Scientists analyze mammoth and find chromosome fossils for the first time

In a new study, a piece of woolly mammoth skin was found containing fossil chromosomes after excavation in a Siberian permafost — which is, roughly speaking, ground frozen for long periods.

Researchers unearthed the remains of a 52,000-year-old mammothin 2018, near the village of Belaya Gorain northeastern Siberia, where freezing temperatures helped preserve the makeup of chromosomes — small filamentous structures that carry genetic material, or DNA — in minute detail.

Although samples of ancient DNA have been found on other occasions, they tend to be highly fragmented and contain only hundreds of letters of genetic code. Fossil chromosomes contain millions, offering a much more complete view of an animal’s genetic code.

“Fossil chromosomes have never been found before,” he said Erez Lieberman Aidenprofessor of molecular and human genetics at Baylor College of Medicine and co-corresponding author of the study published on Thursday (11), in the journal Cell.

In previous discoveries, the fragments also lacked an organized structure, Lieberman Aiden added. “Here, the fragments are clearly organized in 3D — essentially as they were in the original chromosomes in the living mammoth.”

According to Olga Dudchenko, assistant professor of molecular and human genetics at Baylor College of Medicine and co-first author of the study, the chromosomes, referred to as “non-mineralized fossils, or subfossils” by researchers, are in a good state of preservation. enough to assemble the genome — or the sum of all genetic material — of an extinct species.

“We strongly believe that this will not just apply to the mammoth or this specific mammoth,” said Dudchenko, who is also a senior researcher at the Center for Theoretical Biological Physics at Rice University. “But, in practice, it is the beginning of a new area of ​​research with great possibilities,” she added.

DNA diffusion

In different cell types, DNA sits in distinct and specific 3D structures that provide insights into the particular properties or characteristics of that cell type, he said. Kevin Campbellprofessor of environmental and evolutionary physiology at the University of Manitoba, Canada, who was not involved in the study.

After death, the body’s 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, degradation is slower due to freezing temperatures, but DNA still becomes damaged and, over long periods, is expected to lose the structure and attributes that make up the species’ biology. .

“However, this study is the first to demonstrate that this is not always the case,” Campbell said in an email. “DNA is a very long molecule, and after the death of an animal, it begins to deteriorate and divide into smaller fragments,” explained Dudchenko.

“What you normally expect is that all these pieces start to move relative to each other and disperse, losing whatever organization there was,” Dudchenko said. “But clearly, in this particular sample, that didn’t happen.”

This loss of structure is called diffusion, and the way to avoid it is well known to food scientists — and it’s not much different from the production of jerky, he added.

“Avoiding diffusion is key to preserving food, so if you want something that is shelf-stable for a long time, you basically need a combination of dehydration and cooling,” she said. “Any shelf-stable food that is not canned is likely in a state of diffusion blockage.”

When the mammoth in the skin sample died, the conditions may have been exactly right to start this process naturally. “(The carcass) could have spontaneously undergone the same procedure that we use commercially all along,” Dudchenko said, “removing substantial amounts of water, blocking internal diffusion, and fixing these pieces of chromosomes in place, allowing us to read them 52,000 years later.”

But although it was well preserved, the DNA was not completely intact. “Each chromosome, originally one DNA molecule, has fragmented into millions of DNA molecules,” Aiden said in an email. “But the molecules didn’t move much, even at the nanometer scale, which is why we call them fossil chromosomes.”

If this sample were a book, Lieberman Aiden said, the binding would have disappeared, leaving countless loose pages., or DNA fragments. Diffusion is like the wind blowing the pages, making it impossible to put them back in order. But in this sample, the pages were never blown; They remained in a neat pile, exactly as they were before the binding was lost.

Tests on dried meat

The researchers confirmed this preservation theory carrying out some experiments with dried meat to see how badly they could mistreat the food before the chromosomes lost their structure.

“We decided to test how well this beautiful molecule resists stress and damage by asking one of the Houston Astros baseball team’s pitchers to throw a ball and fire a shotgun at it,” said Dr. Cynthia Pérez Estrada, co-first author of the study and researcher at the Baylor Center for Genome Architecture and the Rice Center for Theoretical Biological Physics.

“The jerky was breaking down more and more, but the DNA structure was still there, telling us that DNA is extremely tough and even more so in this kind of glass-like state (like in the sample) where the molecules are basically frozen. and behaving like a crystal,” added Pérez Estrada.

With the new genetic information discovered in the skin samples, researchers determined, for the first time, that the woolly mammoth had 28 pairs of chromosomes, just like modern elephants.

But the structure allowed them to go further and see which individual genes were active in the animal. “Everyone wants to know what exactly made it woolly,” Dudchenko said. “We have some ideas thanks to the way these chromosomes were preserved.”

Dreams about mammoths

The researchers compared individual genes from the mammoth sample with their counterparts in modern elephants, observing differences in the activity of genes that regulate hair follicles. But elephant DNA was also needed to assemble the mammoth genome.

“Our hope and dream was to completely assemble the mammoth genome, but right now, that’s not quite where we are — we still use some information from its closest relatives to help, because the amount of data we were able to get from the mammoth was less than we normally would. necessary,” said Dudchenko. “But the fundamentals tell us that as we continue to work towards this, we will be able to do it (without the help of elephant DNA).”

Could fossil chromosomes make the dream of resurrecting the woolly mammoth a reality? “The fundamental biology we learn from this will be useful, there’s no doubt about that,” Dudchenko said. “Are we closer? One step closer, but there are still many steps to go with all kinds of considerations that go beyond the basic science.”

The researchers also hope that the same methodology used in the mammoth sample can be applied to samples from other species.

“We expect to find chromosome structures in museum samples,” said Marcela Sandoval-Velasco, a guest researcher at the Center for Evolutionary Hologenomics at the University of Copenhagen in Denmark and co-first author of the study.

“Not just permafrost specimens, because that limits a lot, but also samples from museum collections. There’s huge potential there,” he added, citing the woolly rhino, extinct lions and the passenger pigeon as some of the extinct species that scientists could discover more about in this way.

This potential allows for more discoveries, according to Pérez Estrada. “It will take a huge effort to find suitable samples, so there will be a lot of work ahead — but I wouldn’t be surprised if we discovered something new and completely different from what we have now,” she said.

“This is also a really exciting open question: What else and what other physical attributes (of DNA) can be preserved?”

Exciting discoveries

Researchers who were not involved in the study expressed excitement about the findings.

This study is the first to reconstruct the structure, or architecture, of a genome from an extinct species that lived during the last ice age, said Peter Heintzman, a paleogeneticist at Stockholm University in Sweden.

“This structural information provides insights into functions of the woolly mammoth genome that were invisible using previous genomic methods,” Heintzman said in an email.

“This advance therefore helps open an exciting new frontier in paleogenomics, the study of ancient genomes, and will likely provide further insights into how extinct species evolved, lived and disappeared.”

Given the substantial level of DNA degradation and fragmentation in ancient samples, it was surprising to see the high-quality, chromosome-level reconstruction of the mammoth genome reported in this study, he said. Dmitry Filatovprofessor of biology at the University of Oxford, in the United Kingdom.

“It is even more surprising that the researchers were able to infer which genes were active and which were off in the mammoth sample and compare this to gene expression in elephants,” Filatov said in an email. “This will certainly stimulate more research into paleogenomics in other species.”

Hendrik Poinar, director of the Center for Ancient DNA at McMaster University in Ontario, called the paper “very exciting.” Typically, with fossil remains, researchers can’t do anything remotely close to assembling a genome, Poinar said.

“I don’t know how many tissue samples will have this level of preservation,” he added in an email. “But I believe the method will make us think of new ways of extracting DNA from tissues in different ways than we are used to.”

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This content was originally created in English.

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