Phylogeny of Sleep

描述（由申请人提供）：大约7000万美国人患有睡眠问题；其中，近60%的人患有慢性睡眠障碍。睡眠障碍在美国每年的医疗保健账单中约占160亿美元，但有关睡眠功能和进化的基本问题仍未得到解答，也未得到充分研究。本研究的目的是研究哺乳动物两种主要睡眠状态REM（快速眼动或活跃睡眠）和NREM（非快速眼动或安静睡眠）的不同进化历史和生理功能，使用最先进的分析程序来评估系统发育变化。这样的调查将阐明每种睡眠状态在睡眠恢复能力中的作用，并将阐明每种睡眠状态的单独功能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系统发育的比较分析来研究REM和NREM是如何进化的，以及与其他特征的关系。过去二十年的研究在了解特定物种的睡眠方面取得了重大进展。同时，分子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检查这些树的宏观进化变化的工具。因此，比较方法进入了一个新的“黄金时代”——但是这些方法还没有被应用到有关独特睡眠状态功能演变的问题上。我们的具体目标是：1)开发一个可在网上访问的哺乳动物睡眠模式比较数据库。详尽的文献检索表明，目前大约有150个物种的睡眠配额质量数据。我们在这篇重新提交的论文中提出的分析表明，过去几十年在实验室中获得的睡眠配额数据通常是可靠和有效的睡眠过程指标，因为它们发生在野外。收集这些数据的研究人员在记录睡眠值以近似研究中动物的自然状态时付出了艰苦的努力。我们的其他目标包括分析在目标1下构建的数据集。这些目标包括2)研究异速生长趋势，量化系统发育信号和识别混杂变量。4)建立睡眠状态的成本-收益模型：建立睡眠的成本-收益模型将使我们能够进一步探索快速眼动/非快速眼动的独立功能，并得出在人类主要睡眠障碍中通常发生的两种睡眠状态的睡眠持续时间扰动的临床意义。

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.