What did it mean genetically, and to some degree behaviorally, to be a Neanderthal? Were they related to Homo sapiens and, if so, how? What additional knowledge could we modern humans gain from knowing more about the genomes of Neanderthals?
These kinds of questions have spun around in the heads of anthropologists for years. For much of that time, Neanderthals were viewed as knuckle-dragging, troglodyte-like primitive ancestors of H. sapiens. However, archeological and fossil discoveries over much of the past half-century have put those images to rest in lieu of Neanderthals as smart hunters who weathered severe ice ages, caregivers for their sick, injured, and elderly and appear to have buried their dead, and creative in terms of weapon-making for hunting and survival and most likely creating art.
But the transformative advance in understanding Neanderthals came from Svante Pääbo, PhD, a Swedish paleogeneticist who runs a lab staffed by a group of colleagues at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. He received the Nobel Prize in Physiology or Medicine yesterday for his “discoveries concerning the genomes of extinct hominins and human evolution,” and is the first paleoanthropologist to do so.
Pääbo, 67, whose father was a Nobel Prize winning biochemist, thought the Nobel Prize call from Sweden was a prank or something concerning his summer house.
“So I was just gulping down the last cup of tea to go and pick up my daughter at her nanny where she has had an overnight stay,” Pääbo said in a recording posted on the Nobel website. “And then I got this call from Sweden and I of course thought it had something to do with our little summer house … I thought the lawn mower had broken down or something.”
He added that he never thought he would win a Nobel although he had received a number of other prizes.
In February 2009, Pääbo and his coworkers reported that they completed the first draft version of the Neanderthal genome. They sequenced over three billion base pairs with 454 Life Sciences, a company acquired in 2007 by Roche which closed 454 down six years later. Production, however, remained in operation until mid-2016.
A little over a year later, Pääbo and colleagues published a report about the DNA analysis of a finger bone found in the Denisova Cave in Siberia. The bone belonged to an extinct member of the genus Homo that had not yet been recognized, the Denisova hominen. The discovery marked the first time a previously unknown early human ancestor was discovered by means of DNA analysis.
On May 7, 2010, Pääbo’s group published a draft sequence of the Neanderthal genome in Science. He and his team also concluded that there was probably interbreeding between Neanderthals and Eurasian (but not Sub-Saharan African) humans. There is general mainstream support in the scientific community for this theory of interbreeding between archaic and modern humans. This admixture of modern human and Neanderthal genes is estimated to have occurred roughly between 50,000 and 60,000 years ago in Southern Europe.
In modern humans of European or Asian descent, approximately 1–4% of the genome was contributed by Neanderthals.
Scientific community utilizes the Pääbo lab’s discoveries
Pääbo also found that gene transfer had occurred from the extinct Denisovans to Homo sapiens following the migration out of Africa around 70,000 years ago. His early research gave rise to an entirely new scientific discipline—paleogenomics. By revealing genetic differences that distinguish all living humans from extinct hominins, paleogenomics became a distinct field of study that provides the basis for exploring what makes us uniquely human. Pääbo’s discoveries are utilized by the scientific community to better understand human evolution and migration.
The Pääbo team’s work also led to other major insights on archaic gene sequences from our extinct relatives that influence the physiology of today’s humans. For example, the Denisovan version of the gene EPAS1 confers an advantage for survival at high altitude and is common among present-day Tibetans. Other examples are Neanderthal genes that affect our immune response to different types of infections.
On September 30, 2020, in an article (“The major genetic risk factor for severe COVID-19 is inherited from Neanderthals”) in Nature, Pääbo and colleagues wrote that a “recent genetic association study identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative) comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization.
“Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.”
Reactions from biological anthropologists
“My hat goes off to Svante,” Ian Tattersall, PhD, a globally-known paleoanthropologist and a curator emeritus with the American Museum of Natural History, told GEN. Tattersall has written extensively on human evolution in academic journals, newspapers, magazines, and numerous books, his most recent being “Understanding Human Evolution” (Cambridge University Press, 2022).
“[Pääbo] has had a profound effect on the study of human evolution. Three decades ago, he had a vision that many thought Quixotic at the time. But he steadfastly stuck by that vision, assembled a team of gifted collaborators, and in the end has created an entire subfield of paleoanthropology that has both complemented and extended the traditional study of the human fossil record. Molecular paleoanthropology, his brainchild, has generated a body of otherwise unobtainable knowledge without which our appreciation of the human biological past would be much poorer.”
Chris Stringer, PhD, a British paleoanthropologist who works at the Natural History Museum in London, said in a Museum press release that “the use of ancient DNA made a huge contribution to the study of human evolution.”
He cited past studies that focused on whether H. sapiens had or had not evolved from Neanderthals. Resolving disagreements over fossils was difficult because interpretations of similar features could vary significantly. Pääbo and his colleagues developed novel methods to help extract ancient DNA from old specimens and remove contamination accumulated across thousands of years.
“The real breakthrough that Pääbo’s group made was in dealing more effectively with the virtually ubiquitous presence of contaminating ‘modern’ DNA,” Stringer told GEN.
“Until 40 years ago, it was thought that Neanderthals were a subspecies of H. sapiens, and not their own species,” Stringer explained in the museum press release. “Work I was involved in during the 1970s and 1980s moved the Neanderthals further away from us and asserted that they could be a different species, which Pääbo’s research affirmed.”
“It is one of the most well-deserved awards I’ve ever heard of or seen,” noted Todd Disotell, PhD, professor of biological anthropology, University of Massachusetts (Amherst). “It’s important to keep in mind, however, that the work has been carried out as a broad, global collaborative effort.”
Disotell humbly admits that he, along with many other anthropologists, did not originally believe that Neanderthals mated with modern humans. “But Svante and others later came out with more detailed genomic data as the sequencing technology improved” that clearly showed there was introgression of Neanderthal DNA in the human genome. He also believes the Nobel Prize will help in getting more funding for other projects involving ancient DNA.
“Right now, the Neanderthal DNA we have comes from Central and Western Europe, and Denisovan DNA was found in a finger bone from a cave in Siberia,” continued Disotell. “So I say, ‘congrats Svante,’ and keep up the good work because this has implications on a worldwide level. We have to move on and sample other populations all over the world, specifically wherever modern human immigrants entered. We need to try to figure out what the genomic profile was of the original inhabitants in particular regions. This will have real world and direct medical implications today and in the future.”