Homo erectus enamel proteins reveal a link with the Denisovans

There is no DNADNAThe molecule carrying genetic information, used to reconstruct kinship between species.→ from Homo erectusHomo erectusAncient human species, the first hominin to leave Africa and the maker of the earliest Acheulean handaxes.→. The fossils of this species, which populated AfricaAfricaThe cradle of humankind: the continent where the first hominins appeared, then Homo sapiens around 300,000 years ago, before the expansion to the rest of the world.→ and Asia for almost two million years, are too old and spent too long in warm climates for their genetic material to survive. But tooth enameltooth enamelThe hardest tissue in the body, laid down in rhythmic layers during tooth formation that preserve a precise memory of time.→, the hardest substance in the human body, preserves something else: fragments of protein. In the journal Nature, a team led by Qiaomei Fu of the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences in Beijing has extracted these proteins from six fossil teeth found in China. Their analysis reveals an unexpected link with another vanished humanity, the DenisovansDenisovanAn extinct human population, cousin of the NeanderthalsNeanderthalsA fossil humanity of Eurasia, robust and cold-adapted, extinct around 40,000 years before present.→, identified in 2010 from the DNA of remains in Denisova Cave (Siberia).→.¹²

Six teeth from three Chinese sites

The teeth come from three famous sites in Chinese palaeoanthropologyPalaeoanthropologyThe science that studies human evolution from the fossil remains of hominins (bones, teeth, footprints) and their context, to reconstruct our biological origins.→. The first is Zhoukoudian, near Beijing, the cave where "Peking Man", long known as Sinanthropus pekinensis, was discovered in the 1920s and 1930s. The second is Hexian, in Anhui province, where a Homo erectus skull was unearthed in 1980. The third, Sunjiadong in Henan province, is less well known to the general public.¹²

The fossils are generally dated to around 400,000 years ago, although the chronology of these sites is still debated. At Zhoukoudian, estimates vary with the method used, and at Sunjiadong the age rests mainly on the associated fauna.³ The six teeth were attributed to Homo erectus on the basis of their shape and context, like the skulls found at the same sites.

Peking Man, a turbulent history

The choice of Zhoukoudian is no accident. It is one of the most famous sites in the history of palaeoanthropology. From 1927 onwards, excavations led by Chinese and Western researchers uncovered dozens of individuals there, including several skullcaps, along with stone tools and possible traces of fire. Peking Man became one of the pillars of our knowledge of Homo erectus in Asia.

But most of these fossils disappeared in 1941. As war raged between China and Japan, the crates meant to take them to safety in the United States vanished and were never found. All that remains are casts and the meticulous descriptions published by the anatomist Franz Weidenreich. The teeth analysed today are among the few original Zhoukoudian remains that stayed in China and are still available to researchers.

PalaeoproteomicspalaeoproteomicsThe study of ancient proteins preserved in fossils; more resistant than DNA, they allow remains to be identified where the genome has vanished.→, beyond DNA

Ancient DNAAncient DNAGenetic material preserved in old remains, often degraded, sequenced with cutting-edge techniques.→ has revolutionised our knowledge of Neanderthals and Denisovans. But it has a limit: it degrades over time, and all the faster in warm climates. The oldest known human DNA, from the fossils of the Sima de los HuesosSima de los HuesosA natural shaft at Atapuerca (Spain) that yielded over 6,500 bones of at least 29 Homo heidelbergensis individuals dated to −430,000: the largest Middle Pleistocene human fossil assemblage.→ in Spain, is around 430,000 years old and survived thanks to the constant coolness of a cave.

Proteins, by contrast, last much longer, especially when they are locked inside tooth enamel. Over the past decade or so, palaeoproteomicsPalaeoproteomicsThe study of ancient proteins preserved in fossils (bone, tooth enamel); can reveal species or sex when DNA is gone.→, the study of ancient proteins by mass spectrometryMass spectrometryA technique that measures the mass of molecular fragments very precisely in order to reconstruct their composition, here the sequence of proteins.→, has made it possible to analyse fossils more than a million years old. Proteins are chains of amino acids whose sequence is dictated by genes. Reading that sequence therefore means indirectly reading a small part of the genome.

Enamel is particularly well suited to this approach. It is almost entirely mineral, formed of tightly packed crystals of hydroxyapatite, and the few proteins it contains are trapped within that mineral lattice, sheltered from water and bacteria. In recent years, enamel proteins have been recovered from Homo antecessor in Spain, some 800,000 years old, and from even older fossils in Africa and Asia. Each of these studies has made it possible to place a fossil on the human family tree when its DNA had long since vanished, an achievement that would have seemed impossible only fifteen years ago.

Qiaomei Fu's team, pioneers of ancient DNA in China, identified nine enamel proteins in the teeth studied.² They were also able to determine the sex of the individuals. Some enamel proteins, the amelogenins, exist in two forms, one encoded by the X chromosomeX chromosomeOne of the two sex chromosomes, present in two copies in females and a single copy in males.→ and the other by the Y chromosome. Five of the six individuals carried the Y-chromosome signature: they were male.³

A signature never seen before

The most striking discovery concerns ameloblastin, a protein involved in the formation of enamel. All six individuals share two variants of this protein that set them apart from every other human studied so far.²

The first, called A253G, replaces one amino acid, alanine, with another, glycine. It had never been observed in any other human or any other primate. The authors propose it as a molecular marker for these East Asian populations. It also shows that the individuals from the three sites, several hundred kilometres apart, belonged to a single population or to related populations.¹²

The Denisovan link

The second variant, M273V, replaces methionine with valine. Until now it was known only in Denisovans, the archaicArchaicRefers to an ancient, now-extinct human population or form (Neanderthals, Denisovans, ghost lineages), as opposed to anatomically modern humans.→ humans identified in 2010 from the DNA of a finger bone found in Denisova Cave in the Siberian Altai.¹ The genomes of the individuals Denisova 3 and Denisova 25 carry the corresponding mutation, and the dental proteins of the Harbin skull from northern China and of the Penghu jaw, dredged up off Taiwan, contain it too.³

How can Homo erectus and Denisovans share this feature? For Qiaomei Fu and her colleagues, the variant passed from Homo erectus to the Denisovans through interbreedingInterbreedingGenetic mixing between human populations or species; between Neanderthals and Homo sapiens it left 1 to 2% of Neanderthal DNA in non-Africans.→, when the two groups met in East Asia.¹² "Given that both groups were close in space and time, it is a reasonable suggestion," says palaeoanthropologist Tanya Smith of Griffith University in Australia.²

The mysterious superarchaic ghost

This hypothesis connects with an old genetic puzzle. About a decade ago, while analysing the Denisovan genome, geneticists spotted fragments of DNA from an even older population, which they nicknamed "superarchaic" or "ghost" because they could not identify it. This population would have split from the human lineage long before the common ancestors of Neanderthals, Denisovans and Homo sapiensHomo sapiensThe present-day human species, which emerged in Africa around 300,000 years ago, the only surviving human lineage after the extinction of Neanderthals and Denisovans.→.²

Homo erectus, present in Asia for more than one and a half million years, was the ideal candidate. The new data strengthen that idea. "We realized maybe this is the super-archaic," says Qiaomei Fu.² And the story does not end there. Denisovans in turn interbred with Homo sapiens, and the M273V variant is found today in a small fraction of modern humans, notably in Southeast Asia and Oceania.¹² A tiny trace of Homo erectus may therefore survive in our own bodies.

What if these teeth were Denisovan?

Not all specialists share this reading. For palaeoanthropologist John Hawks of the University of Wisconsin-Madison, the question is far from settled. He praises the consistency of the data, noting that "it's challenging to get that kind of data from ancient enamel," but proposes another interpretation.²

"I don't think these teeth are Homo erectus," he writes on his blog. Their age, around 400,000 years, falls in his view in "prime Denisovan time". If the teeth share a variant with Denisovans, it may simply be because they belong to Denisovans, or to a population on their lineage.³ He stresses that the available information is thin, just two amino acids, and that the shape of the teeth does not rule out a Denisovan identity. He even doubts that the Zhoukoudian and Hexian skulls can be securely attributed to Homo erectus.³

John Hawks does not, however, reject the hypothesis of ancient interbreeding between Homo erectus and Denisovans, which he considers plausible. But he points out that the share of superarchaic ancestry in Denisovans is small, which makes its direct detection in a handful of proteins unlikely. In the end, he considers that both scenarios, Homo erectus or Denisovan, remain possible.³ A genetic variant can also arise independently in two populations by sheer coincidence.²

The puzzle of the Chinese fossils

This debate illustrates a wider difficulty. Human fossils from China dated between 800,000 and 100,000 years ago show a great diversity of forms, which palaeoanthropologists struggle to classify. Some have been placed in Homo erectus, others in vaguer categories such as "archaic Homo". The Harbin skull, described in 2021 as Homo longiHomo longiA hominin group defined in 2021 from the Harbin skull (Dragon Man), often linked to the Denisovans.→, was linked to the Denisovans in 2025 thanks to its proteins and its mitochondrial DNA.

Palaeoproteomics now offers a way to sort these fossils by something other than their shape alone. Each new tooth analysed will add a piece to the puzzle. The study's authors hope in particular to obtain proteins from older Chinese fossils, unambiguously attributed to Homo erectus, which would make it possible to check whether the M273V variant was already present before the Denisovans appeared.²

An Asia full of cousins

Whichever interpretation prevails, the study confirms that Middle PleistoceneMiddle PleistoceneGeological subperiod (about 770,000 to 126,000 years ago) marked by growing behavioural complexity among hominins.→ East Asia was a complex world in which several human forms lived side by side, met and interbred. Homo erectus, the Denisovans and perhaps other populations still unknown shared the same territories for hundreds of thousands of years.

Human history looks less and less like a tree with neatly separated branches and more and more like a bush whose twigs cross and rejoin. And thanks to a few teeth, tiny time capsules, we are beginning to read the traces of these encounters, written in the proteins of our distant cousins and sometimes, discreetly, in our own.