Scientists have always been fascinated by the question of human origins: When and where did modern humans—Homo sapiens—first appear? What distinguishes us from other members of the genus Homo and enabled us to develop such unprecedented culture and society?
Indeed, hardly any question fascinates humanity as much as our own roots. For thousands of years, clerics, scholars and philosophers have been racking their brains about where we come from, who are we and where are we going. The French painter Paul Gauguin was so captivated by that line of inquiry that he even dedicated a painting so named in the 19th century. The work, which deals with both the meaning and the transience of life, remains his most famous.
We have come a lot closer to answering these big questions thanks in part to the work of the paleogeneticist Svante Pääbo. He achieved what others had long thought impossible: he decoded the genome of Neandertals, a relative of modern humans who went extinct around 30,000 years ago. The Nobel Assembly at the Karolinska Institute in Stockholm honored him this year with the Nobel Prize in Medicine or Physiology for his contribution to the study of human evolution.
Ancient DNA Is Difficult to Analyze
When Pääbo began working with ancient DNA in the 1980s, the discovery of Neandertals was long a thing of the past. The first fossils of early humans had already been unearthed in the mid-19th century. At first glance this species seemed to be more closely related to modern humans than almost any other. But just how Neandertals were related to Homo sapiens was a subject of repeated controversy in the decades following the discovery. For example, some wondered whether Neandertals could possibly have been an ancestor of modern humans—a hypothesis that most experts have since rejected.
Genetic data could undoubtedly shed light on the connection between modern humans and Neandertals. Analyzing the genome of a living species was one thing, but obtaining genetic samples of a species extinct for tens of thousands of years was quite another. Over time, DNA changes chemically and gradually breaks down into short fragments. So after thousands of years, only traces of it remain among bone samples, and those traces are usually heavily contaminated with foreign DNA.
Journey to the Neandertal
That didn’t deter Pääbo. As early as 1984, while doing his doctorate at Uppsala University, he caused a small sensation when he managed to isolate DNA from the cells of a 2,400-year-old Egyptian mummy for the first time. Fearing that his doctoral supervisor would forbid him from doing the research, he secretly carried out his studies at night and on weekends, as he later explained. But by the time the journal Nature picked up the results, everyone was talking about his work. At the time it was the only paper published on DNA from fossil tissues.
Soon after, Pääbo joined Allan Wilson’s group at the University of California, Berkeley. Here he dealt, among other things, with the genome of extinct animals such as mammoths and cave bears. But Neandertals were always among his chief interests, Pääbo told Spektrum der Wissenschaft in 2008. Ultimately, he wanted to find out what makes humans human, and which genetic changes contributed to human evolution.
In 1990 he continued this research at the University of Munich. There he decided to focus first on mitochondrial DNA, copies of which are present in a significantly higher number inside the cell nucleus compared to DNA. In 1997 he finally succeeded in isolating the genetic material from an approximately 40,000-year-old Neanderthal bone that was part of a Neandertal skeleton found near Düsseldorf in the 1850s. This was the first time the world had access to a piece of Neandertal genome.
Comparisons with the mitochondrial DNA of modern humans and chimpanzees soon showed that the Neandertals differed genetically from both species: Homo sapiens and Homo neanderthalensis did not share more than 10 percent of their genes.
Genes in Common
In contrast to the DNA from the cell nucleus, the mitochondrial genome is small. It contains only a fraction of all the genes that a living being possesses and is therefore of limited usefulness. Further progress in the field therefore depended on obtaining the complete Neandertal genome. In order to clear the last hurdle, Pääbo, then the newly appointed director of the recently founded Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, continued to refine his methods over the coming years. In 2010 he finally made his breakthrough and was able to present the world with the first version of a fully sequenced Neandertal genome.
Pääbo and his team’s research indicated that the last common ancestor of modern humans and Neandertals must have lived around 800,000 years ago. They also proved gene flow from Neandertals to modern humans: both species apparently interbred in the millennia that they lived simultaneously on earth, primarily in Europe and Asia, where the human genomes sequenced contain 1 to 4 percent Neandertal genes.
Pääbo and his team also sequenced the genome of Denisova, a hominin whose fossils were found in 2008 in the Denisova Cave in the Altai Mountains in Siberia. The group was not only able to show that the Denisova was a new, previously unknown early human species, but also that the Denisova maintained close contact with ancestors of modern humans; in some regions of Southeast Asia, humans share up to 6 percent of their genes with the extinct Denisovans.
The Circle Closes
Today, Pääbo is rightly regarded as one of the founders of paleogenetics. “His work has revolutionized our understanding of the evolutionary history of modern humans,” stated Martin Stratmann, president of the Max Planck Society, in a press release. Chris Stringer of the Natural History Museum in London offered similar praise; that Pääbo is now receiving the Nobel Prize is great news, the paleoanthropologist told Nature.
Pääbo’s work has not only shed new light on our past. Further studies indicate that our Neandertal heritage also influences our present. For example, some of the genes seem to have an impact on how the immune system reacts to various pathogens. In 2021, Pääbo and his team made headlines when they reported that people with a specific Neandertal variant on the third chromosome were at a higher risk of developing severe COVID-19.
The answers to the two questions of where we come from and where we are going might end up being more similar than we thought.
This article originally appeared in Spektrum der Wissenschaft and was reproduced with permission.
