Abstract
Circadian rhythms influence physiological processes from sleep–wake cycles to body temperature and are controlled by highly conserved cycling molecules. Although the mechanistic basis of the circadian clock has been known for decades, the extent to which circadian rhythms vary in nature and the underlying genetic basis for that variation is not well understood. We measured circadian period (Ʈ) and rhythmicity index in the Drosophila Genetic Reference Panel (DGRP) and observed extensive genetic variation in both. Seven DGRP lines had sexually dimorphic arrhythmicity and one line had an exceptionally long Ʈ. Genome-wide analyses identified 584 polymorphisms in 268 genes. We observed differences among transcripts for nine genes predicted to interact among themselves and canonical clock genes in the long period line and a control. Mutations/RNAi knockdown targeting these genes also affected circadian behavior. Our observations reveal that complex genetic interactions influence high levels of variation in circadian phenotypes.
Highlights
Circadian rhythms are endogenous cycles present in almost all living organisms
Heritability was relatively low for Maximum Entropy Spectral Analysis (MESA) period (H2 = 0.17), consistent with previous estimates of heritability in wild-derived populations (Emery et al 1995), but higher for χ2 period (H2 = 0.39)
The distributions of MESA and χ2 period across the Drosophila Genetic Reference Panel (DGRP) were quite different from one another (Fig. 1e–h)
Summary
Circadian rhythms are endogenous cycles present in almost all living organisms. They affect myriads of biological processes in humans, such as sleep/wake cycles, body temperature, hormone levels, heart rate, and even cognitive performance (Van Dongen et al 2004). Circadian rhythms may play a fundamental role in human health (Zee et al 2014). Disruption to circadian rhythms has been associated with detrimental neurobehavioral consequences. Circadian disruptions often precede the development of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, though whether they have a causal role in these conditions is unknown (Mattis and Sehgal 2016; Videnovic and Zee 2015). Circadian misalignment, often manifested as rotating or shifting work schedules, has been associated with increased hypertension, Type 2 diabetes, total cholesterol, and cardiovascular
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