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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A rapid genome-scale response of the transcriptional oscillator to perturbation reveals a period-doubling path to phenotypic change
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A rapid genome-scale response of the transcriptional oscillator to perturbation reveals a period-doubling path to phenotypic change

机译：转录振荡器对扰动的快速基因组规模反应揭示了表型变化的倍增途径

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摘要

Perturbation of the gated-synchrony system in yeast with phenelzine, an antidepressant drug used in the treatment of affective disorders in humans, leads to a rapid lengthening in the period of the genome-wide transcriptional oscillation. The effect is a concerted, genome-scale change in expression that is first seen in genes maximally expressed in the late-reductive phase of the cycle, doubling the length of the reductive phase within two cycles after treatment. Clustering of genes based on their temporal patterns of expression yielded just three super clusters whose trajectories through time could then be mapped into a simple 3D figure. In contrast to transcripts in the late-reductive phase, most transcripts do not show transients in expression relative to others in their temporal cluster but change their period in a concerted fashion. Mapping the trajectories of the transcripts into low-dimensional surfaces that can be represented by simple systems of differential equations provides a readily testable model of the dynamic architecture of phenotype. In this system, period doubling may be a preferred pathway for phenotypic change. As a practical matter, low-amplitude, genome-wide oscillations, a ubiquitous but often unrecognized attribute of phenotype, could be a source of seemingly intractable biological noise in microarray studies.
机译：苯菲尔嗪是一种用于治疗人类情感障碍的抗抑郁药，可干扰酵母中的门控共生系统，从而导致全基因组转录振荡周期的迅速延长。这种作用是一致的，基因组规模的表达变化，该变化首先在周期的晚期还原阶段最大表达的基因中出现，在治疗后两个周期内还原阶段的长度加倍。根据基因的时间表达模式进行的基因聚类仅产生了三个超级簇，它们的时间轨迹可以映射到一个简单的3D图形中。与还原后期的转录本相比，大多数转录本在其时间簇中相对于其他转录本而言并未表现出瞬时表达，而是以一致的方式改变了它们的时期。将成绩单的轨迹映射到可以用微分方程的简单系统表示的低维表面，可以为表型的动态结构提供易于测试的模型。在这个系统中，周期加倍可能是表型改变的优选途径。实际上，低振幅，全基因组振荡是表型普遍存在但通常无法识别的属性，可能是微阵列研究中看似棘手的生物噪声的来源。

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