Wittrup K D, Bailey J E
Department of Chemical Engineering, California Institute of Technology, Pasadena 91125.
J Theor Biol. 1988 Feb 21;130(4):481-92. doi: 10.1016/s0022-5193(88)80212-1.
A mathematical model of 2 mu plasmid recombinational amplification in Saccharomyces cerevisiae has been developed, based on mechanisms of 2 mu recombination and replication presented in the literature. A probabilistic description reveals the limits inherent in the recombinational mode of plasmid amplification. These limits correspond well with values calculated from reported results. In the model, copy number control is effected by the constitutive expression of a repressor of recombinase expression. Estimation of the model parameters is accomplished via a set of heuristic rules which restrict the feasible parameter space considerably. It is demonstrated that many parameter sets arbitrarily chosen from the feasible parameter space reproduce the observed characteristics of 2 mu plasmid amplification: rapid correction of downward copy number deviations, with a lack of strict control of steady-state copy number.
基于文献中提出的2μm质粒重组和复制机制,建立了酿酒酵母中2μm质粒重组扩增的数学模型。概率描述揭示了质粒扩增重组模式所固有的局限性。这些局限性与根据报道结果计算的值非常吻合。在该模型中,拷贝数控制通过重组酶表达阻遏物的组成型表达来实现。模型参数的估计是通过一组启发式规则完成的,这些规则大大限制了可行的参数空间。结果表明,从可行参数空间中任意选择的许多参数集都能重现观察到的2μm质粒扩增特征:拷贝数向下偏差的快速校正,而对稳态拷贝数缺乏严格控制。