MATHEMATICAL MODELING OF THE EXPERIMENTAL EVOLUTION OF TRANSGENIC BACTERIA: “PLASMID PARADOX”

A. Brilkov, E. Brilkova, I. Jabrun, V. Ganusov, Yu. Loginov, A. Shuvaev
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Abstract

In the present work, a mathematical model for the distribution of transgenic bacteria cells by the number of plasmids contained in them is constructed. This makes it possible to study the patterns of survival of transgenic microorganisms under certain environmental conditions, taking into account various characteristics of transgenic strains, for example, the stability of plasmids in new cells, the “population cost” of maintaining conjugative and non-conjugative plasmids, the efficiency of expression of genes cloned on plasmids, and others. The "plasmid paradox" lies in the fact that although the presence of plasmids containing cloned genes usually reduces the specific growth rate of transgenic bacteria, but with prolonged growth of bacteria under non-selective conditions ("experimental evolution", 20-30 or more generations of the original form without antibiotics) “cost of fitness” is reduced by an order of magnitude or two. An analysis of the experimental results leads to the conclusion that this is due to a change in the difference in the growth rates of plasmid and plasmid-free cells, with a change in the probability of formation of plasmid-free cells, the copy number of plasmids, and the expression of cloned genes in cells of transgenic bacteria under various environmental conditions.
转基因细菌实验进化的数学模型:"质粒悖论"
在本研究中,我们根据转基因细菌细胞中所含质粒的数量,构建了一个转基因细菌细胞分布的数学模型。这样就可以研究转基因微生物在特定环境条件下的生存模式,同时考虑到转基因菌株的各种特性,例如质粒在新细胞中的稳定性、维持共轭和非共轭质粒的 "种群成本"、质粒上克隆基因的表达效率等。质粒悖论 "在于,虽然含有克隆基因的质粒的存在通常会降低转基因细菌的特定生长率,但随着细菌在非选择性条件下的长期生长("实验性进化",在不使用抗生素的情况下以原始形式生长 20-30 代或更多代),"适应性成本 "会降低一两个数量级。对实验结果进行分析后得出的结论是,这是由于质粒细胞和无质粒细胞的生长率差异发生了变化,无质粒细胞形成的概率、质粒的拷贝数以及在各种环境条件下转基因细菌细胞中克隆基因的表达发生了变化。
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