The yellow fever mosquito, Aedes aegypti, is one of the world’s deadliest mosquitoes. Found in tropical and subtropical areas worldwide, it is the principal carrier of yellow fever, dengue fever, and chikungunya. Yellow fever annually kills tens of thousands of people worldwide, primarily in Africa, while dengue fever infects hundreds of millions.
Interestingly, these mosquitoes did not always rely on human blood. Their ancestors fed on furrier animals in the forest, but then — thousands of years ago — some of these bloodsuckers made a smart switch: They began biting humans and hitchhiked all over the globe, spreading disease in their wake.
“It was a really good evolutionary move,” said Leslie B. Vosshall, the Robin Chemers Neustein Professor and head of the Laboratory of Neurogenetics and Behavior at the Rockefeller University. “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.”
In the 1960s and 1970s, scientists visiting Kenya observed two distinct yellowfever mosquito populations living just hundreds of meters apart. Black mosquitoes (Aedes aegypti formosus) tended to lay their eggs outdoors and preferred to bite forest animals. However, their light-brown cousins (Aedes aegypti aegypti) tended to breed indoors in water jugs and mostly hunted humans.
To understand the evolutionary basis of this attraction, Vosshall and her colleagues examined the genes that drive some mosquitoes to prefer humans. Their findings, published in Nature, suggest that human-loving mosquitoes are attracted to our scent.
“They’ve acquired a love for human body odor, and that’s a key step in specializing on us,” she said.
The researchers conducted a three-part series of experiments to establish the domestic yellowfever mosquito’s preference for human scent. Forest and domestic mosquitoes were put into a large cage and allowed to bite either a guinea pig or a researcher’s arm. Then the mosquitoes were allowed to choose between streams of air that had passed over a guinea pig or human arm. Finally, to rule out general mosquito attractants such as exhaled carbon dioxide, mosquitoes were allowed to choose between the scent of nylon sleeves that had been in contact with a human or a guinea pig.
In all three cases, the domestic form of the yellowfever mosquito showed a strong preference for human scent, while the forest form primarily chose the guinea pig. Although domestic mosquitoes would sometimes go for the guinea pig, it happened very rarely.
In addition, the researchers found that the yellowfever mosquito contains an odor-detecting gene (AaegOr4) in its antennae that is highly attuned to sulcatone, a compound prevalent in human odor, and that the AaegOr4 gene is more abundant and more sensitive in the human-preferring “domestic” form of the yellowfever mosquito than in its ancestral “forest” form, which prefers the blood of non-human animals.
“[AaegOr4] is very highly expressed in human-preferring mosquitoes,” Vosshall said.
The switch from preferring animals to humans involved a variety of behavior adjustments: Mosquitoes had to become comfortable living around humans, entering their homes, and breeding in clean water found in water jugs instead of the muddy water found in tree holes.
“There’s a whole suite of things that mosquitoes have to change about their lifestyle to live around humans,” Vosshall said. “This paper provides the first genetic insight into what happened thousands of years ago when some mosquitoes made this switch.”
The research may also aid in mosquito-control efforts in the future.
“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,” said first author Carolyn “Lindy” McBride, an assistant professor in Princeton University’s Department of Ecology and Evolutionary Biology.
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