Phylogeny of Sleep

描述（申请人提供）：大约有7000万美国人患有睡眠问题;其中近60%患有慢性睡眠障碍。睡眠障碍约占美国年度医疗保健法案的160亿美元，但有关睡眠功能和进化的基本问题仍然没有答案和研究不足。本提案的目的是调查不同的进化历史和两个主要的哺乳动物睡眠状态REM（快速眼动或主动睡眠）和NREM（非REM或安静睡眠）的生理功能，使用最先进的分析程序评估系统发育的变化。这样的研究将澄清每种睡眠状态在睡眠恢复能力中的作用，并阐明每种睡眠状态的单独功能的崩溃可能导致临床睡眠障碍的方式。我们的方法是使用基于遗传学的比较分析来研究快速眼动和非快速眼动是如何进化的，以及与哪些其他特征相关。过去二十年的研究在理解特定物种的睡眠方面取得了重大进展。与此同时，分子生物学的进步使得生成系统发育树成为可能，而新的分析方法提供了在这些树上检查宏观进化变化的工具。因此，比较方法学已经进入了一个新的“黄金时代”，但这些方法还没有被应用到有关独特的睡眠状态功能的演变问题。我们的具体目标是：1）开发一个网络访问的哺乳动物睡眠模式的比较数据库。详尽的文献检索表明，关于睡眠配额的质量数据现在可用于大约150个物种。我们在这份重新提交的报告中提出了分析，表明过去几十年在实验室中获得的睡眠配额数据通常是睡眠过程的可靠和有效指标，因为它们发生在野外。收集这些数据的研究者在记录睡眠值时付出了艰苦的努力，以接近研究动物的自然条件。我们的其他目标包括分析目标1下构建的数据集。这些目标包括2）调查异速生长趋势，量化系统发育信号和识别混杂变量。3)测试活跃/REM与安静非REM睡眠的演变和功能的先验假设：4）开发睡眠状态的成本效益模型：开发睡眠的成本效益模型将允许我们进一步探索REM/NREM的独立功能，并推导出两种睡眠状态的睡眠持续时间扰动的临床意义，这通常发生在主要的人类睡眠障碍中。

DESCRIPTION (provided by applicant): About 70 million Americans suffer from a sleep problem; among them, nearly 60 percent have a chronic sleep disorder. Sleep disorders account for approximately $16 Billion of the annual US health care bill, yet basic questions about the functions and evolution of sleep remain unanswered and understudied. The purpose of this proposal is to investigate the distinct evolutionary histories and physiological functions of the two major mammalian sleep states REM (rapid eye movement or active sleep) and NREM (non-REM or quiet sleep) using state of the art analytic procedures for assessment of phylogenetic change. Such an investigation would clarify the role of each of the sleep states in the restorative capacities of sleep and would illuminate the ways in which breakdowns in the separate functions of each sleep state could lead to clinical disorders of sleep. Our approach is to use phylogeny-based comparative analysis to examine how, and in association with which other traits, REM and NREM evolved. Research during the past two decades has produced major advances in understanding sleep within particular species. Simultaneously, molecular advances have made it possible to generate phylogenetic trees, while new analytical methods provide the tools to examine macroevolutionary change on these trees. Thus, comparative methodology has entered a new "Golden Age" - but these methods have yet to be applied to questions concerning the evolution of distinctive sleep state functions. Our specific aims are to 1) Develop a Web-accessible comparative database on mammalian sleep patterns. Exhaustive literature searches have shown that quality data on sleep quotas is now available for approximately 150 species. We present analyses in this re-submittal that show that data on sleep quotas that were obtained over the past few decades in the laboratory are generally reliable and valid indices of sleep processes as they occur in the wild. Investigators who collected these data made strenuous efforts when recording sleep values to approximate natural conditions for the animals under study. Our other aims involve analyses of the data set constructed under Aim 1. These aims include 2) Investigate allometric trends, quantify phylogenetic signal and identify confounding variables. 3) Test a priori hypotheses for the evolution of and functions of active/REM versus quiet non-REM Sleep: 4) Develop a cost-benefit model of sleep states: Development of a cost-benefit model of sleep will allow us to further explore independent functions of REM/NREM and to derive clinical implications of perturbations in sleep durations of the two sleep states that typically occur in major human sleep disorders.