“These hummingbirds look mad,” said a statement about the research, published Thursday in the journal Science.

The paper explores how hummingbirds evolved to prefer nectar when other birds lack the ability to perceive sweetness. Since they diverged from their closest relative, the swift, 40 million to 72 million years ago, hummingbirds have used their rare avian sweet tooth – and a taste for bugs – to expand to 300 species in South and North America.

It took an international team of scientists led by Harvard University biologist Maude W. Baldwin more than three years to answer that question. Baldwin reached out to Stephen Liberles at the Department of Cell Biology at Harvard’s medical school, and they started researching how hummingbirds developed a taste receptor that wasn’t present in the genome of other birds. Eventually they turned to Yasuka Toda, a graduate student at the University of Tokyo, who developed a way to test taste receptors in cell culture.

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The research is important because “sensory systems give us a window into the brain to define what we understand about the world around us,” Liberles said. “The taste system is arguably a really direct line to pleasure and aversion, reward and punishment, sweet and bitter. Understanding how neural circuits can encode these …gives us a window into other aspects of perception.”

Before genes were sequenced and studied, scientists assumed what everyone else did: chickens responded to sugar, salt, sourness and bitterness the way mammals do, with sensory functions that recognize savory flavors. Later research showed that chickens had no sweet-taste receptor gene.

“The immediate question to ornithologists or to anybody who has a birdfeeder in the backyard was: What about hummingbirds?” Baldwin, who’s visiting Tokyo, said in a statement that explained the research. “If they are missing the single sweet receptor, how are they detecting sugar?”

Baldwin, the paper’s first co-author, worked to clone genes for taste receptors from chickens, swifts and hummingbirds to test how the responded to amino acids and proteins to detect sugars. Toda, another first co-author, mixed chicken and hummingbird taste receptors to see how their functions changed over time. Those are two reasons why the project took so long.

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Toda discovered that hummingbirds somehow developed 19 mutations over the eons since they diverged from their closest relatives among birds.

“Together they showed that in chickens and swifts, the receptor responds strongly to amino acids,” but hummingbirds responded to them weakly, the paper said. Hummingbirds reacted strongly to the sweet stuff, carbohydrates.

It is the first time a receptor has been shown to react to carbs, Baldwin said.

“If you look at the structure of the receptor, it involved really dramatic changes over its entire surface to accomplish this complex feat,” Liberies said in the statement. “This dramatic change in the evolution of a new behavior is a really powerful example of how you can explain evolution on a molecular level.”

They tested their theories outside the lab in the Santa Monica Mountains, where hummingbirds frequent outside Los Angeles, and on the banks of the Charles River in Boston. That’s where the birdfeeders and cameras were set up.

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Researchers seduced them with sugars full of nectar – glucose, fructose and sucrose, among others. Then they pulled a switch, substituting water and other flavors, such as synthetic sweeteners that flavor soft drinks, then tested how long the birds fed.

The research said Anna Hummingbirds slurped at natural sugars and artificial sweeteners for longer periods, but were averse to synthetic sugars. And they wanted nothing to do with water.