Protein remnants in fossil enamel reveal new ways to study evolution. These molecules stretch our view of molecular preservation far into the past.
Proteins naturally break down over time, which makes it difficult to trace their origins and preserve their biological history. However, a recent study has revealed the presence of ancient proteins preserved in the enamel of 18-million-year-old fossilized mammal teeth from Kenya’s Rift Valley, offering new insights into how these animals lived and evolved.
In their newly published paper in Nature, researchers from Harvard University and the Smithsonian Museum Conservation Institute detail their discovery. “Teeth are rocks in our mouths,” said Daniel Green, field program director in the Department of Human Evolutionary Biology and lead author of the study. “They’re the hardest structures that any animals make, so you can find a tooth that is a hundred or a hundred million years old, and it will contain a geochemical record of the life of the animal.” This includes information about the animal’s diet, water sources, and surrounding environment.
“In the past, we thought that mature enamel, the hardest part of teeth, should really have very few proteins in it at all,” said Green. However, utilizing a newer proteomics technique called liquid chromatography tandem mass spectrometry (LC-MS/MS), the team was able to detect a “a great diversity of proteins… in different biological tissues.”
“The technique involves several stages where peptides are separated based on their size or chemistry so that they can be sequentially analyzed at higher resolutions than was possible with previous methods,” explained Kevin T. Uno, associate professor in HEB and one of the paper’s corresponding authors.
“We and other scholars recently found that there are dozens – if not even hundreds – of different kinds of proteins present inside tooth enamel,” said Green.
Elephants and rhinos offer thick enamel samples
After confirming that modern teeth contain a wide variety of proteins, the researchers turned their attention to fossils. They partnered with the Smithsonian and the National Museum of Kenya to examine fossilized teeth, focusing on early elephants and rhinoceroses. As plant-eating mammals, these animals had large teeth adapted for grinding vegetation. “They can have enamel two to three millimeters thick,” said Green. “It was a lot of material to work with.”
Their analysis revealed peptide fragments—short chains of amino acids that form proteins—preserved in these fossils for as long as 18 million years.
Green described the discovery as “field-changing.” “Nobody’s ever found peptide fragments that are this old before,” he said, adding that the results were “kind of shocking.” Prior to this study, the oldest known peptide sequences came from materials around three and a half million years old. “With the help of our colleague Tim Cleland, a superb paleoproteomicist at the Smithsonian, we’re pushing back the age of peptide fragments by five or six times what was known before.”
The peptides identified represent a variety of proteins involved in different biological roles, collectively referred to as the proteome, Green explained.
“One of the reasons that we’re excited about these ancient teeth is that we don’t have the full proteome of all proteins that could have been found inside the bodies of these ancient elephants or rhinoceros, but we do have a group of them.” He added, “there might be more information available from a group of them than just one protein by itself.”
New potential in paleobiology and evolution
This research “opens new frontiers in paleobiology, allowing scientists to go beyond bones and morphology to reconstruct the molecular and physiological traits of extinct animals and hominins,” said Emmanuel K. Ndiema, senior research scientist at the National Museum of Kenya, and paper coauthor. “This provides direct evidence of evolutionary relationships. Combined with other characteristics of teeth, we can infer dietary adaptations, disease profiles, and even age at death – insights that were previously inaccessible.”
In addition to shedding light on the lives of these creatures, it helps place them in history. Uno elaborated: “We can use these peptide fragments to explore the relationships between ancient animals, similar to how modern DNA in humans is used to identify how people are related to one another.”
“Even if an animal is completely extinct – and we have some animals that we analyze in our study who have no living descendants – you can still, in theory, extract proteins from their teeth and try to place them on a phylogenetic tree,” said Green. Such information “might be able to resolve longstanding debates between paleontologists about what other mammalian lineages these animals are related to using molecular evidence.”
Although this research began as “a small side project” of a much larger project involving dozens of institutions and researchers from around the world, said Green, “we were surprised at just how much we found. There really are a lot of proteins preserved in these teeth.”
Reference: “Eighteen million years of diverse enamel proteomes from the East African Rift” by Daniel R. Green, Kevin T. Uno, Ellen R. Miller, Craig S. Feibel, Eipa Emmanuel Aoron, Catherine C. Beck, Aryeh Grossman, Francis M. Kirera, Martin M. Kirinya, Louise N. Leakey, Cynthia Liutkus-Pierce, Fredrick K. Manthi, Emmanuel K. Ndiema, Isaiah O. Nengo, Cyprian Nyete, John Rowan, Gabrielle A. Russo, William J. Sanders, Tara M. Smiley, Patricia Princehouse, Natasha S. Vitek and Timothy P. Cleland, 9 July 2025, Nature.
DOI: 10.1038/s41586-025-09040-9
This research was partially funded by the National Science Foundation and Smithsonian’s Museum Conservation Institute.
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1 Comment
No mention in the article that finding preserved proteins and peptide seauences seems to falsify, not support, the assumed age of the fossils? It seems counter to the scientific method to assume that a hypothesis/assigned age is true *regardless* of the data, let alone to assume it’s so incontrovertibly true that finding data that would otherwise falsify the long ages means that the scientists can be sure that some unknown mechanism of preserving soft tissue and proteins for millions of years must definitely exist.
Even by the most generous and special pleading proposed methods that peptide sequences might be preserved longer than formerly thought in fossils, none have managed to get passed a few hundred thousand years. That’s a pretty significant problem to avoid mentioning at all in an article about intact peptide sequences being found intact in an allegedly 18 million year old fossil.