For the first time, scientists have analyzed metabolism-related molecules from fossilized bones of animals that lived between 1.3 and 3 million years ago. This research provides new insights into the animals’ health, diets, and the environments in which they lived. The findings, published in Nature, indicate that these ancient environments were warmer and wetter than those found today.
Metabolites are molecules produced during digestion and other chemical processes in the body. They can reveal information about health, disease, diet, and environmental exposures. While metabolomics is commonly used to study human diseases and drugs, its application to fossils has been limited compared to DNA analysis.
Timothy Bromage, professor of molecular pathobiology at NYU College of Dentistry and affiliated professor in NYU’s Department of Anthropology, led the study with an international team. “I’ve always had an interest in metabolism, including the metabolic rate of bone, and wanted to know if it would be possible to apply metabolomics to fossils to study early life. It turns out that bone, including fossilized bone, is filled with metabolites,” said Bromage.
Collagen preservation in ancient bones has previously been documented by paleontologists. Bromage noted: “I thought, if collagen is preserved in a fossil bone, then maybe other biomolecules are protected in the bone microenvironment as well.” He directs the Hard Tissue Research Unit at NYU College of Dentistry.
Bones have spongy surfaces surrounded by capillary networks that exchange oxygen and nutrients with the bloodstream. Bromage suspected that metabolites carried by blood could become trapped within bone during formation.
To test this idea, researchers used mass spectrometry on present-day mouse bones and identified nearly 2,200 metabolites for analysis. The same technology also detected proteins such as collagen in some samples.
The team then applied their methods to animal fossils from sites in Tanzania, Malawi, and South Africa—regions where early humans lived. Fossilized bone fragments from rodents (mouse, ground squirrel, gerbil), antelope, pig, and elephant were studied using these techniques.
Thousands of metabolites were identified in these ancient samples; many overlapped with those found in modern animals.
Some metabolites reflected normal biological functions like amino acid or carbohydrate metabolism. Others suggested genetic traits; for example, certain metabolites pointed to genes associated with estrogen—indicating some animals were female.
Evidence was also found of disease response: a 1.8-million-year-old ground squirrel from Olduvai Gorge showed signs of infection by Trypanosoma brucei—the parasite responsible for sleeping sickness—and displayed an anti-inflammatory response likely due to this infection. “What we discovered in the bone of the squirrel is a metabolite that is unique to the biology of that parasite, which releases the metabolite into the bloodstream of its host. We also saw the squirrel’s metabolomic anti-inflammatory response, presumably due to the parasite,” said Bromage.
Researchers could deduce aspects of diet by identifying plant-derived metabolites—including those from aloe and asparagus—within animal bones. “What that means is that, in the case of the squirrel, it nibbled on aloe and took those metabolites into its own bloodstream,” explained Bromage. “Because the environmental conditions of aloe are very specific, we now know more about the temperature, rainfall, soil conditions, and tree canopy—essentially reconstructing the squirrel’s environment. We can build a story around each of the animals.”
The reconstructed environments align with previous research indicating wetter and warmer conditions millions of years ago at sites like Olduvai Gorge—which ranged from freshwater woodland grassland to dry woodlands and marshes.
“Using metabolic analyses to study fossils may enable us to reconstruct the environment of the prehistoric world with a new level of detail—as though we were field ecologists in a natural environment today,” said Bromage.
Additional contributors included researchers from NYU College of Dentistry; NYU Grossman School of Medicine; institutions in France; Germany; Canada; Rutgers University (US); Eurofins Lancaster Laboratories (US); Université de Bordeaux (France). The Leakey Foundation supported this work along with additional support for analytical technology provided by grants from National Institutes of Health.
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