果蝇昼夜节律调控网络的一个修正模型

A REVISED MODE OF DROSOPHILA CIRCADIAN REGULATION NETWORK

PER和TIM是果蝇两个重要的生物钟蛋白.以往的研究一直认为PER和TIM是在细胞质中结合为二聚体并以二聚体的形式进入细胞核.但2006年Pablo Meyer等人的实验研究表明,PER/TIM复合物在细胞质中分离,然后PER和TIM在很短的时间内独立进入细胞核.根据该项实验结果,我们对果蝇昼夜节律调控模型进行了修正,修正模型反映了per和tim基因的转录翻译及蛋白质的翻译后修饰过程,二次磷酸化的蛋白质PER(P2)、TIM(T2)分别独立进入细胞核并参与后续的调控过程.计算了修正模型的振荡周期并由此确定了新模型所引入的参数值.对修正模型的振荡节律进行数值分析,发现修正模型振荡节律在DD、LD条件下均产生了近于24h的持续周期振荡而在LL条件下呈现出振荡衰减,这些结果与原模型相似,反映出所建模型的合理性.但修正模型对参数对称性的依赖性则更加强烈,具体解释还有待于进一步的工作.

PER and TIM are two important clock proteins in Drosophila. In the previous research, PER and TIM were considered to combine as heterodimers in the cytoplasm, then the heterodimers PER/TIM can be transported into the nucleus. But the experimental research, made by Pablo Meyer et al. in 2006, has indicated that PER/ TIM heterodimers dissociated in cytoplasm, and then PER and TIM can be independently transferred into the nu- cleus in a narrow time frame. This paper revised the circadian regulation model of Drosophila according to the a- bove experimental result. The revised model considers the process of the transcription and translation of gene per and tim, the protein post-translational modification, the separate entry of the secondary phosphorylation of protein PER （P2） and TIM （T2） into the nucleus and the subsequent regulatory process. Then we calculate the periodic oscillation of the revised model, and determine the values of new parameters introduced by the modification process. Subsequently we calculate the oscillation rhythm of the revised model. It is found that the revised model exhibits similar properties as original model. That is to say, the oscillation is periodic and the rhythm is close to 24h under the condition of DD and LD, but the oscillation is damping under the condition of LL. The results re- flect the rationality of the revised model. On the other hand the revised model shows more dependencies on the parameter symmetry than the original model. The detailed explanation for this phenomenon needs further work.