Of ELIC and evolution

This month's installment of Generally Physiological considers an odorant receptor evolutionarily linked to mos­ quito preference for humans, the evolution of voltage­gated Ca 2+ and Na + channels, and the first single­ channel kinetic analysis of the bac­ terial pentameric ligand­gated ion channel ELIC. Remarkable as it might seem to any­ one trying to enjoy a summer eve­ ning outdoors, only 100 of the 1 to 10 million insect species with which we share the earth preferentially feed on human blood. Among those in­ sects that do, the mosquito Aedes ae-gypti is notorious as a vector for such diseases as dengue and yellow fever. In coastal regions of Kenya, an an­ cestral forest­dwelling subspecies, Ae. aegypti formosus, prefers to feed on nonhuman animals and coex­ ists with a " domestic " form, Ae. ae-gypti aegypti, that prefers people and invades their homes. McBride et al. (2014) established laboratory colonies of either " domestic " or " forest " sub­ species, which can be distinguished morphologically, and confirmed that these morphological differences cor­ related with preference for human or nonhuman hosts. Analysis of antennal genes identified 14 genes differen­ tially expressed in the same direction in human­preferring versus guinea pig–preferring mosquito colonies and F2 hybrids; two of these differentially expressed genes, both up­regulated in human­preferring mosquitoes, en­ coded odorant receptors (Or4 and Or103). When heterologously ex­ pressed in Drosophila olfactory neu­ rons, Or4 (the second most highly expressed ligand­selective OR in the antennae of domestic females) con­ ferred sensitivity to sulcatone, a vola­ tile component of human body odor that is less abundant in nonhuman species. Seven major alleles of Or4 were identified that encoded recep­ tors with varying sensitivity to sulca­ tone, with preference for humans linked to both high Or4 expression and high ligand sensitivity, leading the authors to propose that increased behavioral sensitivity to sulcatone may help mosquitoes distinguish hu­ mans from other animals. Which came first, the channel or its selectivity? The pore­forming subunits of eukary­ otic voltage­gated Ca 2+ (Ca v) and Na + (Na v) channels comprise four ho­ mologous domains (DI to DIV) that function as a pseudotetramer. Indi­ vidual Ca v and Na v channel domains resemble the single domains of volt­ age­gated K + channels, which func­ tion as tetramers, suggesting that four­domain channels may have evolved from single­domain channels through consecutive rounds of intra­ genic duplication. Noting that two­ pore channels …