the ‘impossible task’ of recreating Neanderthal DNA

The winner of the 2022 Nobel Prize in Medicine created a discipline that contributed to this important discovery: paleogenomics.

Imagine that all the pages of a dictionary were destroyed in a paper shredder and you had to rebuild all the work.

Suppose, in addition, the thousands of shredded strips from that dictionary were mixed with those from thousands of other books, which were also shredded.

To make matters worse, over this mountain of cut paper, a cup of coffee was poured.

As you can imagine, the result of this is a huge glued ball that mixes up millions of letters and tiny segments of text, which has become unreadable and confusing.

But is it possible to restore this dictionary?

This was the figure of speech Swedish scientist Svante Pääbo used in the documentary First Peoples (“First Peoples”, in free translation), of the American public television network PBS, to describe the difficulty he faced: the reconstruction of Neanderthal DNA after tens of thousands of years of the extinction of this species.

The passage of time, the corrosion of the possible remains of these human relatives of the Homo sapiensinteraction with bacteria and fungi over hundreds of centuries and contact with modern humans would make it impossible to reorganize the genetic pieces.

“There are all kinds of DNA damage that can cause you to determine wrong sequences, especially when starting with a few molecules. There is also contamination of the material by human DNA, which is almost everywhere,” wrote Pääbo in a published article. in 1989.

But Pääbo and his team managed to do what seemed unlikely. Thanks to that, he won the 2022 Nobel Prize in Medicine on Monday (3/10).

“Through his pioneering research, Svante Pääbo has achieved the impossible: sequencing the Neanderthal genome, an extinct relative of modern humans,” the Nobel committee declared in announcing the decision.

But how did he achieve this feat?

The key is in Ancient Egypt

To understand the process that led Pääbo, 67, to reconstruct the Neanderthal genome, you have to go back to his adolescence.

When he was 13, his mother took him on vacation to Egypt.

There, he became fascinated with the country’s ancient culture and archeology and returned convinced that he would become an Egyptologist.

When it was time to start graduation, Pääbo entered the University of Uppsala, 70 kilometers northwest of Stockholm, the capital of Sweden, and really began to study Egyptology.

However, after two years, he realized that this was not what he aspired to in life. His career was oriented towards the study of hieroglyphic grammar (a form of writing by symbols adopted in Ancient Egypt), and he dreamed of discovering mummies and pyramids.

“The work wasn’t the romantic, Indiana Jones kind of work I thought it was,” Pääbo told the BBC a few years ago.

That’s why he went on to study medicine. In his doctorate, he decided to study molecular genetics, which led him to link the interest he had had since adolescence to the professional field.

“I started to realize that we had all these technologies for cloning DNA, but no one seemed to have applied them to archaeological remains, particularly Egyptian mummies,” Pääbo said in a profile published by the US National Academy of Sciences.

From these tools, he could create a genomic time machine.

The restlessness led him to study the genome of mummies and, a few years later, move to the United States to investigate ancient DNA at the University of California at Berkeley.

He then followed work in Munich, Germany, where he devoted himself to cave-dwelling mammoths and bears.

Despite all the difficulties, Pääbo did not give up. Over time, he set out to do something much more ambitious: decipher Neanderthal DNA and what sets it apart from modern humans.

Inadvertently, he practically created a new discipline in science: paleogenomics.

Remnants of 40 thousand years

In the late 1990s, Pääbo was hired by the Max Planck Institute for Evolutionary Anthropology, located in Leipzig, Germany.

He was already working with parts of Neanderthal DNA. In the new place of work, however, the offer increased: the scientist would have the opportunity to directly investigate the DNA nucleus of these close relatives of our species.

“At the new institute, Pääbo and his team constantly improved the methods for isolating and analyzing DNA from archaic bone remains. The research team took advantage of new technological advances, which made DNA sequencing very efficient”, details the committee in charge of awarding the Prize. Nobel Prize in Medicine.

The study of the Neanderthal genome used bone fragments of this species that have been preserved for more than 40,000 years. From this material, it was possible to obtain a sufficiently good amount of DNA.

One factor that contributed to the success of the investigation was cannibalism among these hominids.

“When we analyzed the samples, we noticed that we were often more successful with bone fragments that actually had cut marks or were deliberately broken. According to paleontologists, this suggests that these individuals had been eaten,” Pääbo told the BBC.

“If you separate the bones from the meat and throw them in the corner of the cave, where they dry quickly, they will have less microbial activity and will be preserved,” he added.

“We have cannibalism to thank for the success of our project.”

Pääbo used DNA sequencing technology and created laboratories with high standards of cleanliness to prevent sample contamination.

He then analyzed millions of pieces of genetic material and used statistical techniques to isolate them from modern genes, coming from humans, bacteria and fungi.

With this, he not only reconstructed the Neanderthal genome, but also found links between this genetic material and that of the modern human.

This, in turn, proves that the Homo sapiens had sex and descendants with Neanderthals? and this interaction spawned new species, such as the Denisovans who lived in Asia.

This series of discoveries led the meticulous Swedish researcher to win one of the most distinguished awards in the world.

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