Yin Daiqing, Yu Zhenpeng, Jiang Haojia, Chong Yujie, Zhong Cuijuan, Xu Shixia, Yang Guang
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, Guangdong 511458, China.
Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Mol Biol Evol. 2024 Dec 6;41(12). doi: 10.1093/molbev/msae257.
Marine mammals have evolved unihemispheric slow-wave sleep, a unique state during which one cerebral hemisphere sleeps while the other remains awake, to mitigate the fundamental conflict between sleep and wakefulness. However, the underlying mechanisms remain largely unclear. Here, we use a comparative phylogenetic approach to analyze genes associated with light-dependent circadian mechanisms, aiming to reconstruct the evolution of the circadian rhythm pathway in mammals and to identify adaptively changed components likely to have contributed to the development of unihemispheric slow-wave sleep. Specifically, among eight genes with shared signals of positive selection in two unihemispheric slow-wave sleep-specific lineages, seven genes showed direct evidence of affecting sleep and spontaneous movements. Both in vitro and in vivo experiments indicated that functional innovation in cetacean and non-phocid pinniped FBXL21, which was found to undergo positive selection, may be beneficial for decoupling sleep-wake patterns from daily rhythms to sustain continuous swimming. For cetaceans exhibiting only unihemispheric slow-wave sleep, we identified 73 genes as rapidly evolving and 92 genes containing unique amino acid substitutions. Functional assays showed that a cetacean-specific mutation (F411Y) in NFIL3 led to a decrease in repressor activity and protein stability. Furthermore, convergent amino acid replacements detected in genes related to Ca2+ signaling and CREB phosphorylation suggest their crucial role in unihemispheric slow-wave sleep adaptation. Overall, this study enhances our understanding of the evolutionary mechanisms underlying unihemispheric slow-wave sleep and provides a foundation for investigating how circadian rhythm changes contribute to variations in sleep and circadian behavior.
海洋哺乳动物进化出了单侧脑慢波睡眠，这是一种独特的状态，在此期间，一个脑半球睡眠，而另一个脑半球保持清醒，以缓解睡眠和清醒之间的根本冲突。然而，其潜在机制在很大程度上仍不清楚。在这里，我们使用比较系统发育方法来分析与光依赖的昼夜节律机制相关的基因，旨在重建哺乳动物昼夜节律途径的进化，并识别可能有助于单侧脑慢波睡眠发展的适应性变化成分。具体而言，在两个单侧脑慢波睡眠特异性谱系中具有共同正选择信号的八个基因中，有七个基因显示出影响睡眠和自发运动的直接证据。体外和体内实验均表明，在经历正选择的鲸类和非海狗科鳍足类动物的FBXL21中的功能创新，可能有利于使睡眠-觉醒模式与日常节律脱钩，以维持持续游泳。对于仅表现出单侧脑慢波睡眠的鲸类动物，我们鉴定出73个快速进化的基因和92个含有独特氨基酸替换的基因。功能分析表明，NFIL3中的一个鲸类特异性突变（F411Y）导致阻遏物活性和蛋白质稳定性降低。此外，在与Ca2+信号传导和CREB磷酸化相关的基因中检测到的趋同氨基酸替换表明它们在单侧脑慢波睡眠适应中起关键作用。总体而言，这项研究增进了我们对单侧脑慢波睡眠潜在进化机制的理解，并为研究昼夜节律变化如何导致睡眠和昼夜行为变化提供了基础。
