Experimental Evolution of Circadian Oscillators

描述（由申请人提供）：昼夜节律是人类健康的重要组成部分。不适当的日常调节/睡眠阶段和其他生物钟控制参数与几种类型的抑郁症、肥胖/代谢综合征和心血管疾病有关。在细胞水平上，昼夜节律起搏器调节细胞分裂、代谢和基因表达网络。导致昼夜节律特殊特征（特别是其精确的24小时时间常数和温度补偿）进化的选择压力尚未确定。具有短时间常数的内在反馈的代谢过程如何通过选择压力来建立一个自我维持的24小时振荡器，并进行温度补偿？这个问题的答案对我们理解细胞周期、基因转录网络、“系统”生物学、进化过程和时间生物学具有广泛的意义。该项目将对具有昼夜节律特征的生物节律进行实验进化，以确定相关的选择压力，以及特定的代谢途径是否倾向于自我维持的生物振荡器的进化。具有遗传能力的单细胞生物将受到各种环境循环（光/暗、UV- B、温度）的影响，以确定哪些条件可以导致具有昼夜节律特征的生物振荡器的进化。这些振荡子的成功进化将通过细胞周期和代谢事件的发光报告来评估。

DESCRIPTION (provided by applicant): Circadian (daily) rhythms are a crucial component of human health. Inappropriate daily regulation/phasing of sleep and other clock-controlled parameters is associated with several types of depression, obesity/metabolic syndrome, and cardiovascular disease. At the cellular level, circadian pacemakers regulate cell division, metabolism, and gene expression networks. The selective pressures that led to the evolution of the special characteristics of circadian rhythms (esp. their precise 24 h time constant and temperature compensation) have not been identified. How can metabolic processes that intrinsically feed back with short time constants be recruited by selective pressures to the establishment of a self-sustained 24 h oscillator that is temperature compensated? The answer to this question has broad significance to our understanding of cell cycles, gene transcriptional networks, "Systems" biology, evolutionary processes, and chronobiology. This project will undertake an experimental evolution of biological rhythms that have circadian characteristics in a quest to identify relevant selective pressures and whether particular metabolic pathways are predisposed towards the evolution of self-sustained biological oscillators. Single cell organisms with genetic capabilities will be subjected to a variety of environmental cycles (light/dark, UV- B, temperature) to ascertain which conditions can lead to the evolution of biological oscillators with circadian characteristics. The successful evolution of such oscillators will be assessed with luminescence reporters of cell cycle and metabolic events.