Harbison Susan T, Kumar Shailesh, Huang Wen, McCoy Lenovia J, Smith Kirklin R, Mackay Trudy F C
Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
Laboratory of Systems Genetics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Behav Genet. 2019 Jan;49(1):60-82. doi: 10.1007/s10519-018-9932-0. Epub 2018 Oct 19.
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.
昼夜节律影响从睡眠-清醒周期到体温等生理过程，并由高度保守的循环分子控制。尽管昼夜节律钟的机制基础已为人所知数十年，但昼夜节律在自然界中的变化程度以及这种变化的潜在遗传基础仍未得到很好的理解。我们在果蝇遗传参考面板（DGRP）中测量了昼夜节律周期（Ʈ）和节律性指数，并观察到两者都存在广泛的遗传变异。七个DGRP品系具有性二态性无节律性，一个品系具有异常长的Ʈ。全基因组分析在268个基因中鉴定出584个多态性。我们观察到预测在长周期品系和对照中相互作用的九个基因的转录本之间存在差异，以及与经典生物钟基因之间的差异。针对这些基因的突变/RNA干扰敲低也影响昼夜节律行为。我们的观察结果表明，复杂的遗传相互作用影响昼夜节律表型的高水平变异。
