Scientists Create Highly Detailed 3D Model of Extinct Woolly Mammoth DNA

A woolly mammoth that died in Siberia 52,000 years ago left behind an extraordinarily well-preserved body, which was freeze-dried almost instantly in the severe cold of a Siberian winter. In fact, this animal was so perfectly preserved that scientists were able to determine not just the sequence of a sample of its DNA, but the actual three-dimensional structure of its genome.

In a new paper just published in the journal Cell, an international team of researchers led by experts from the Center for Evolutionary Hologenomics at the University of Copenhagen explained the unusual circumstances that allowed them to achieve this breakthrough. Representing an astonishing scientific achievement, this is the first time genetic researchers have been able to examine ancient DNA in three-dimensional form, which reveals invaluable information about the structure of the extinct animal’s genetic heritage.

 

 

For the first time, scientists have determined the 3D genome structure of a woolly mammoth’s (Mammuthus primigenius) skin cells. (Photo by Love Dalén, Stockholm University)

The problem with trying to unlock the genetic code of an ancient animal is that the DNA that does survive in its skeletal remains is usually highly degraded. What can be detected are only isolated sections of genetic material, which as pieces of a much larger puzzle can be difficult to put together. But in this new study, the scientists were able to determine more precisely where the various pieces should be inserted on the puzzle board, making it possible to create models that look very much like the mammoth’s genome would have looked.

“Until now, we could only read small fragments of ancient DNA,” study co-author Juan Antonio Rodriguez, an assistant professor of hologenomics at the University of Copenhagen in Denmark, told Live Science. “These fragments were about 100 letters of DNA, but we did not know what order they had in the mammoth genome. It is like separated pages of a book, but without the page number.”

But now the pages have been put in their proper order, in the context of 3D imagery that previously could only be created for animals that died much more recently.

Eventually, scientists hope to use this kind of advanced analysis to recreate the woolly mammoth genome in its entirety. This could presumably be done by cross-referencing DNA samples taken from different mammoth remains, until all the letters of DNA the animal possessed have been identified and put in their proper places on a three-dimensional model. Once this has been done, it could conceivably lead to the woolly mammoth being brought back to life (although this admittedly remains a long way off).

Marianne Dehasque (Love Dalén/Stockholm University)

Putting the Genetic Puzzle Pieces Back Together

Scientists discovered the woolly mammoth that provided the DNA used to make the 3D model in 2018, near the town of Belaya Gora in Siberia’s Sakha Republic. The frozen animal specimen was still covered with hair, which revealed how quickly and thoroughly it had been freeze-dried after its death.

Dating procedures established that the animal lived 52,000 years ago, in the late Pleistocene. Because of its almost lifelike appearance, its discoverers even gave it a name, calling it “YakInf.”

The giant mammoth, which was identified as an adult female, was freeze-dried in a way that crystalized its cells and chromosomes along with its skin and bones. In this extremely dehydrated state, the mammoth’s tissues didn’t degrade much at all, leaving behind relatively pristine genetic samples that were perfectly suited for DNA extraction and analysis.

The scientists involved in this study took DNA samples from a piece of skin removed from behind the mammoth’s ear, and they were delighted to discover just how well-preserved this genetic material actually was. They analyzed it using High-Throughput Chromosome Conformation Capture Technique (Hi-C), a sophisticated technology that allows experts to determine how fragmented DNA samples might have once been joined together. Normally this technology is only used on modern DNA samples, where there is less degradation, but the researchers found a way to adapt the technology to make it work with the sections of ancient mammoth DNA.

Using this modified form of Hi-C analysis, which they labeled PaleoHi-C, the team was able to show that woolly mammoths had 28 pairs of chromosomes in their genomes, just like modern elephants.

Most importantly, the scientists were able to discover “how exactly those chromosomes were folded in 3D in the mammoth skin nuclei, which is very cool, because… we know that the way chromosomes are folded has a lot to do with cell function,” study co-author Olga Dudchenko, an assistant professor in the department of genetics at Baylor College of Medicine in Houston, Texas, explained to Live Science.

The patterns of folding revealed in the 3D model can be used to determine which genes were active at the time of the mammoth’s death. By making comparisons to gene activity in elephants, a close living relative of the woolly mammoth, scientists should be able to detect important similarities and important differences between the two species, which may ultimately aid in efforts to bring the mammoth back to life (if and when such efforts take place).

Woolly mammoth tusk in Siberia. (Love Dalén/Stockholm University)

Welcoming Back the Woolly Mammoth … Someday … Maybe

The study authors were careful to note that supporting woolly mammoth de-extinction efforts was not the primary motivation for their work. Mainly the research was performed to stretch the limits of what is possible in ancient DNA analysis, which is essential for tracing evolutionary timelines more accurately and for learning more about the true nature of the flora and fauna that existed in the distant past.

Nevertheless, the detailed study of the mammoth’s genetic architecture “is one more step” toward bringing the creature to life in the 21st century, Rodriguez acknowledged.

“But there are many other known and unknown steps that scientists need to figure out before bringing a mammoth back,” he cautioned, reiterating that such a development is unlikely to take place any time soon.

Top image: Woolly mammoth scene.    Source: Beth Zaiken/Stockholm University

By Nathan Falde