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

Abstract:

: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.

journal_name

Sci Adv

journal_title

Science advances

authors

Litovchenko M,Meireles-Filho ACA,Frochaux MV,Bevers RPJ,Prunotto A,Anduaga AM,Hollis B,Gardeux V,Braman VS,Russeil JMC,Kadener S,Dal Peraro M,Deplancke B

doi

10.1126/sciadv.abc3781

subject

Has Abstract

pub_date

2021-01-29 00:00:00

issue

5

issn

2375-2548

pii

7/5/eabc3781

journal_volume

7

pub_type

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