Mutations in blind cavefish target the light regulated circadian clock gene period 2 Journal Article

Author(s): Ceinos Rosa Maria; Frigato Elena; Pagano Cristina; Frohlich Nadine; Negrini Pietro; Cavallari, Nicola; Vallone Daniela; Fuselli Silvia; Bertolucci Cristiano; Foulkes Nicholas S
Article Title: Mutations in blind cavefish target the light regulated circadian clock gene period 2
Affiliation IST Austria
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.
Journal Title: Scientific Reports
Volume: 8
Issue 1
ISSN: 20452322
Publisher: Nature Publishing Group  
Publication Place: England
Date Published: 2018-06-08
Start Page: 8754
Language: eng
DOI: 10.1038/s41598-018-27080-2
Notes: CB acknowledges research grants from the University of Ferrara (FAR2014-2017). Te research of DV and NSF was funded through the Helmholtz funding programme BIFTM. We also acknowledge support by the Deutsche Forschungsgemeinschaf and the open access publishing fund of the Karlsruhe Institute of Technology. CP was supported by the BMBF project MIE. RMC was supported under a contract by Xunta de Galicia (Spain) (programme I2C) cofunded by the European Social Fund (ESF) P.P.0000421S140.08 Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía and Centro Singular de Investigación Mariña-ECIMAT, Universidade de Vigo, Spain.
Open access: yes (OA journal)