Data_Sheet_2_Systematic Analysis of Mouse Genome Reveals Distinct Evolutionary and Functional Properties Among Circadian and Ultradian Genes.doc

In living organisms, biological clocks regulate 24 h (circadian) molecular, physiological, and behavioral rhythms to maintain homeostasis and synchrony with predictable environmental changes, in particular with those induced by Earth’s rotation on its axis. Harmonics of these circadian rhythms having periods of 8 and 12 h (ultradian) have been documented in several species. In mouse liver, harmonics of the 24-h period of gene transcription hallmarked genes oscillating with a frequency two or three times faster than circadian periodicity. Many of these harmonic transcripts enriched pathways regulating responses to environmental stress and coinciding preferentially with subjective dawn and dusk. At this time, the evolutionary history of genes with rhythmic expression is still poorly known and the role of length-of-day changes due to Earth’s rotation speed decrease over the last four billion years is totally ignored. We hypothesized that ultradian and stress anticipatory genes would be more evolutionarily conserved than circadian genes and background non-oscillating genes. To investigate this issue, we performed broad computational analyses of genes/proteins oscillating at different frequency ranges across several species and showed that ultradian genes/proteins, especially those oscillating with a 12-h periodicity, are more likely to be of ancient origin and essential in mice. In summary, our results show that genes with ultradian transcriptional patterns are more likely to be phylogenetically conserved and associated with the primeval and inevitable dawn/dusk transitions.

在活体内，生物钟（biological clock）可调控24小时周期的昼夜节律（circadian rhythm）性分子、生理及行为节律，以维持机体稳态，并与可预测的环境变化（尤其是地球自转轴自转引发的环境变化）保持同步。已有多项研究在多个物种中记录到这类昼夜节律的谐波，其周期为8小时与12小时，即超昼夜节律（ultradian rhythm）。在小鼠肝脏中，存在一类属于24小时基因转录节律谐波的基因，其振荡频率较昼夜节律快2至3倍。这些谐波转录本中，多数富集于调控环境应激响应的信号通路，且其表达峰值优先出现在主观黎明与主观黄昏时段。目前，节律表达基因的进化历程仍鲜为人知，而过去40亿年间地球自转速度减缓所引发的日长变化，其发挥的作用完全未被关注。本研究提出假设：超昼夜节律基因与应激预期基因，相较于昼夜节律基因及本底非振荡基因，具备更强的进化保守性。为验证这一假设，我们对多个物种中不同频率范围振荡的基因/蛋白质开展了大规模计算分析，结果显示：超昼夜节律基因/蛋白质（尤其是以12小时为周期振荡的基因/蛋白质）更可能起源古老，且在小鼠体内发挥必需功能。综上，本研究结果表明：具备超昼夜转录模式的基因，更易呈现系统发育保守性，且与原始且不可避免的黎明/黄昏环境转变密切相关。