Mapping our genetic relationships with Neanderthals deserves a Nobel Prize

What is the relationship of primitive man to medicine? It turned out to be more than enough to win Svante Papu the Nobel Prize in Medicine on Monday for sequencing the Neanderthal genome. It may seem like an anthropology prize-worthy achievement, but scientists are already using Neanderthal DNA to drive important medical findings, and they expect more in the future.

For example, in 2020, Pääbo and Hugo Zeberg found that having a certain type of Neanderthal gene may double the risk of death from Covid-19. This gene is present in about 50% of people in South Asia and about 16% of Europeans. They later discovered another type of Neanderthal gene with a possible protective effect against Covid-19. It appears in about half of people outside Africa.

Pääbo’s work on Neanderthal DNA led to a whole new field of study of ancient DNA, and in 2010 he brought to the world a shocking discovery that violated what every student knows about Neanderthals as a dead-end branch of the family tree. Neanderthals were our ancestors’ lovers, spouses, or perhaps rape victims. One way or another, they have interbred for thousands of years and passed their genes all the way down to today’s humans.

This genetic legacy has influenced modern humans’ risk of type 2 diabetes, Crohn’s disease, lupus, and even smoking behaviour. What may seem a curiosity has opened a new window into human physiology and health.

“Some fundamental and more profound questions about human biology can be addressed directly from this information from Neanderthals,” said Richard E. Green, a biomolecular engineer who worked with Papo to decode genomes from ancient bones.

Some of the Neanderthal genes that people continue to carry have negative effects on health, and some have beneficial effects – or a combination whose overall balance depends on environmental factors such as diseases that pose the greatest threat. An ancient gene helped Tibetans adapt to living at high altitudes.

Geneticist David Reich at Harvard University recently used bones from ancient humans in our lineage to show that they carried more genes from Neanderthal crosses than people do today, suggesting that many of these genes had a detrimental effect. Among the remaining genes, scientists are still figuring out how they affect skin, hair, and disease susceptibility.

“This cross-breeding was a profound experiment with nature,” Reich said. “The legacy in this mix lives on in humans today – it injected massive amounts of genetic material into modern humans that didn’t exist before.”

Marie Claire King, a professor of genetics at the University of Washington, said Papo’s lab is now conducting exciting research into the genes that make our brains different from ours — and unlike any other species on Earth. She is best known for discovering the first breast cancer gene and for discovering in 1975 that human and chimpanzee DNA is 99% identical.

Comparing our DNA with that of other species helped us understand what different human genes do. With Pääbo’s work, she said, we have another species that is much closer to reference. Modern humans diverged from the ancestors of chimpanzees about 7 million years ago, and from the ancestors of Neanderthals about 400,000 years ago. We and Neanderthals are 99.8% genetically identical through our common ancestors, and through mixing that began about 60,000 years ago.

Finding what’s unique in the genes that govern the structure and development of the modern human brain could shed light on the roots of brain disorders and mental illness — a mystery she’s currently working on, King told me. And it can help us understand why the human mind is so creative and good at solving problems.

Pääbo’s work unlocked more of the genes of Neanderthals – it opened ways to obtain DNA from other ancient remains. When I was writing about evolution in the early 2000s, scientists were fascinated by his quest to sequence Neanderthal DNA, but thought that this minute molecule would be too degraded after tens of thousands of years to provide plenty of information.

Green said Babu was one of the rare scientists willing to take a huge risk by embarking on a project that was very likely to fail. “He envisioned technologies not yet invented that might overtake his limits,” Green said. People advised Green as a young researcher to stay away from ancient DNA, saying that such work would not go anywhere.

At the insistence of Pääbo, we now also know of a previously unknown branch of the human family, called Denisovans. Pääbo discovered our new relatives after sequencing DNA from a Siberian finger bone.

Harvard University’s Reich said it’s now understood that all humans on Earth mixed with different ancient species — Neanderthals, Denisovans and, in Africa, groups whose bones did not fossilize but whose genes left their mark. We have a different understanding of our past than we did just a decade ago, and I’m just beginning to understand the implications of it.

“These are really early days and I think it will take another decade to learn the full extent of Neanderthals’ legacy in human genetics,” Green said. It may not sound like typical biomedical research, but the recognition that the Nobel Prize brings to this field is well deserved.


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