Experimental Evolution of Anticipation

描述（由申请人提供）： 这个提议的目的是探索生物如何进化以预测其环境的周期性变化的进化机制。生物钟已经进化到可以预测一天24小时的光/暗周期，并作为研究生物体如何适应环境振荡的理想模型。生物钟将许多生物体的生理机能与一天中最有益的时间相协调，而哺乳动物的这一过程的中断与抑郁症、失眠症、冠心病发作和癌症有关。尽管时钟在协调功能与时间方面发挥着广泛的作用，但对进化时钟的机制或益处还没有很好的理解。利用出芽酵母酿酒酵母（Saccharomycescerevisiae），本研究试图分析生物钟的进化，其目的如下：（1）通过操纵内源性信号通路来设计和改进振荡电路，（2）将随机开关进化为规则振荡器，（3）通过随机突变和选择重新进化生物钟。这些目标将利用传统的遗传和分子生物学方法来设计和表征所有目标的信号通路。使用荧光激活细胞分选（FACS）选择进化表型的实验进化方法将用于目标2和3。这些目标旨在研究产生时钟的振荡电路的狭义生物化学细节，以及生物体进化出内部时钟的广泛变化。酵母将被使用，因为它们缺乏可检测的内源性时钟，这允许一个从头进化，并且酵母中的遗传变化比高等真核生物更容易跟踪。更一般地说，这一建议旨在解决一般的进化原则，新的生化功能是如何通过自然选择产生的。有一个显着缺乏实验证据，详细说明生物与环境之间的关系的生化性质，和照明的一般机制将提供有益的洞察健康问题，如耐药细菌，癌症的进展，和流行病爆发的开始。人体已经适应了通过生物钟来感知环境的周期性变化，但对这种感知机制的整体生物学贡献还没有很好地理解。数据表明，生物钟的破坏与各种疾病有关，如抑郁症，心脏病和癌症。该建议旨在探索和确定生物体如何发展感知环境周期性变化的能力，以及其对维持健康的整体贡献。

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.