Experimental Evolution of Anticipation

描述(由申请人提供)： 这项提议的目的是探索生物体如何进化以预测其环境的周期性变化的进化机制。生物钟已经进化到预测24小时一天中的光/暗周期，并成为研究生物体如何适应其环境中的振荡的理想模型。生物钟在一天中最有益的时间协调许多生物体的生理，而哺乳动物这一过程的中断与抑郁、失眠、冠状动脉心脏病发作和癌症有关。尽管时钟在协调功能与时间方面发挥着广泛的作用，但进化时钟的机制或好处还没有被很好地理解。利用萌芽酵母酿酒酵母，本方案旨在分析生物钟的进化，其目的如下：(1)通过操纵内源信号通路来设计和改进振荡电路；(2)将随机开关进化成规则振荡器；(3)通过随机突变和选择来从头进化出生物钟。这些AIMS将利用传统的遗传和分子生物学方法来设计和表征所有AIMS的信号通路。目标2和目标3将使用一种使用荧光激活细胞分类(FACS)来选择进化表型的实验进化方法。该目标旨在研究产生时钟的振荡电路的狭窄生化细节，以及生物体的广泛变化使其进化出内部时钟。酵母将被使用，因为它们缺乏可检测到的内源性时钟，允许一种从头开始的进化，而且酵母中的基因变化比高等真核生物中的更容易跟踪。更广泛地说，这项提议试图解决自然选择如何产生新的生化功能的一般进化原则。目前还缺乏详细说明有机体和环境之间关系的生化性质的实验证据，阐明一般机制将为了解抗生素耐药性细菌、癌症进展和流行病爆发等健康问题提供有益的见解。人体通过生物钟已经适应了环境的周期性变化，但生物对这种感知机制的整体贡献还不是很清楚。数据表明，生物钟的紊乱与各种疾病有关，如抑郁症、心脏病和癌症。这项建议是为了探索和确定生物体如何发展感知其环境周期性变化的能力，以及它对维持健康的总体贡献。

DESCRIPTION (provided by applicant): The objective of this proposal is to explore the evolutionary mechanisms to how organisms evolve to anticipate periodic changes in their environment. The circadian clock has evolved to anticipate the light/dark cycles of the 24-hour day, and serves as a ideal model for investigating how organisms have adapted to oscillations in their environment. Clocks coordinate the physiology of many organisms with the most beneficial time of day, and disruption of this process in mammals has been linked to depression, insomnia, coronary heart attacks, and cancer. Despite the broad role of clocks in coordinating function with time, the mechanism or benefit to evolving clocks is not well understood. Using the budding yeast, Saccharomyces cerevisiae, this proposal seeks to analyze the evolution of clocks with the following aims: (1) Engineer and improved an oscillating circuit by manipulating an endogenous signaling pathway, (2) Evolved a stochastic switch into a regular oscillator, and (3) Evolve a circadian clock de novo by random mutation and selection. These aims will utilize both conventional genetic and molecular biology approaches to engineer and characterize signaling pathways for all aims. An experimental evolution approach using fluorescence activated cell sorting (FACS) to select for evolved phenotypes will be used for aims 2 and 3. The aims are designed to investigate both the narrow biochemical detail of oscillating circuits that give rise to clocks, and the broad changes to an organism has it evolves an internal clock. Yeast will be used because they lack a detectable endogenous clock, which permits the evolution of one de novo, and genetic changes are much easier to track in yeast than in higher eukaryotes. More generally, this proposal seeks to address the general evolutionary principles to how new biochemical functions arise by natural selection. There is a significant lack of experimental evidence detailing the biochemical nature of the relationship between orgnanism and environment, and illuminating general mechanisms will provide beneficial insight to health issues such as antibiotic-resistent bacteria, cancer progression, and the onset of epidemic outbreaks. The human body has adapted to sense cyclical changes in the environment by virtue of a circadian clock, but the overall biological contribution to this sensing mechanisms is not well understood. Data suggests that disruption of the clock is linked to various diseases such as depression, heart disease, and cancer. This proposal is outlined to explore and determine how organisms develop the ability to sense periodic changes in their environment, and its overall contribution to maintaining health.