Extensive tissue-specific expression variation and novel regulators underlying circadian behavior

Maria Litovchenko, Antonio C.A. Meireles-Filho, Michael V. Frochaux, Roel P.J. Bevers, Alessio Prunotto, Ane Martin Anduaga, Brian Hollis, Vincent Gardeux, Virginie S. Braman, Julie M.C. Russeil, Sebastian Kadener, Matteo dal Peraro, Bart Deplancke

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Article numbereabc3781
JournalScience Advances
Issue number5
StatePublished - Jan 29 2021

ASJC Scopus subject areas

  • General


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