Dental proteins extracted from six Homo erectus individuals who lived in what’s now China 400,000 years ago provide the first genetic evidence that H. erectus mated with Denisovans, thus illuminating a landmark moment in human evolution (Nature 2026, DOI: 10.1038/s41586-026-10478-8).
Homo erectus is one of the longest-lasting human relatives, originating around 2 million years ago in Africa and surviving until as recently as 108,000 years ago. It was the first hominin to migrate out of Africa, spreading into Eurasia and reaching as far as Java in Indonesia. Knowing its molecular profile is crucial for understanding hominin biology. Yet the only previous H. erectus data (peptides from a 1.77-million-year-old tooth discovered in Dmanisi, Georgia) lack the specific amino acid markers needed to chemically distinguish H. erectus from other hominins.
Qiaomei Fu, a paleogeneticist at the Chinese Academy of Sciences’ Institute of Vertebrate Paleontology and Paleoanthropology, and her colleagues studied seven teeth excavated in China: one Denisovan tooth and six 400,000-year-old H. erectus teeth from three different sites. The team extracted enamel proteins from all the samples and analyzed them via liquid chromatography/tandem mass spectrometry, ultimately zeroing in on nine proteins.
Analysis of the protein amelogenin revealed that all the samples, barring one, belonged to males, including the Denisovan.
The researchers struck gold when they identified two important amino acid sequence variants in a protein called ameloblastin. The first variant, amino acid alanine replaced by glycine at position 253, was found in all six H. erectus samples. It is completely absent in modern humans, Neanderthals, Denisovans, and even the earlier H. erectus found in Dmanisi, Georgia, thus making it a strong marker for East Asian H. erectus.
“This new variant A253G in AMBN [alanine replaced by glycine at position 253] is an important mutation for Homo erectus,” Fu says in an email. “It would be interesting to know when it appears.”
An archaic tryst unveiled
The second variant, methionine replaced by valine at position 273, is shared with Denisovans. The researchers believe that H. erectus interbred with Denisovans and passed on this variant to them. Interestingly, this signature persists in a small fraction of Homo sapiens, showing a direct link to H. erectus. “This is the first time that the phylogenetic information for Homo erectus has been identified,” Fu says.
Bence Viola, a paleoanthropologist at the University of Toronto who wasn’t involved in the study, calls it “very exciting.”
He applauds the researchers for determining sex “from single teeth just based on the proteomes” and being able to “show [gene flow] with proteins, because that has not been done before.”
Viola explains that small amounts of archaic DNA can have significant biological impacts. A prime example is the EPAS1 gene variant, which confers advantages for living at high altitudes, such as preventing the dangerous thickening of blood by keeping hemoglobin levels relatively low. This variant originated in the Denisovans and today exists in a small percent of the modern human population, including 80% of Tibetans.
