Molecular mechanisms and genetic architecture of sexual attractiveness.

描述（由申请人提供）： 是什么让个人有吸引力，为什么我们会有这样的偏好？性吸引力的有效指标必须诚实地反映个人的健康和生殖潜力，因此，必须在分子水平上与它们所代表的关键健康参数相联系。然而，很少有研究已经确定了特定的分子关系，将有吸引力的性状与影响生殖健康的途径联系起来。我们的初步数据确定：（i）衰老和胰岛素信号传导途径都调节果蝇中特定化学信息素的产生（a.ka.，表皮的碳氢化合物）通过转录调控参与碳氢化合物合成的关键酶，（ii）这些变化导致动物性吸引力的改变，（iii）这些影响的机制也可能涉及第二个营养感应途径，TOR途径。基于这些数据，我们假设，某些有吸引力的性状可能代表明显的分子途径，是决定健身的关键延伸。我们将检验这一假设，通过解剖的直接分子之间的联系，胰岛素信号和TOR活动，信息素成分，生殖功能，果蝇的性吸引力。我们还将研究这些联系对自然种群遗传变异的影响。这项工作很重要，因为了解从基因型到吸引力的分子联系，以及作用于它们的选择力，将为更详细地分析配偶选择的进化打开大门，并为深入了解驱动性状进化的生理约束机制提供帮助。我们的方法是创新的，因为它结合了有针对性的遗传操作与行为措施，以确定配偶质量，营养感和性吸引力之间联系的分子基础。然后，我们会问这些机制是否也可以解释自然变异。换句话说，我们将能够评估我们在实验室中发现的与该领域相关的程度。我们的研究将进一步加深我们对两种重要营养素的理解， 这些传感通路与许多人类疾病有关，包括癌症、糖尿病和心脏病。此外，这些研究可能揭示代谢途径的分子特征，可用作疾病早期诊断的指标，它们可能预示着通过化学传感方法进行准确和廉价的疾病早期检测的发展。

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.