Ancestral receptor plays a key role in host detection by malaria-carrying mosquitoes

Malaria is caused by protozoan Plasmodium spp. parasites — transmitted by blood-feeding anopheline mosquitoes. Host-seeking by mosquitoes (and other pathogen-spreading insects) relies on the detection of host-associated cues [e.g. carbon dioxide (CO2), odors, and body heat; see especially the diagram in the attached editorial]. Receptors for CO2 and host odors have been characterized in mosquitoes; however, receptors that mediate, or serve to promote, heat-seeking and heat-induced blood feeding — have remained elusive. This topic is a perfect fit for the theme of GEITP, i.e. gene-environment interactions. The environmental signal is “heat” in the host; genetic networks in the mosquito participate in detecting that signal, and helping the insect “to close in for the kill” (er, uh, ‘the bite’).

Because vector mosquitoes are evolutionary descendants of non–blood-feeding ancestors, it remains unknown whether emergence of heat-seeking and warming-induced blood-feeding in mosquitoes — involves “generating novel thermoreceptors”, or “repurposing of existing thermoreceptors.” [As a fervent fan of divergent evolution, these GEITP pages heavily favor the latter hypothesis.] To date, mosquito orthologs of two fruit fly (Drosophila) warmth receptors, TRPA1 and GR28b, have been tested as candidate heat-seeking

receptors in the yellow fever mosquito Aedes aegypti, but neither was found to be responsible for heat-seeking in Aedes.

Although efforts have focused on warmth receptors, insects also possess “cooling-activated” receptors, which might be equally capable of supporting heat-seeking via “cooling-mediated repulsion”. In Drosophila, cooling detection is known to be mediated by IR21a, IR25a, and IR93a — three members of the ionotropic receptor (IR) family, a group of invertebrate-specific sensory receptors related to ionotropic glutamate receptors. IR21a is specifically required for cooling detection in the fruit fly and can confer cooling sensitivity when ectopically expressed (i.e. expressed in a cell-type, tissue-type, or developmental stage in which the gene is not usually expressed), whereas IR25a and IR93a are more broadly acting co-receptors that support cooling detection and other IR-dependent sensory modalities. At the behavioral level in Drosophila — IR21a, IR25a, and IR93a help the fly achieve optimal body temperatures by supporting avoidance of excessively cool, as well as excessively warm, temperatures.

Authors [see attached article & editorial) identified IR21a — a receptor evolutionarily conserved throughout insects — as an important mediator of heat-seeking in Anopheles gambiae. Although Ir21a mediates heat-avoidance in the Diptera, Drosophila, authors demonstrated that Ir21a drives heat-seeking, and heat-stimulated blood-feeding, in Anopheles. At a cellular level, Ir21a is essential for detection of cooling, suggesting that, during evolution, mosquito heat-seeking relied on cooling-mediated repulsion. These findings indicate that evolution of blood-feeding in Anopheles involves adaptation of an ancestral thermoreceptor from non–blood-feeding Diptera to serve a different purpose, i.e. a different function, in the mosquito. 😊


Science 7 Feb 2020; 367: 681-684 & editorial pp 628-629

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