Abstract

Author SummaryThe 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.

Highlights

  • The circadian clock is a highly conserved, physiological timing mechanism that allows organisms to anticipate and adapt to daily environmental changes and it is synchronized primarily by light

  • We have studied a cavefish that has evolved for millions of years in the perpetual darkness of subterranean caves in Somalia

  • We show that despite evolving in a constant environment, this blind cavefish still retains a circadian clock

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Summary

Introduction

The circadian clock is a highly conserved, physiological timing mechanism that allows organisms to anticipate and adapt to daily environmental changes and it is synchronized primarily by light. In non-mammalian vertebrates, photoreceptors located outside of the retina (in the pineal complex and in the deep brain) have been implicated in the regulation of the circadian timing system [2]. At the core of the vertebrate circadian clock is a transcription translation feedback loop mechanism composed of activator and repressor clock proteins [3]. The zebrafish (Danio rerio) represents a fascinating model to study the mechanisms whereby light regulates the clock. Fundamental questions concerning the identity of the widely expressed photoreceptor molecules and how they signal to peripheral clocks remain unanswered. A set of widely expressed opsins, one cryptochrome homolog, and flavin-containing oxidases have all been implicated as candidate peripheral photoreceptors [7,8,9]

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