RT Journal Article T1 Mutations in blind cavefish target the light-regulated circadian clock gene, period 2 A1 Ceinos Caride, Rosa María A1 Frigato, Elena A1 Pagano, Cristina A1 Fröhlich, Nadine A1 Negrini, Pietro A1 Cavallari, Nicola A1 Vallone, Daniela A1 Fuselli, Silvia A1 Bertolucci, Cristiano A1 Foulkes, Nicholas S K1 2401.13 Fisiología Animal K1 2411 Fisiología Humana K1 2409 Genética AB 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. PB Scientific Reports SN 20452322 YR 2018 FD 2018-06-08 LK http://hdl.handle.net/11093/4299 UL http://hdl.handle.net/11093/4299 LA eng NO Scientific Reports, 8(1): 8754 (2018) NO Universidad de Ferrara | Ref. FAR2014-2017 DS Investigo RD 08-feb-2025