While we probably won’t see hormone-fueled, giant woolly mammoths stomping around the Earth any time soon, we know significantly more about this extinct mammal’s genome. An international team of scientists have discovered ancient chromosomes on the preserved skin of a woolly mammoth. This animal died about 52,000 years ago and the fossils preserved the structure of these ancient building blocks of life on the nanometer scale–or down to the billionths of a meter. The discovery is detailed in a study published July 11 in the journal Cell and shows how chromosomes can help scientists reassemble the genomes of extinct species.
“We’ve known that tiny fragments of ancient DNA can survive for long periods of time,” study co-author and Center for Evolutionary Hologenomics at the University of Copenhagen paleogenomicist Marcela Sandoval-Velasco said in a statement. “But what we found here is a sample where the three-dimensional arrangement of these DNA fragments was frozen in place for tens of millennia, thereby preserving the structure of the whole chromosome.”
52,000-year-old genetic material
Fossil chromosomes like these offer scientists new ways to study the history of life on our planet. Typically, ancient DNA fragments aren’t longer than 100 base pairs, or 100 letters of genetic code. The full DNA sequence of an elephant–a relative of the woolly mammoth–is usually about 3.2 billion base pairs and are billions of letters long. These more commonly found DNA fragments are just a tiny glimpse into their genetic code. However, fossil chromosomes can span hundreds of millions of genetic letters.
[Related: This is the most-complete woolly mammoth ever found in North America.]
“By comparing ancient DNA molecules to the DNA sequences of modern species, it’s possible to find cases where single letters of the genetic code have changed,” study co-author and Baylor College of Medicine genomicist Olga Dudchenko said in a statement. “Fossil chromosomes are a game-changer, because knowing the shape of an organism’s chromosomes makes it possible to assemble the entire DNA sequence of extinct creatures. This enables the types of insights that would not have been possible before.”
Since these fossil chromosomes came from a woolly mammoth, one of the first steps was to try and determine the number of chromosomes that this animal had when it was living.
“We found that they had 28 pairs of chromosomes, which makes a lot of sense, because that’s what modern elephants have, and they are the woolly mammoth’s closest living relative,” Juan Antonio Rodríguez, a study co-author and genomicist at University of Copenhagen and at Centre Nacional d’Anàlisi Genòmica in Barcelona, said in a statement. “It was extremely exciting to be able to count the chromosomes of an extinct creature for the first time. It’s usually not possible to have this much fun simply counting from one to 28.”
Big mammal, tiny particles
The team extracted the fossil chromosomes from the skin of a mammoth uncovered in 2018. With it, they could see which genes were active through a phenomenon called chromosome compartmentalization. This is where active and inactive DNA tend to split off into two spatial areas within the cell nucleus. For most of the mammoth’s genes, the activity state matches what researcher’s saw in modern elephants. However, this was not always the case.
“The fact that the compartmentalization was still preserved in these fossils was critical, because it made it possible to look, for the very first time, at which genes were active in a woolly mammoth,” Thomas Gilbert, a study co-author and director of the Center for Evolutionary Hologenomics, said in a statement. “And it turns out that there are key genes that regulate hair follicle development whose activity pattern is totally different than in elephants.”
When they looked inside the chromosomes, the team observed more than just compartmentalization. The chromosomes shared several structural features with modern chromosomes. The most striking common feature happened to be the smallest–chromatin loops. These structures are as small as 50 nanometers, or roughly the size of a virus.
“The survival of loops in these ancient chromosomes is perhaps the most impressive part,” Marc A. Marti-Renom, study co-author and genomicist at Spain’s Centre for Genomic Regulation, said in a statement. “DNA loops, which are only 50 nanometers in size, are important because they bring activating DNA sequences close to their gene targets. So, these fossils don’t just show us which genes were active–they show us why.”
Freeze-dried woolly mammoth ‘jerky’
However, a puzzle still remained. How was it possible that DNA fragments of ancient chromosomes survived for over 50,000 years with their three-dimensional structure intact? The team found that the chromosome fossils looked similar to the state of molecules in glass–a special state called chromoglass.
“Chromoglass is a lot like the glass in your window: it’s rigid, but it’s not an ordered crystal,” study co-author and director of the Center for Genome Architecture and Baylor College of Medicine professor Erez Lieberman Aiden said in a statement. “If you zoom in on the individual particles, a piece of glass–or a piece of chromoglass–is basically a bumper-to-bumper nano-scale traffic jam, in a world with no lane markers. Individual particles, or individual fragments of ancient DNA, just can’t move very far in that situation. Even if you wait for thousands and thousands of years.”
[Related: Scientists made a woolly mammoth meatball, but don’t grab your fork yet.]
Over time, many civilizations developed ways to induce a “glass transition” in their food to preserve it. It usually is through a mixture of cooling and dehydration that results in foods like beef jerky. They are more brittle than the original food, but can last longer. The researchers discovered that the chromosome fossils had essentially been trapped inside a piece of freeze-dried woolly mammoth jerky.
“We confirmed this theory by doing experiments on old, freeze-dried beef jerky, which is much easier to find than woolly mammoth jerky,” study co-author and Baylor genomicist Cynthia Pérez Estrada aid in a statement. “We fired a shotgun at it. We ran over it with a car. We had a former starting pitcher for the Houston Astros throw a fastball at it. Each time, the jerky broke into tiny bits–shattering like a glass. But at the nano-scale, the chromosomes were intact, unchanged. That’s the reason these fossils can survive. That’s the reason that they were there, 52,000 years later, just waiting for us to find them.”
