PNAS:这个基因突变后,你每天只需睡5小时!
2018/03/25
充足的睡眠对身体和精神健康都是必不可少的。大多数人每晚需要约8-8.5小时的睡眠才能感觉良好。不过,科学家们发现,一种基因突变,能够使人每天只需睡5小时左右。那么,这背后的机制又是怎样的呢?
2009年,加州大学旧金山分校的神经学教授Ying-Hui Fu博士在“自然短睡者家庭(a family of natural short sleeper)”中发现了基因DEC2的一种突变。该突变使得短睡者在正常时间(晚上11点到12点之间)上床睡觉,但在第二天早晨5点就会自然醒来。

Fu教授说:“这些人并没有训练自己早起。他们生来如此。”


图片来源:PNAS(DOI:https://doi.org/10.1073/pnas.1801693115)

3月12日,最新发表在PNAS上题为“DEC2 modulates orexin expression and regulates sleep”的研究中,Fu教授的实验室借助小鼠模型,揭示了DEC2基因的错义突变是如何让短睡者靠仅仅几小时的睡眠就能存活下来,并茁壮成长的。

研究使用的基因工程小鼠具有在人类短睡者中被观察到的相同DEC2基因突变。分析结果显示,DEC2能够帮助控制食欲肽(orexin,一种与维持清醒有关的激素)水平。 短睡者中DEC2的突变似乎是通过部分释放orexin生产的刹车而起作用。


图片来源:16sucai

具体来说,该研究发现,正常情况下,在晚上,DEC2可能是通过抑制开启orexin产生的基因——MyoD1”来降低人的警觉水平;而黎明前,DEC2会“逐渐消失(fades away)”,允许MyoD1刺激orexin的表达,唤醒你,并让你全天保持清醒。

“DEC2的作用可能是确保orexin在一天中合适的时间表达合适的数量,从而让orexin的水平与昼夜节律相匹配。” Fu教授解释道。

然而,在短睡者中,突变的发生削弱了DEC2抑制MyoD1的能力,这使得他们会产生更多的orexin,从而保持清醒地时间更长。

总结来说,作者们认为,DEC2 是orexin表达的转录抑制因子,而突变DEC2的抑制活性变得更弱了,这导致orexin表达增加。他们还表示,这项研究是理解DEC2调节睡眠背后分子机制的第一步。

参考资料:

Scientists discover how gene mutation reduces the need for sleep

DEC2 modulates orexin expression and regulates sleep

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  • DEC2 modulates orexin expression and regulates sleep

    Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene (BHLHE41) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin, also known as hypocretin (Hcrt), gene expression is increased in the mouse model expressing the mutant hDEC2 transgene (hDEC2-P384R). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal. In cell culture, DEC2 suppressed prepro-orexin promoter-luc (ore-luc) expression through cis-acting E-box elements. The mutant DEC2 has less repressor activity than WT-DEC2, resulting in increased orexin expression. DEC2-binding affinity for the prepro-orexin gene promoter is decreased by the P384R mutation, likely due to weakened interaction with other transcription factors. In vivo, the decreased immobility time of the mutant transgenic mice is attenuated by an orexin receptor antagonist. Our results suggested that DEC2 regulates sleep/wake duration, at least in part, by modulating the neuropeptide hormone orexin.

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