Growing Apart: Sex-Specific Plasticity And The Developmental Regulation Of Male And Female Body Size

在包括人类在内的许多动物物种中，成年雄性和雌性的体型不同。然而，尽管这种现象很普遍，但科学家们对导致雄性和雌性长到不同大小的机制知之甚少。先前的研究使用果蝇黑腹果蝇作为模式生物，表明两性之间体型的差异是由于雄性和雌性在生长过程中对营养的反应不同。在几乎所有的动物中，生长期间高水平的营养会增加成年动物的体型。初步数据显示，虽然在低质量的饮食中饲养的雄性和雌性体型相同，但雌性比雄性更能适应高质量的饮食，并且长得更大。因此，女性比男性对营养更敏感。本研究的目的是发现使雌性在生长和最终体型方面比雄性对营养更敏感的发育和生理机制。这项研究有助于加深对女性和男性如何以及为什么对环境刺激做出不同反应的理解，这一现象对包括人类生物学在内的许多生物学方面具有广泛而重要的影响。该赠款还将支持更广泛的影响活动，旨在将来自UIC校园和更广泛的芝加哥地区的学术，医学和教育工作者聚集在一起，讨论男女生物差异的科学，医学和社会影响。Shingleton实验室和其他人的研究表明，黑胃果蝇的性别尺寸二态性（SSD）至少部分受到胰岛素/ igf信号通路的调节，这是一种几乎所有动物的体型与营养相关的调节因子；这就是营养可塑性。这些数据，以及一些关于SSD进化的适应性假设，表明SSD和性别特异性可塑性（SSP）之间的关系，即一种性别的体型比另一种性别更容易受到环境的影响。Shingleton实验室的初步数据通过显示等基因果蝇谱系中SSD和SSP之间的强烈遗传相关性来支持这种关系。因此，本项目的目标是利用果蝇作为模型生物来验证这样的假设，即调节性SSD的发育遗传机制也调节SSP，并且这些机制要么靶向胰岛素信号通路，要么位于胰岛素信号通路内。该假设将通过以下方式得到验证：(1)利用全基因组关联研究来确定相同的基因座是否与SSD和SSP的遗传变异相关；(2)在基因表达/活性水平上表征雌性和雄性对发育营养变化的差异反应；(3)功能检测[1]和[2]基因在SSD和SSP调控中的作用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

In many animal species, including humans, adult males and females have different body sizes. However, despite the commonality of this phenomenon, scientists have a very poor understanding of the mechanisms that cause males and females to grow to different sizes. Previous research, using the fruit fly Drosophila melanogaster as a model organism, suggest that the difference in body size between sexes is due to differences in how males and females respond to nutrition during their growth. In almost all animals, high levels of nutrition during growth increase adult body size. Preliminary data show that while males and females are the same size when reared on a poor-quality diet, females are better able to respond to a high-quality diet than males, and grow to a larger size. Consequently, females are more nutritionally-sensitive than males. The goal of this study is to discover the developmental and physiological mechanisms that make females more nutritionally-sensitive than males with respect to their growth and final body size. This research contributes to a growing understanding of how and why females and males respond differently to environmental stimuli, a phenomenon that has wide-ranging and important implications for many aspects of biology, including human biology. The grant will also support broader impact activities designed to bring together academic, medical, and educational workers from across the UIC campus and wider Chicago-land area, to discuss the scientific, medical, and societal impacts of biological differences between females and males. Research by the Shingleton Laboratory and others indicate that sexual-size dimorphism (SSD) in Drosophila melanogaster is at least partially regulated by the insulin/IGF-signaling pathway, a regulator of body size with respect to nutrition in almost all animals; that is, nutritional plasticity. These data, as well as several adaptive hypotheses on the evolution of SSD, suggest a relationship between SSD and sex-specific plasticity (SSP), the phenomenon whereby body size in one sex is more environmentally variable than in the other sex. Preliminary data from the Shingleton Laboratory support such a relationship by showing a strong genetic correlation between SSD and SSP among isogenic Drosophila lineages. The goal of this project is therefore to use Drosophila melanogaster as a model organism to test the hypothesis that the developmental genetic mechanisms that regulate sexual SSD also regulate SSP, and that these mechanisms either target or lie within the insulin-signaling pathway. The hypothesis will be tested by: (1) using a genome-wide association study to determine whether the same loci are associated with genetic variation in SSD and SSP; (2) characterizing at the level of gene expression/activity how females and males differentially respond to changes in developmental nutrition, and; (3) functionally testing the role that genes (identified in [1] and [2]) play in regulating SSD and SSP.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.