Litovchenko, MariaMeireles-Filho, Antonio C. A.Frochaux, Michael, VBevers, Roel P. J.Prunotto, AlessioAnduaga, Ane MartinHollis, BrianGardeux, VincentBraman, Virginie S.Russeil, Julie M. C.Kadener, Sebastiandal Peraro, MatteoDeplancke, Bart2021-03-262021-03-262021-03-262021-01-0110.1126/sciadv.abc3781https://infoscience.epfl.ch/handle/20.500.14299/176549WOS:000614004600005Natural genetic variation affects circadian rhythms across the evolutionary tree, but the underlying molecular mechanisms are poorly understood. We investigated population-level, molecular circadian clock variation by generating >700 tissue-specific transcriptomes of Drosophila melanogaster (w(1118)) and 141 Drosophila Genetic Reference Panel (DGRP) lines. This comprehensive circadian gene expression atlas contains >1700 cycling genes including previously unknown central circadian clock components and tissue-specific regulators. Furthermore, >30% of DGRP lines exhibited aberrant circadian gene expression, revealing abundant genetic variation-mediated, intertissue circadian expression desynchrony. Genetic analysis of one line with the strongest deviating circadian expression uncovered a novel cry mutation that, as shown by protein structural modeling and brain immunohistochemistry, disrupts the light-driven flavin adenine dinucleotide cofactor photoreduction, providing in vivo support for the importance of this conserved photoentrainment mechanism. Together, our study revealed pervasive tissue-specific circadian expression variation with genetic variants acting upon tissue-specific regulatory networks to generate local gene expression oscillations.Multidisciplinary SciencesScience & Technology - Other Topicstext::journal::journal article::research article