A blind circadian clock in cavefish reveals that opsins mediate peripheral clock photoreception.

A blind circadian clock in cavefish reveals that opsins mediate peripheral clock photoreception.
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DOI:
10.1371/journal.pbio.1001142
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发表时间:
2011-09
期刊:
影响因子:
9.8
通讯作者:
Foulkes NS
Foulkes NS
中科院分区:
生物学1区
文献类型:
--
作者:
Cavallari N;Frigato E;Vallone D;Fröhlich N;Lopez-Olmeda JF;Foà A;Berti R;Sánchez-Vázquez FJ;Bertolucci C;Foulkes NS

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在数百万年的永恒黑暗中进行的进化导致了非视觉视蛋白基因(黑素视蛋白和TMT视蛋白)的突变,并导致了洞穴鱼异常的、盲目的生物钟。生物钟主要通过光与昼夜周期同步。鱼类代表着令人着迷的模型,用于破译脊椎动物时钟的光输入路径,因为鱼的细胞时钟受直接光照射的调节。在这里,我们对生物钟进行了比较和功能分析,包括通常暴露在昼夜循环中的斑马鱼和在永久黑暗中进化的洞穴鱼物种。我们的结果表明,穴居鱼保留了一个食物携带的时钟,该时钟随亚食期振荡。然而,重要的是,这个时钟不是由光调节的。这项比较研究明确指出,视网膜外的两个光感受器黑素(Opn4m2)和TMT-opsin是外周时钟光输入途径的必要上游元件。生物钟是一种生理计时机制,使生物体能够预测和适应昼夜循环。由于它的运行周期不完全是24小时,因此必须每天根据光等信号进行重置,以确保它与昼夜周期保持同步。光调节生物钟的分子机制仍然不完全清楚。在这里,我们研究了一种在索马里永远黑暗的地下洞穴中进化了数百万年的洞穴鱼。像许多其他洞穴动物一样,这些鱼对它们的极端环境表现出惊人的适应能力,包括完全的眼睛退化。我们发现,尽管这种盲穴居鱼在持续不断的环境中进化,但它仍然保留着生物钟。然而,这种时钟的滴答周期非常长(近47小时),而且重要的是它不会对光做出反应。我们发现,失明并不是造成这种“失明”时钟的原因。具体地说,两种广泛表达的非视觉视蛋白感受器(黑素视蛋白和TMT视蛋白)的突变是导致洞鱼盲钟表型的原因。我们的工作说明了洞鱼在研究生物钟的进化和调节方面的巨大作用。
Evolution during millions of years in perpetual darkness leads to mutations in non-visual opsin genes (Melanopsin and TMT opsin) and an aberrant, blind circadian clock in cavefish. The circadian clock is synchronized with the day-night cycle primarily by light. Fish represent fascinating models for deciphering the light input pathway to the vertebrate clock since fish cell clocks are regulated by direct light exposure. Here we have performed a comparative, functional analysis of the circadian clock involving the zebrafish that is normally exposed to the day-night cycle and a cavefish species that has evolved in perpetual darkness. Our results reveal that the cavefish retains a food-entrainable clock that oscillates with an infradian period. Importantly, however, this clock is not regulated by light. This comparative study pinpoints the two extra-retinal photoreceptors Melanopsin (Opn4m2) and TMT-opsin as essential upstream elements of the peripheral clock light input pathway. The circadian clock is a physiological timing mechanism that allows organisms to anticipate and adapt to the day-night cycle. Since it ticks with a period that is not precisely 24 h, it is vital that it is reset on a daily basis by signals such as light to ensure that it remains synchronized with the day-night cycle. The molecular mechanisms whereby light regulates the clock remain incompletely understood. Here we have studied a cavefish that has evolved for millions of years in the perpetual darkness of subterranean caves in Somalia. Like many other cave animals, these fish display striking adaptations to their extreme environment, including complete eye degeneration. We show that despite evolving in a constant environment, this blind cavefish still retains a circadian clock. However, this clock ticks with an extremely long period (nearly 47 h), and importantly it does not respond to light. We reveal that eye loss does not account for this “blind” clock. Specifically, mutations of two widely expressed non-visual opsin photoreceptors (Melanopsin and TMT opsin) are responsible for the blind clock phenotype in the cavefish. Our work illustrates the great utility of cavefish for studying the evolution and regulation of the circadian clock.
DOI: 10.1371/journal.pbio.0050078
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期刊: PLoS biology
影响因子: 9.8
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