Department of Physics, Universidad de los Andes, Bogotá, Colombia.
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States of America.
Phys Biol. 2020 May 22;17(4):045002. doi: 10.1088/1478-3975/ab891c.
Classically, gene expression is modeled as a chemical process with reaction rates dependent on the concentration of the reactants (typically, DNA loci, plasmids, RNA, enzymes, etc). Other variables like cell size are in general ignored. Size dynamics can become an important variable due to the low number of many of these reactants, imperfectly symmetric cell partitioning and molecule segregation. In this work we measure the correlation between size and protein concentration by observing the gene expression of the RpOD gene from a low-copy plasmid in Escherichia coli during balanced growth in different media. A positive correlation was found, and we used it to examine possible models of cell size dynamics and plasmid replication. We implemented a previously developed model describing the full gene expression process including transcription, translation, loci replication, cell division and molecule segregation. By comparing with the observed correlation, we determine that the transcription rate must be proportional to the size times the number of plasmids. We discuss how fluctuations in plasmid segregation, due to the low copy number, can impose limits in this correlation.
传统上，基因表达被建模为一个化学反应过程，其反应速率取决于反应物的浓度（通常是 DNA 基因座、质粒、RNA、酶等）。其他变量，如细胞大小，通常被忽略。由于许多反应物数量较少、细胞分裂不完全对称和分子分离，大小动态可能成为一个重要的变量。在这项工作中，我们通过观察大肠杆菌中低拷贝质粒上 RpOD 基因的基因表达，在不同培养基中平衡生长时，测量大小和蛋白质浓度之间的相关性。发现存在正相关关系，我们用它来检验细胞大小动态和质粒复制的可能模型。我们实现了一个先前开发的模型，该模型描述了包括转录、翻译、基因座复制、细胞分裂和分子分离在内的完整基因表达过程。通过与观察到的相关性进行比较，我们确定转录率必须与质粒数量的大小成正比。我们讨论了由于拷贝数较低，质粒分离的波动如何对这种相关性施加限制。
