Journal
SCIENCE ADVANCES
Volume 7, Issue 5, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abc3781
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Funding
- Marie Curie Intra European Fellowship within the Seventh European Community Framework Programme
- EPFL
- AgingX (SystemsX.ch)
- SNSF [IZRJZ3_164194]
- NIH [R01GM125859]
- Swiss National Science Foundation (SNF) [IZRJZ3_164194] Funding Source: Swiss National Science Foundation (SNF)
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Natural genetic variation plays a role in affecting circadian rhythms in fruit flies, leading to widespread tissue-specific circadian expression variation. Through analysis of a line with extreme deviation in circadian expression, a novel cry mutation was identified, providing further evidence for the importance of light-driven regulatory mechanisms.
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 (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.
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