Collaborative Research: How to get SMAL: Studying island dwarfism to find Shared Molecular mechanisms Across Life history traits

人类和动物的许多特征是复杂的，它们既由环境决定，也由许多基因决定；这些特征包括身体大小和生殖成熟年龄。在自然种群中决定这些复杂特征的分子机制还不是很清楚。这个项目的研究目标是了解调节复杂性状的机制，它们在自然种群中是如何改变的，以及这些机制的哪些方面在物种之间是共享的。这个项目使用了自然实验的力量，在这个实验中，被隔离在岛屿上的动物变小了，繁殖方式发生了变化，类似于选择性繁殖的动物，如狗、牛和鸡。该项目将对比加州大陆和加州海峡岛上五种爬行动物的种群，以了解它们的基因组、细胞和激素生理的变化，这些变化会改变它们在岛屿上的身体大小和繁殖。在这个过程中，将开发新的工具来研究爬行动物的遗传和激素生理学，这些工具可以用来了解自然和动物园种群的健康，以帮助保护工作和农业。该项目将吸引30多名本科生和研究生(横跨三所大学)和高中教师参与研究，并将支持基于科学研究的教学模块的开发。这项研究的发现将提高我们对基因和环境如何决定复杂特征的一般理解，更具体地说，将识别在自然群体中调节体型和繁殖的机制，这些机制在动物物种中是共享的。复杂的特征，如身体大小和繁殖，天生就受到分子网络的调节，而分子网络受到遗传和环境的影响，但复杂特征如何在自然种群中调节和共享的分子机制尚不清楚。解开这些分子机制将是我们理解复杂特征如何在生态不同的种群中受到调控的变革性的一步。生长激素胰岛素/胰岛素样信号转导网络(GH-IIS)在生物医学实验室模型和人工选择的物种中因其在生长、体型和生殖中的作用而被广泛研究，从而使其成为调节自然系统中这些复杂特征的理想候选网络。为了了解自然种群中复杂特征如何改变的机制基础，以及这些机制在物种中的共享程度，该项目将对比大陆和岛屿上的五种爬行动物物种，其中三种表现为岛状矮化，两种不表现为岛状矮化。数据将被整合在GH-IIS分子网络的多个生物组织水平上，以追求以下三个目标：(1)量化GH-IIS激素生理和自然种群生活史特征之间的关系；(2)评估GH-IIS网络中的遗传差异；以及(3)量化细胞生理和细胞内信号的差异。这个项目将进一步了解网络中的哪些节点对自然种群中的生态压力做出反应，哪些节点受到限制。这一新的知识跨越生物学的层级，以确定在自然种群中定义复杂特征的机械原理。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Many human and animal traits are complex such that they are defined by both the environment and many genes; such traits include body size and age of reproductive maturity. The molecular mechanisms that determine these complex traits in natural populations are not well understood. The research goal of this project is to understand the mechanisms regulating complex traits, how they are altered in natural populations, and what aspects of these mechanisms are shared across species. This project uses the power of a natural experiment where animals isolated on islands have become small with altered reproduction similar to animals under selective breeding, such as dogs, cattle, and chickens. This project will contrast mainland California and California Channel Island populations of five reptile species to understand the changes in their genomes, cells, and hormone physiology that alter their body size and reproduction on the islands. In this process, novel tools will be developed to study the genetic and hormone physiology of reptiles that can be used to understand the health of natural and zoo populations to aid conservation efforts and in agriculture. This project will engage over 30 undergraduate and graduate students (across three universities) and high school teachers in the research and will support the development of teaching modules based on scientific research. The findings from this research will improve our general understanding of how genes and environment determine complex traits, and more specifically will identify mechanisms regulating body size and reproduction in natural populations that are shared across animal species.Complex traits such as body size and reproduction are inherently regulated by molecular networks that are influenced by genetics and the environment, but the molecular mechanisms of how complex traits are regulated in and shared across natural populations are not well understood. Unraveling these molecular mechanisms will be a transformative step in our understanding of how complex traits are regulated in ecologically divergent populations. The Growth Hormone Insulin/Insulin-like Signaling (GH-IIS) network has been extensively studied in biomedical laboratory models and artificially selected species, for its role in growth, body size, and reproduction, thus making it an ideal candidate network for regulating these complex traits in natural systems. To understand the mechanistic basis for how complex traits can be altered in natural populations and at what level these mechanisms are shared across species, this project will contrast mainland and island populations for five reptile species, three that demonstrate insular dwarfism and two that do not. Data will be integrated across multiple levels of biological organization of the GH-IIS molecular network to pursue the following three aims: (1) quantify the relationship between GH-IIS hormone physiology and life-history traits in natural populations; (2) evaluate genetic divergence in the GH-IIS network; and (3) quantify divergence in cellular physiology and intracellular signaling. This project will further the understanding of which nodes within the network are responsive to ecological pressures in natural populations, and which are constrained. This new knowledge integrated across hierarchical levels of biology to identify mechanistic principals defining complex traits in natural populations.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.