Sexually attractive traits as activity indicators of nutrient-sensing pathways. Tatyana Y Fedina1, Tsung-Han Kuo2, Ingrid Hansen2, Klaus Dreisewerd3, Herman A Dierick2, Joanne Y Yew4, Scott D Pletcher1,2. 1) University of Michigan, USA; 2) Baylor College of Medicine, USA; 3) University of Münster, Germany; 4) National University of Singapore, Singapore.

   Purpose: Sexually attractive traits are thought to reflect an individuals health and reproductive potential, but the underlying molecular mechanisms through which they do so are generally unknown. Insulin/insulin-like growth factor signaling (IIS) is a systemic nutrient sensor known to modulate aging and reproduction across species. Here we investigate IIS effects on sexual attractiveness of D. melanogaster female cuticular hydrocarbons (CHCs). Methods: We used chico, dfoxo mutants, chico;dfoxo double mutants, and gsTub5>AktRNAi/Pten/InR/dFoxo/TORTED flies whose adults were exposed to RU486 to activate transgene expression. GC-MS and a novel mass-spec technique were used to obtain comprehensive CHC profiles. Male choice was quantified as a relative time spent courting one of the two decapitated females in two-choice attractiveness assay. Results: Genetic manipulations of IIS pathway consistently and predictably altered CHC profiles and the expression of CHC synthesis enzymes (eloF, desat1, desat2, desatF); this effect was independent of dFOXO and involved the nutrient-sensing Target-of-Rapamycin pathway. Manipulations that reduced IIS also reduced attractiveness, while females with increased IIS were more attractive to males. Decreased IIS shifted CHC composition to favor long-chain compounds. Conclusions: D.m. female IIS pathway activity is reflected in CHC composition that is used by males to choose females with increased IIS (=high immediate fecundity). This is the first study to dissect the link between the activity of a conserved nutrient sensing pathway in the adult and sexual attractiveness. We further hypothesize that different attractiveness traits across species may represent the activity of a few conserved molecular regulators of growth and reproduction. In support of this hypothesis, subsequent studies in rhinoceros beetles have shown that IIS activity during larval development can be reflected in adult ornaments.