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Mutations in blind cavefish target the light-regulated circadian clock gene, period 2.


ABSTRACT: Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors.

SUBMITTER: Ceinos RM 

PROVIDER: S-EPMC5993827 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Mutations in blind cavefish target the light-regulated circadian clock gene, period 2.

Ceinos Rosa Maria RM   Frigato Elena E   Pagano Cristina C   Fröhlich Nadine N   Negrini Pietro P   Cavallari Nicola N   Vallone Daniela D   Fuselli Silvia S   Bertolucci Cristiano C   Foulkes Nicholas S NS  

Scientific reports 20180608 1


Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind cloc  ...[more]

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