Molecular mechanisms and genetic architecture of sexual attractiveness.

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DESCRIPTION (provided by applicant): What makes individuals attractive and why do we have the preferences that we do? Effective indicators of sexual attractiveness must be an honest reflection of an individual's health and reproductive potential and as such, must be linked at the molecular level to the key fitness parameters that they represent. However, very few studies have identified specific molecular relationships that link attractive traits to the pathways that influence reproductive fitness. Our preliminary data establish that: (i) both aging and the insulin signaling pathway modulate the production of specific chemical pheromones in Drosophila (a.ka., cuticular hydrocarbons) through transcriptional regulation of key enzymes involved in hydrocarbon synthesis, (ii) that these changes cause alterations in animal sexual attractiveness, and (iii) mechanisms underlying these effects may also involve a second nutrient-sensing pathway, the TOR pathway. Based on these data, we hypothesize that certain attractive traits may represent conspicuous extensions of molecular pathways that are critical for determining fitness. We will test this hypothesis by dissecting the immediate molecular links between insulin signaling and TOR activity, pheromone composition, reproductive function, and sexual attractiveness in Drosophila. We will also investigate the impact of these links on genetic variation in natural populations. This work is important because an understanding of molecular links leading from genotype to attractiveness, and the selective forces acting on them, would open the door for a more detailed analysis of the evolution of mate choice and provide insight into mechanisms underlying the physiological constraints that drive trait evolution. Our approach is innovative because it combines targeted genetic manipulations with measures of behavior to identify molecular underpinnings of links between mate quality, nutrient-sensing, and sexual attractiveness. We will then ask whether these mechanisms can also account for natural variation. In other words, we will be able to assess the extent to which what we discover in the lab is relevant in the field. Our research will further our understanding of two important nutrient sensing pathways that are implicated in many human illnesses, including cancer, diabetes and heart disease. Furthermore, these studies may reveal molecular signatures of metabolic pathways that can be used as indicators in early diagnosis of disease, and they may foreshadow the development of accurate and cheap early detection of disease by chemosensory methods.