The taste of ribonucleosides: Novel macronutrients essential for larval growth are sensed by Drosophila gustatory receptor proteins

Animals employ various types of taste receptors to identify and discriminate between different nutritious food chemicals. These macronutrients are thought to fall into 3 major groups: carbohydrates/sugars, proteins/amino acids, and fats. Here, we report that Drosophila larvae exhibit a novel appetitive feeding behavior towards ribose, ribonucleosides, and RNA. We identified members of the gustatory receptor (Gr) subfamily 28 (Gr28), expressed in both external and internal chemosensory neurons as molecular receptors necessary for cellular and appetitive behavioral responses to ribonucleosides and RNA. Specifically, behavioral preference assays show that larvae are strongly attracted to ribose- or RNA-containing agarose in a Gr28-dependent manner. Moreover, Ca2+ imaging experiments reveal that Gr28a-expressing taste neurons are activated by ribose, RNA and some ribonucleosides and that these responses can be conveyed to Gr43aGAL4 fructose-sensing neurons by expressing single members of the Gr28 gene family. Lastly, we establish a critical role in behavioral fitness for the Gr28 genes by showing that Gr28 mutant larvae exhibit low survival rates when challenged to find ribonucleosides in food. Together, our work identifies a novel taste modality dedicated to the detection of RNA and ribonucleosides, nutrients that are essential for survival during the accelerated growth phase of Drosophila larvae.

Author summary Insects that undergo complete metamorphosis grow only during the larval stage of development. In many species, this period is restricted to a few days, during which larvae might increase their weight up to several hundred-fold. Drosophila melanogaster, for example, grow from a tiny first-instar larva of about 10 μg to a wandering third-instar larva weighing about 2 mg over a period of only 4.5 days. The main macronutrients known to be critical for this period of rapid growth are amino acids and sugars. In this study, we identify ribonucleosides and RNA as a new, additional type of nutrient necessary for rapid larval growth and survival. We show that larvae harbor taste neurons that express taste receptors necessary for sensing ribonucleosides and RNA. Larvae lacking these taste receptors show high mortality rates when exposed to a complex food environment that requires the location of ribonucleoside-containing food. We hypothesize that the ability to taste RNA evolved as a new taste modality in larvae of insects that go through a rapid growth period because ingestion of ribonucleosides, as opposed to de novo synthesis, provides a survival advantage during a period of extreme growth.