But the structure allowed them to go a step further and see which individual genes were active in the animal. “Everyone wants to know exactly what makes it woolly,” Dudchenko said, “and we have some ideas because of the way these chromosomes are preserved.”
Mammoth dreams
The researchers were able to compare individual genes in the mammoth sample with equivalent genes in modern elephants and noticed differences in the activity of genes that regulate hair follicles. However, DNA from elephants was also needed to piece together the mammoth genome.
“Our dream and hope was to assemble the entire mammoth genome, but we’re not quite there yet — we still used some information from its closest relatives to help, because the amount of data we were able to get from the mammoth was lower than what you would normally need,” Dudchenko said. “But the fundamentals tell us that we can do this (without the help of elephant DNA) as we continue to work in this direction.”
Could fossil chromosomes make the dream of resurrecting the woolly mammoth a reality? “The basic biology that we learn from this is going to be useful, no doubt about that,” Dudchenko said. “Are we any closer? We’re a step closer, but we still have a few steps ahead of us, and there are all sorts of other considerations that are beyond basic science.”
The researchers also hope that the same methodology used in the mammoth sample can be applied to samples from other species.
“We hope to find chromosome structures in museum specimens,” said Marcela Sandoval-Velasco, a visiting researcher at the Center for Evolutionary Hologenomics at the University of Copenhagen in Denmark and co-first author of the study. “Not just permafrost samples, because that narrows it down a lot, but also samples from museum collections. There’s tremendous potential there,” she added, citing the woolly rhinoceros, extinct lions and passenger pigeon as some of the extinct species that scientists could learn more about in this way.
According to Pérez Estrada, this potential opens the door to further exploration.
“It’s going to take a tremendous effort to find suitable samples, so there’s a lot of work ahead of us – but I wouldn’t be surprised if we then discover something completely new and different from what we have now,” he said. “That’s also a really exciting open question: What else and what other physical properties (of DNA) might be preserved?”
Exciting findings
Researchers not involved in the study also expressed excitement about the findings.
Peter Heintzman, a paleogeneticist at Stockholm University in Sweden, said the study is the first to reconstruct the structure, or architecture, of the genome of an extinct species that lived during the last ice age. “This structural information provides insights into functions of the woolly mammoth genome that were not visible using previous genomic methods,” Heintzman said in an email. “This advance therefore helps unlock a new and exciting frontier in paleogenomics, the study of ancient genomes, and will likely provide greater insight into how extinct species evolved, survived, and went extinct.”
Dmitry Filatov, a professor of biology at the University of Oxford in England, said the high-quality, chromosome-level reconstruction of the mammoth genome reported in this study was surprising because of how significantly degraded and fragmented DNA recovered from ancient samples often is.
“It is even more surprising that the researchers managed to infer which genes were on and which were off in the mammoth sample and compare this with gene expression in elephants,” Filatov said in an email. “This will certainly stimulate further paleo-genomic research in other species.”
Hendrik Poinar, director of the Ancient DNA Centre at McMaster University in Ontario, called the paper “very exciting.” Poinar said researchers normally can’t do anything remotely resembling assembling a genome with fossil remains.
“I don’t know how many tissue samples will be preserved at this level,” he added in an email, “but I think this method will allow us to think of new ways to extract DNA from tissues in ways other than what we’re used to.”
For more CNN news and bulletins, create an account at CNN.com