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Frozen in Siberia, this mammoth was remarkably preserved at the microscopic level, Northeastern researchers discovered. Its DNA had remained the same for thousands of years, frozen as “chromoglass.”
The 52,000-year-old freeze-dried remains of a woolly mammoth were so remarkably preserved that scientists were recently able to reconstruct its genome. Their discovery not only unearths new information about these ancient creatures but reveals a new kind of natural preservation that could open the door to studying other intact ancient animals.
“This is fascinating because this is a new type of fossil,” says Michele Di Pierro, an assistant professor of physics at Northeastern University who was one of many researchers involved in the research that was published in Cell. “Typically, we see in fossils the displacement of organic material with minerals, and that preserves larger structures. Here, this is a molecular fossil. Here we’re talking about each piece of DNA … is in exactly the same position as it was 50,000 years ago.”
Di Pierro, who also serves as scientific lead for the Center for Theoretical Biological Physics, and Bernardo Zuillaga Herrera, a postdoctoral researcher at Northeastern, joined the massive research effort to answer one question.
In most DNA samples that are this old, the tiny pieces of DNA that make up an animal’s chromosomes are so degraded and fractured that it’s difficult to reconstruct the genome at all, let alone its three-dimensional architecture. So, how is it possible that the genetic structure of a woolly mammoth remained intact for tens of thousands of years?
Zuillaga Herrera had already been studying the use of computational tools and simulations to model experiments based on Hi-C, the genomic analysis technique being used in this study. Using those models, Zuillaga Herrera and Di Pierro determined the secret behind the mammoth’s remarkable preservation.
“It seems to be the case that the very, very dry and cold conditions of the Siberian permafrost help a heck of a bit because it helped the material of the nucleus of the cell enter into a so-called glassy state where these tiny fragments of DNA have completely arrested motion,” Zuillaga Herrera says.
This so-called glass transition is the same process responsible for the extended shelf life of certain food products. In the case of the woolly mammoth sample, the researchers have termed this state chromoglass. Their theoretical predictions suggest that DNA preserved as chromoglass could survive indefinitely, certainly for much longer than anyone could previously guess.
The researchers re-created this process by freeze-drying liver and meat samples from a variety of animals and testing the durability of the genome 3D architecture in some creative ways, Zuillaga Herrera says. They rode over the samples with a car, shot them with a shotgun and even had a former Houston Astros pitcher hit them with a fastball. Through all those tests, the sample was certainly damaged at a macroscopic level, but at the microscopic level, the three-dimensional genetic structure remained perfectly preserved.
With such a well-preserved fossil to work from, the researchers were able to use a variation of Hi-C, a technique that involves using chemical reactions to reveal the three-dimensional structure of genetic material. The method the researchers invented, known as Paleo Hi-C, achieves the same result with often-fragmented ancient samples by using the DNA of a close genetic relative to help fill in the gaps. In this case, they used the modern elephant.
By using this kind of 3D sequencing technique, the researchers not only reconstructed the mammoth’s genome, they counted the number of chromosomes in a mammoth for the first time. It turns out mammoths and elephants have the same number of chromosomes: 28 pairs.
“If this DNA is a long book that tells a story, the story of the elephant is not very different than the story of the mammoth,” Di Pierro says. “Even though the words might be a bit different, you can still reliably align it to the genome of the elephant.”
However, the researchers could read the genetic structure of the mammoth in new ways that actually allowed them to see which genes were active in the mammoth and, by comparison, which aren’t active in elephants. The most important and obvious difference Di Pierro says is that the genes related to hair growth and cold weather adaptation “are indeed more active in the mammoth.”
Zuillaga Herrera says the hope is that the Paleo Hi-C method and the discovery of this natural freeze-drying method could extend to other kinds of samples, even those in hot, dry conditions, like Egyptian mummies.
“It opens up the possibility that there are ancient samples of other animals or other ancient organisms that have also entered into this glassy state after something like freeze-drying,” Zuillaga Herrera says. “If the experiment was successful on the mammoth, then perhaps this opens up the possibility of carrying out the same experiment on other kinds of ancient animals.”