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Did Early Humans Smell the World Like Denisovans and Neanderthals?

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It sounds a little like Stone Age standup: A Denisovan and a human walk past a bees’ nest heavy with honeycomb. What happens next?

According to a study led by University of Alaska Fairbanks biological anthropologist Kara C. Hoover and Universite Paris-Saclay biochemist Claire de March, the Denisovan, with the species’ greater sensitivity to sweet smells, may have immediately homed in on the scent and beat the human to a high-energy meal.

"This research has allowed us to draw some larger conclusions about the sense of smell in our closest genetic relatives and understand the role that smell played in adapting to new environments and foods during our migrations out of Africa,” said Hoover, a professor in the Department of Anthropology at UAF.

A paper on the research, recently published in iScience, was written by collaborators from UAF, Duke University, Universite Paris-Saclay, Tokyo University of Agriculture and Technology, and the University of Manchester. The study investigated whether humans share a sense of smell with their now-extinct Denisovan and Neanderthal cousins, who left Africa about 750,000 years ago. Contemporary humans left Africa about 65,000 years ago.

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To recreate the noses of our extinct genetic relatives and compare them to those of present-day people, the research team used publicly available genome sequences from multiple Neanderthals, one Denisovan and one ancient human. They used data from the 1000 Genomes project to represent modern humans.

They then compared 30 olfactory receptor genes from each group. The team found that 11 of the receptors had some novel mutations present only in extinct lineages. In the largest study of its kind to date, the team created laboratory versions of those 11 olfactory receptors and then exposed them to hundreds of odors at different concentrations. 

When the receptors detected an odor, they literally lit up. The speed and brightness of the luminescence told the scientists whether, how soon and to what degree each “nose” could smell the odors. While the receptors could detect the same things as modern humans, they differed in sensitivity to many of the odors.

“We literally reproduced an event that hadn’t happened since the extinction of Denisova and Neanderthal 30,000 years ago: an extinct odorant receptor responding to an odor in cells on a lab bench,” de March said. “This took us closer to understanding how Neanderthal and Denisova perceived and interacted with their olfactory environment.”

Neanderthals, who lived in Eurasia between 430,000 and 40,000 years ago, had the poorest sense of smell. For example, the Neanderthal from the Chagyrskaya Cave couldn’t detect the sex steroid androstadienone, which smells something like sweat and urine. That may have been useful, Hoover said, given that they were trapped in close quarters in caves during glacial maximums, when the ice sheets from the poles expanded southward and made many areas uninhabitable.

Denisovans have left behind less physical evidence than Neanderthals. They are known mostly from modern-day Siberia, where remains in the Denisova Cave were dated to between 76,200 and 51,600 years ago. Denisovans were generally more sensitive to odors than humans and much more sensitive than Neanderthals. They were most responsive to sweet and spicy smells like honey, vanilla, cloves and herbs. That trait could have helped them find high-calorie food.

Present-day humans fell somewhere in the middle.

“This is the most exciting research I have ever been involved in,” said co-author Matthew Cobb from the University of Manchester. “It shows how we can use genetics to peer back into the sensory world of our long-lost relatives, giving us insight into how they will have perceived their environment and, perhaps, how they were able to survive.”

In many species, olfactory receptors have been linked to their ecological and dietary needs.

"Each species must evolve olfactory receptors to maximize their fitness for finding food," said co-author Hiroaki Matsunami in a Duke University news release. "In humans, it's more complicated because we eat a lot of things. We're not really specialized."

Smell is integral to the human story, Hoover said. “Such a strongly overlapping olfactory repertoire suggests that our generalist approach to smelling has enabled us to find new foods when migrating to new places — not just us but our cousins who left Africa much earlier than us!”

Reference: March CA de, Matsunami H, Abe M, Cobb M, Hoover KC. Genetic and functional odorant receptor variation in the Homo lineage. iScience. 2023;26(1). doi: 10.1016/j.isci.2022.105908

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