The ghost in your genes
Inside the Max Planck Institute for Evolutionary Anthropology, a team led by geneticist Svante Pääbo accomplished a task once considered impossible. They sequenced the entire 3-billion-base-pair genome of a Neanderthal, our closest extinct relative. The project, initiated in 2006, faced immense technical hurdles. Ancient DNA is not pristine; it shatters into tiny fragments over tens of thousands of years and becomes heavily contaminated with microbial DNA. Worse, any handling by modern humans risks overwhelming the sample with our own DNA.
To solve this, Pääbo's group developed new methods, including working in ultra-sterile clean rooms and tagging DNA fragments with unique identifiers to filter out contaminants. The primary genetic material came from less than half a gram of bone from three female Neanderthals found in Vindija Cave, Croatia. By 2010, the team published its first draft sequence. The results showed that gene flow from Neanderthals to modern humans occurred. People with ancestry outside of Africa carry between 1 and 4 percent Neanderthal DNA, a direct genetic echo of contact between 47,000 and 65,000 years ago. For this work, Svante Pääbo was awarded the Nobel Prize in Physiology or Medicine in 2022.
A new human family tree
The work in Leipzig did not stop with Neanderthals. While analyzing a 40,000-year-old finger bone from Denisova Cave in Siberia, Pääbo's team discovered a completely new group of extinct hominins: the Denisovans. The genome from this tiny bone fragment revealed a population distinct from but related to Neanderthals. Subsequent analysis showed that Denisovans also interbred with early Homo sapiens. Today, people of Melanesian and Australian Aboriginal descent carry between 4 and 6 percent Denisovan DNA.
The Neanderthal and Denisovan genomes provide a record of the deep past. The inherited genes are not silent; they have physiological relevance today. Some Neanderthal variants are associated with the production of keratin, a protein that gives toughness to skin and hair. Other genes affect our immune systems, affecting how we respond to pathogens. For example, specific Toll-like receptor genes (TLR1, TLR6, and TLR10), which are important for the body's first line of defense, show high levels of Neanderthal ancestry. Some inherited genes are also linked to an increased risk for conditions like type 2 diabetes and Crohn's disease.