Non-Canonical Odor Coding Ensures Robust Mosquito Attraction to Humans

Aedes aegypti mosquitoes spread deadly diseases, including dengue, Zika, yellow fever, and chikungunya. Only female mosquitoes bite, and they do so because they require a blood-meal for reproduction. Aedes aegypti prefer to bite human hosts, which contributes to their effectiveness as a deadly disease vector. Mosquitoes rely heavily on chemosensory cues, including carbon dioxide (CO2) emitted from breath and human body odor, which is a mixture of more than 200 different individual odorants. Although the exact odor profile of people varies considerably, Aedes aegypti are incredibly reliable in finding humans to bite, despite widespread efforts to by humans to mask our odor. Even mosquitoes with genetic mutations that eliminate entire families of chemosensory receptors are still able to find and bite humans. It remains unknown how the mosquito olfactory system is seemingly infallible in its ability to detect humans for taking a blood meal. In the well-studied olfactory systems of Drosophila melanogaster and Mus musculus, individual olfactory sensory neurons express a single type of olfactory receptor and project their axons to discrete regions, called glomeruli, in the antennal lobe or olfactory bulb, respectively. This organization is believed to be a widespread motif in olfactory systems and has been established dogma since the mid-2000s and is hypothesized to permit the brain to parse which subpopulation of olfactory neurons is activated by a given odor. To understand how human odor is encoded in the mosquito olfactory system, we developed a CRISPR-Cas9-based genetic knock-in strategy in Aedes aegypti and generated a suite of transgenic mosquito strains that label populations of olfactory sensory neurons. Surprisingly, we find that the olfactory system of Aedes aegypti does not have the expected “one-receptor-to-one-neuron-to-oneglomerulus” organization seen in other insects. Rather, there are many more receptors than glomeruli. We frequently observe co-expression of multiple chemosensory receptors within individual olfactory sensory neurons and individual glomeruli are commonly innervated by olfactory sensory neurons expressing different receptors. What is the functional consequence of this unconventional organization? To understand how co-expression of multiple chemosensory families affects human odor detection by mosquitoes, we examined a minimal mixture that drives host seeking behavior. Mosquitoes are attracted to the combination of the two human-derived, cues CO2 and lactic acid. We found that the same neurons that sense CO2 also sense volatile amines, including triethyl amine. These amines are detected by separate chemosensory receptor genes and we discovered that these cues can be interchanged to drive attraction in the presence of lactic acid. This sensory organization, in which multiple receptors that respond to very different types of chemicals are co-expressed, suggests a redundancy in the odor code at the level of the olfactory sensory neurons for cues that signal the presence of a human to bite. We speculate that this design supports the robust human host-seeking seen in this olfactory specialist

Non-canonical odor coding in the mosquito

Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor cod-ing. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demon-strates that the broad ligand-sensitivity of mosquito olfactory neurons depends on this non-canonical co-expression. The redundancy afforded by an olfactory system in which neurons co-express multiple chemosensory receptors may increase the robustness of the mosquito olfactory system and explain our long-standing inability to disrupt the detection of humans by mosquitoes

Improved reference genome of Aedes aegypti informs arbovirus vector control

Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector

Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control

Female Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, has been slowed by the lack of a high-quality genome assembly. Here we combine diverse genome technologies to produce AaegL5, a dramatically improved and annotated assembly, and demonstrate how it accelerates mosquito science and control. We anchored the physical and cytogenetic maps, resolved the size and composition of the elusive sex-determining M locus, significantly increased the known members of the glutathione-S-transferase genes important for insecticide resistance, and doubled the number of chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites. Using high-resolution QTL and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. We predict that AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly arboviral vector