Identification and study of adaptive mutations and phenotypes using laboratory growth of C. elegans

项目摘要/摘要 进化力量对人类发展疾病、社会行为、 和新陈代谢伴随着癌症的发展和对病原体的易感性。这些力量 在很大程度上决定了基因变化的类型以及影响这些特征或构成这些特征的基因。这个 麦格拉思实验室的目标是了解适应的遗传基础。基因的变化是什么？ 这可以增加健康，以及它们如何改变细胞活动和表型变化来实现 这?使用模式生物秀丽线虫的实验进化是解决 这些问题。线虫是一种遗传上易驯化、寿命短的线虫，可以用来研究 发育、行为和有性繁殖的进化。在接下来的五年里，麦格拉思实验室 将继续确定适应的遗传、细胞和表型基础，重点是 主要有三个方面。首先，信息素依赖的性状进化的遗传和细胞基础将是 特色化的。线虫释放并感觉到数十种粉虱苷信息素，这些信息素改变了一种 行为和发育特征的数量。这项工作将提供一个模型来理解如何 神经回路的进化是为了在新的环境中修改信息素信号。第二，功能界别 NURF染色质重塑复合体的进化将在一些线虫中表现出来 物种。染色质状态调节基因表达；它对决定细胞命运和 表型可塑性。染色质重构体的基因突变是许多疾病的重要风险因素 癌症。最后，将确定导致食物消费差异的基因和神经元。 肥胖是美国人常见的风险因素。线虫的基础工作可以帮助我们设计 减少人类肥胖的方法。总而言之，这项工作将提供一个关于适应的观点 多细胞生物体。

Project Summary/Abstract Evolutionary forces have important consequences for human diseases of development, social behavior, and metabolism along with the progression of cancers and susceptibility to pathogens. These forces largely determine the types of genetic changes and genes that influence or underlie these traits. The goal of the McGrath lab is to understand the genetic basis of adaptation. What are the genetic changes that can increase fitness and how do they modify cellular activity and phenotypic change to accomplish this? Experimental evolution using the model organism C. elegans is a powerful approach to address these questions. C. elegans, a genetically-tractable, short-lived nematode, can be used to study the evolution of development, behavior, and sexual reproduction. In the next five years, the McGrath lab will identify continue to identify the genetic, cellular, and phenotypic basis of adaptation, focusing on three main areas. First, the genetic and cellular basis of pheromone-dependent trait evolution will be characterized. C. elegans release and sense dozens of acaroside pheromones that modify a large number of behavioral and developmental traits. This work will provide a model for understanding how neural circuits evolve to modify pheromone signaling in new environments. Second, the functional evolution of the NURF chromatin remodeling complex will be characterized in a number of nematode species. Chromatin state regulates gene expression; it is important for determining cell fate and phenotypic plasticity. Genetic mutations in chromatin remodelers are an important risk factor for many cancers. Finally, genes and neurons responsible for differences in food consumption will be identified. Obesity is a common risk factor in Americans. Fundamental work in C. elegans could help us design approaches to decrease obesity in humans. In total, this work will provide a view of adaptation in a multicellular organism.