400,000-Year-Old Tooth Proteins Link Homo Erectus to Denisovans and Leave a Trace in Modern Humans

Overview

A team led by paleoanthropologist Qiaomei Fu of the Institute of Vertebrate Paleontology and Paleoanthropology at the Chinese Academy of Sciences has extracted proteins from six Homo erectus teeth unearthed at three archaeological sites in China, revealing a molecular signature shared with Denisovans that persists today in some living populations. The study, published in Nature on May 13, 2026, represents one of the first times ancient proteins have been used to trace potential gene flow between H. erectus and another archaic human lineage.

What We Know

The six teeth came from three well-known Chinese fossil sites: Zhoukoudian near Beijing — the location that produced the original “Peking Man” fossils in the early twentieth century — along with Hexian in Anhui Province and Sunjiadong in Henan Province, according to Archaeology Magazine. All specimens date to approximately 400,000 years ago, placing them in the Middle Pleistocene.

Using micro-destructive acid etching to preserve the physical structure of the teeth, the researchers extracted 11 different enamel proteins and examined hundreds of amino acid positions within them, as reported by Live Science. The team also developed a technique for determining the biological sex of fossil specimens using the AMELY protein, according to phys.org.

The analysis produced two notable findings. The first is an amino acid variant designated AMBN-A253G, present in all six specimens but not found in any other known human lineage, living or extinct, according to Archaeology Magazine. Its presence across all three geographically separated sites suggests the fossils belong to a single interconnected population rather than isolated groups.

The second finding is more consequential for understanding human prehistory. A second variant, designated AMBN-M273V, was found in all six specimens and had previously been identified only in Denisovans, according to Archaeology Magazine. According to ScienceAlert, the researchers propose that the variant may have originated in populations related to H. erectus, then passed into Denisovans, and ultimately ended up in the genomes of some modern humans through Denisovan interbreeding with H. sapiens.

That modern trace is measurable. According to The Conversation, the AMBN-M273V variant appears at a frequency of approximately 21 percent in the Philippines and around 1 percent in India — a distribution consistent with inheritance through Denisovan ancestry, since Denisovans are known to have contributed genetic material to the ancestors of modern Southeast Asian and Oceanian populations.

The paper’s statement that “their shared habitats create opportunities for interactions,” as cited by ScienceAlert, frames the protein evidence as consistent with geographic coexistence and plausible interbreeding between H. erectus and early Denisovan populations in East Asia.

John Hawks, an anthropologist at the University of Wisconsin–Madison who was not involved in the study, told Scientific American that the findings were striking: “It’s like, wow. The data just had to line up exactly right for this to happen.”

Why Enamel Proteins

DNA degrades over time, and recovering usable genetic material from specimens older than a few hundred thousand years is extremely difficult outside of exceptionally cold and dry environments. Dental enamel, however, is the hardest tissue in the human body, and its proteins survive long after DNA has degraded beyond recovery, according to The Conversation. The field of paleoproteomics — analyzing ancient proteins rather than ancient DNA — has been steadily expanding the temporal range over which researchers can draw biological inferences about extinct species.

Homo erectus represents a particularly important gap in the molecular record. The species spread out of Africa approximately 1.8 million years ago and survived until roughly 108,000 years ago, according to Live Science. Despite being one of the most successful and long-lived members of the human genus, its genetic relationships to other archaic lineages have remained largely opaque because its fossils predate recoverable DNA.

What We Don’t Know

The study does not establish direct DNA evidence of interbreeding between H. erectus and Denisovans — protein sequences carry less information than genome sequences and cannot determine the timing or frequency of any genetic exchange. The researchers’ reconstruction of a gene-flow pathway from H. erectus to Denisovans to modern humans is a hypothesis consistent with the protein data, not a conclusion that rules out alternative explanations.

It also remains unclear whether the AMBN-M273V variant confers any functional difference in tooth enamel structure or development, or whether it spread through populations purely by neutral drift. The AMBN-A253G variant, unique to the East Asian H. erectus specimens, raises the question of what other molecular differences distinguished these populations from their African and European counterparts — a question that cannot yet be answered with the available data.

Additional specimens from a wider geographic range and time period would be needed to map the full distribution of these variants and better constrain when and where population contact occurred.

Analysis

The study adds to a growing body of evidence that archaic human lineages — H. sapiens, Neanderthals, Denisovans, and now potentially H. erectus — were not reproductively isolated from one another whenever and wherever their ranges overlapped. Ancient DNA research has already demonstrated that modern humans carry Neanderthal and Denisovan ancestry; the new protein evidence extends the chain one step further back, to a lineage too old for DNA recovery.

Sally Christine Reynolds, Associate Professor in Hominin Palaeoecology at Bournemouth University, who wrote a commentary on the study for The Conversation, summarized the broader implication: rather than a branching tree, human evolution increasingly resembles a braided river, with lineages converging and diverging across time and geography.

The methodological contribution may ultimately prove as significant as the specific findings. If enamel proteins can routinely be extracted from fossils in this age range — and if those proteins carry enough sequence variation to track population relationships — paleoproteomics could provide a molecular window into parts of human prehistory that have been accessible only through anatomy and stone tools.