All multicellular organisms embed endogenous circadian oscillators or clocks that rhythmically regulate a wide variety of processes in response to daily environmental cycles. Previous molecular studies using rhythmic mutants for several model systems have identified a set of genes responsible for rhythmic activities and illustrated the molecular mechanisms underlying how disruptions in circadian rhythms are associated with the sort of aberrant cell cycling. However, the wide use of these forward genetic studies is impaired by a limited number of mutations that can be identified or induced only in a single genome, limiting the identification of many other conserved or non-conserved clock genes. Genetic linkage or association mapping provides an unprecedented glimpse into the genome-wide scanning and characterization of genes underlying circadian rhythms. The implementation of sophisticated statistical models into genetic mapping studies can not only identify key clock genes or clock quantitative trait loci (cQTL) but also, more importantly, reveal a complete atlas of the genetic control mechanisms constituted by gene interactomes. Here, we introduce and review an advanced statistical mechanics framework for coalescing all possible clock genes into intricate but well-organized interaction networks that regulate rhythmic cycles. The application of this framework to widely available mapping populations will reshape and further our understanding of the genetic signatures behind circadian rhythms for an enlarged range of species including microbes, plants, and humans.

中文翻译：

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基于昼夜节律的时钟基因网络的统计力学

所有多细胞生物都嵌入了内源性昼夜节律振荡器或时钟，它们有节奏地调节各种过程以响应日常环境周期。先前对几个模型系统使用节律突变体的分子研究已经确定了一组负责节律活动的基因，并说明了昼夜节律中断如何与异常细胞周期相关联的分子机制。然而，这些正向遗传研究的广泛应用受到了数量有限的突变的影响，这些突变只能在单个基因组中识别或诱导，限制了许多其他保守或非保守时钟基因的识别。遗传连锁或关联作图提供了对昼夜节律基础基因的全基因组扫描和表征的前所未有的一瞥。将复杂的统计模型应用于遗传作图研究，不仅可以识别关键时钟基因或时钟数量性状基因座 (cQTL)，更重要的是，可以揭示基因相互作用组构成的遗传控制机制的完整图谱。在这里，我们介绍并回顾了一个先进的统计力学框架，用于将所有可能的时钟基因合并成复杂但组织良好的交互网络，以调节节律周期。