Litovchenko, M., Meireles-Filho, A.C.A., Frochaux, M.V., Bevers, R.P.J., Prunotto, A., Anduaga, A.M., Hollis, B., Gardeux, V., Braman, V.S., Russeil, J.M.C., Kadener, S., Dal Peraro, M., Deplancke, B. (2021). Extensive tissue-specific expression variation and novel regulators underlying circadian behavior.  Sci. Adv. 7(5): eabc3781.

FBrf0247917

Research paper

Natural 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 (w1118) 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.

PMC7846174 (PMC) (EuropePMC)