Svante Pääbo, a Swedish geneticist, established paleogenetics, a discipline focused on studying ancient DNA (aDNA) to reconstruct the evolutionary history of species. This field aims to recover and analyze genetic material from extinct organisms, primarily hominins, to gain insights into their biology and relationship to modern humans. Pääbo’s pioneering work overcame significant technical hurdles in working with highly degraded and contaminated ancient samples. His decades-long effort culminated in groundbreaking discoveries about human origins, earning him the 2022 Nobel Prize in Physiology or Medicine.
The Founding of Paleogenetics
Recovering genetic information from ancient remains was long believed to be impossible because DNA degrades rapidly after an organism dies. Over thousands of years, the DNA molecule becomes chemically modified and breaks down into short fragments. The challenge was compounded by massive contamination, as ancient bones are saturated with microbial DNA, sometimes accounting for over 99.9% of the extracted genetic material.
Pääbo and his team developed rigorous, specialized techniques, essentially inventing the methodological framework for the field. They established “clean room” laboratories designed to prevent the introduction of modern human DNA contamination, a constant risk when handling samples. To identify authentic ancient DNA, they focused on specific chemical damage patterns unique to older fragments, such as cytosine deamination, which authenticates the ancient origin of the sequence.
Early attempts focused on mitochondrial DNA (mtDNA) because it exists in thousands of copies per cell, significantly increasing the chances of retrieval. This strategic focus allowed Pääbo to sequence a region of Neanderthal mtDNA in the mid-1990s, providing the first genetic data from an extinct hominin. These foundational methods paved the way for tackling the far more complex nuclear genome.
Mapping the Neanderthal Genome
Pääbo’s most ambitious project was sequencing the complete nuclear genome of the Neanderthal, a task many scientists dismissed as unrealistic. In 2010, his team published the first draft sequence of the Neanderthal genome, derived from bones tens of thousands of years old. This achievement provided the first comprehensive genetic blueprint of an extinct hominin species.
The sequenced genome allowed for direct comparisons with modern human DNA, revealing that Neanderthals were a distinct, closely related lineage, not direct ancestors. Analysis offered insights into Neanderthal characteristics, suggesting they may have possessed the FOXP2 gene variant for speech and exhibited variations in skin and hair pigmentation genes. The data established that Neanderthals and modern humans had diverged from a common ancestor an estimated 270,000 to 440,000 years ago.
This sequencing breakthrough provided definitive proof that modern humans and Neanderthals interbred. The comparison showed that non-African modern human populations carry measurable percentages of Neanderthal DNA. This finding overturned the long-held model of complete replacement, confirming a more complex history of intermixing outside of Africa.
The Discovery of Denisovans
The power of Pääbo’s paleogenetic approach was dramatically demonstrated with the discovery of the Denisovans. In 2008, a tiny fragment of a finger bone and a tooth were discovered in Denisova Cave in southern Siberia. The bone fragment was too small and non-descript to be classified morphologically by traditional paleoanthropology.
Pääbo’s team successfully extracted and sequenced the DNA from this 40,000-year-old fragment, revealing a genetic sequence distinct from both Neanderthals and modern humans. This genetic profile represented a previously unknown hominin lineage, named Denisovans after the cave where the remains were found. It was the first time a new group of human relatives was identified solely through genetic analysis, rather than anatomical features.
The Denisovan genome showed they were a sister group to Neanderthals, sharing a more recent common ancestor than either did with modern humans. Analysis of the few recovered remains suggested the Denisovan population had very low genetic variation, indicating they were likely never a large population. The sequencing also showed that Denisovans interbred with the ancestors of some modern human populations, particularly those in East Asia and Melanesia.
Implications for Modern Human Evolution and Recognition
The implications of Pääbo’s work lie in archaic introgression, the transfer of genes between different species through interbreeding. Genetic evidence confirmed that when modern humans migrated out of Africa approximately 70,000 years ago, they encountered and interbred with both Neanderthals and Denisovans. Today, non-African modern humans typically carry 1% to 4% of Neanderthal DNA, and populations in Melanesia can have up to 6% of Denisovan DNA.
These inherited archaic genes have had a lasting impact on modern human biology and health. Neanderthal gene variants have been linked to traits like skin and hair pigmentation, metabolism, and certain sleeping patterns. Crucially, many Neanderthal and Denisovan genes are involved in the immune system, providing adaptations to new pathogens as modern humans spread across Eurasia.
A specific Denisovan gene variant, inherited by modern Tibetans, helps them adapt to high altitudes by regulating hemoglobin concentration. Conversely, some Neanderthal segments have been associated with increased risk for certain diseases, including Type 2 diabetes, Crohn’s disease, and severe Covid-19 symptoms. Pääbo’s research provided a direct genetic connection between our deep past and our contemporary health.
The creation of paleogenetics fundamentally changed the understanding of human origins from a simple linear progression to a complex tapestry of intermingling populations. Svante Pääbo was awarded the 2022 Nobel Prize in Physiology or Medicine for his discoveries concerning the genomes of extinct hominins and human evolution. This recognition underscored how paleogenetics provided definitive genetic proof for the interconnectedness of human history.