Researchers in New York and Boston report that mosquitos have evolved redundancies in their olfactory system to make sure they can always smell human scents. The findings help explain why knocking out an entire family of odor-sensing receptors from the mosquito genome failed to make humans undetectable.

In most animals, an olfactory neuron is only responsible for detecting one type of odor. “If you're a human and you lose a single odorant receptor, all of the neurons that express that receptor will lose the ability to smell that smell,” says Leslie Vosshall, of the Howard Hughes Medical Institute and a professor at Rockefeller University. 

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But Vosshall and her colleagues report in the journal Cell that this is not the case in mosquitoes.  “You need to work harder to break mosquitoes because getting rid of a single receptor has no effect,” says Vosshall. “Any future attempts to control mosquitoes by repellents or anything else has to take into account how unbreakable their attraction is to us.”

The project started unexpectedly while looking at how human odor was encoded in the mosquito brain. The team found that neurons stimulated by the human odor 1-octen-3-ol are also stimulated by amines, another type of chemical mosquitoes use to look for humans. This is unusual since according to all existing rules of how animals smell, neurons encode odor with narrow specificity, suggesting that 1-octen-3-ol neurons should not detect amines.  “Mosquitoes are breaking all of our favorite rules of how animals smell things,” says Margo Herre, a scientist at Rockefeller University.

Meg Younger, a professor at Boston University, adds that the neurons for detecting humans through 1-octen-3-ol and amine receptors were “surprisingly” not separate populations, which may allow all human-related odors to activate “the human-detecting part” of the mosquito brain even if some of the receptors are lost, acting as a fail-safe.

The team also utilized single-nucleus RNA sequencing to see what other receptors individual mosquito olfactory neurons are expressing. “The result gave us a broad view of just how common co-expression of receptors is in mosquitoes,” says Olivia Goldman, with the Laboratory of Neurogenetics and Behavior at Rockefeller.

Vosshall thinks that other insects may have a similar mechanism. Christopher Potter’s research group at Johns Hopkins University recently reported that fruit flies have similar co-expression of receptors in their neurons. “This may be a general strategy for insects that depend heavily on their sense of smell,” says Vosshall.

In the future, Younger’s group plans to uncover the functional significance of the co-expression of different types of olfactory receptors.