The genetic basis of the circadian clock: identification of frq and FRQ as clock components in Neurospora.
The genetic basis of the circadian clock: identification of frq and FRQ as clock components in Neurospora.
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生物钟的遗传基础：将 frq 和 FRQ 鉴定为脉孢菌中的时钟成分。
DOI：
10.1002/9780470514597.ch2
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Garceau,NY
中科院分区：
文献类型：
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作者：
Dunlap,JC;Loros,JJ;Aronson,BD;Merrow,M;Crosthwaite,S;Bell-Pedersen,D;Johnson,K;Lindgren,K;Garceau,NY
用遗传学的方法来鉴定生物钟的组成部分已经在两个模型系统中取得了成功，即脉孢菌和果蝇。在每种生物体中，通过筛选影响生物钟的突变来识别基因，（frqinNeurospora，perinDrosophila）具有中枢时钟成分的特征：（1）每个基因的突变可以影响周期长度和温度补偿，这是昼夜节律系统的两个典型特征：（2）每个基因以昼夜节律的方式调节其自身转录的时间;以及（3）在rq的情况下，组成性升高的表达将使释放时钟的相位进入正常状态。然而，尽管有明显的遗传和分子相似性，这两个基因既不是分子同源物，也不是时间同源物。两个基因表达高峰的时间是不同的，frq表达在黎明后达到高峰，perexpression在午夜附近达到高峰。此外，尽管来自组成型启动子的perq的表达可以挽救缺乏该基因的果蝇中的节律性，但rq的组成型表达不会挽救脉孢菌frq缺失菌株中的节律性，并且事实上当在野生型菌株中表达时会导致节律性。这些数据表明，frq是和/或编码的昼夜节律振荡器的状态变量。最近的分子遗传学分析揭示了温度补偿的起源，并强烈表明这种特性是建立在振荡反馈回路中的，而不是附加在它上面的。似乎有道理的是，时钟是通过调整中心时钟组件（如frq）来调整和重置的，并且，通过扩展，per。
Genetic approaches to the identification of clock components have succeeded in two model systems,NeurosporaandDrosophila. In each organism, genes identified through screens for clock‐affecting mutations (frqinNeurospora, perinDrosophila) have subsequently been shown to have characteristics of central clock components: (1) mutations in each gene can affect period length and temperature compensation, two canonical characteristics of circadian systems; (2) each gene regulates the timing of its own transcription in a circadian manner; and (3) in the case offrq, constitutively elevated expression will set the phase of the clock on release into normal conditions. Despite clear genetic and molecular similarities, however, the two genes are neither molecular nor temporal homologues. The timing of peak expression is distinct in the two genes,frqexpression peaking after dawn andperexpression peaking near midnight. Also, although expression ofperfrom a constitutive promoter can rescue rhythmicity in a fly lacking the gene, constitutive expression offrqwill not rescue rhythmicity inNeurospora frq‐null strains, and in fact causes arrhythmicity when expressed in a wild‐type strain. These data suggest thatfrqis and/or encodes a state variable of the circadian oscillator. Recent molecular genetic analyses offrqhave shed light on the origin of temperature compensation and strongly suggest that this property is built into the oscillatory feedback loop rather than appended to it. It seems plausible that clocks are adjusted and reset through adjustments in central clock components such asfrq, and, by extension,per.