To nourish their eggs, bloodsucking female mosquitoes have become major vectors of human disease. And what’s more, some of them actually prefer to bite people. A “domestic” form of the yellow fever mosquito breeds indoors in water jugs and has evolved to specialize in hunting humans -- spreading dengue, yellow fever, and chikungunya. But along the coast of Kenya, this domestic form (Aedes aegypti aegypti) coexists with its ancestral, “forest” form (Aedes aegypti formosus), which lays its eggs outdoors and prefers to bite other animals.
Now, researchers have identified the genetic tweak that explains why the deadly subspecies prefers to feed on humans: Their taste for our blood is sustained by the abundance and sensitivity of one odor-detecting gene in their antennae that make them more sensitive to our scent. The work, published in Nature this week, helps explain how a human-biting specialist evolved from its animal-loving ancestor.
“It was a really good evolutionary move,” says Leslie Vosshall from Rockefeller University in a university statement. “We provide the ideal lifestyle for mosquitoes. We always have water around for them to breed in, we are hairless, and we live in large groups.”
Vosshall and colleagues collected larvae of both forms from treeholes and from clay pots and metal cans using turkey basters and sieves in Rabai, Kenya. They grew colonies in the lab and documented the striking divergence in their preference for human versus non-human animal odor in a three-part experiment. And the differences were stark.
The team put both types in a large cage and offered them a guinea pig or a (lucky) researcher’s arm. They also got to choose between streams of air that had passed over guinea pigs or humans. And to rule out other mosquito attractants like exhaled carbon dioxide, the team allowed the mosquitoes to choose between the scent of nylon sleeves that had been worn by humans or guinea pigs. Although domestic mosquitoes would sometimes go for the guinea pig, it happened very rarely, Princeton’s Carolyn McBride says in a news release.
Aedes aegypti aegypti on the left, Aedes aegypti formosus on the right.
When the team interbred the two subspecies, and then interbred those offspring to create second-generation hybrids, they found 14 genes that were different between the human- and rodent-preferring skeeters. In particular, the preference for human odor is tightly linked to the odor receptor gene Or4, which showed higher levels of expression in the domestic mosquitoes’ antennae (the equivalent of our noses).
Then, human volunteers and guinea pigs donned pantyhose for 24 hours, after which these were placed in a machine to separate out scent into hundreds of chemicals. That’s how they discovered that Or4 is highly attuned to sulcatone, a prevalent compound in human odor. Additionally, when the team implanted the gene into fruit-fly neurons, the cells showed a burst of activity when exposed to sulcatone.
“They’ve acquired a love for human body odor,” Vosshall says. They retuned the way odors are detected by their antennae, moved indoors, and started breeding in clean water. McBride adds: "The more we know about the genes and compounds that help mosquitoes target us, the better chance we have of manipulating their response to our odor."
Images: Carolyn McBride, Department of Ecology and Evolutionary Biology and the Princeton Neuroscience Institute (top), Alex Wild (middle)