Kinetic Modeling of the Genetic Information Processes in a Minimal Cell

Kinetic Modeling of the Genetic Information Processes in a Minimal Cell
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DOI:
10.3389/fmolb.2019.00130
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发表时间:
2019-11-28
影响因子:
5
通讯作者:
Luthey-Schulten, Zaida
Luthey-Schulten, Zaida
中科院分区:
生物学3区
文献类型:
--
作者:
Thornburg, Zane R.;Melo, Marcelo C. R.;Luthey-Schulten, Zaida

文献摘要

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JCVI-syn3A是一种最小的细菌细胞,基因组为543 kbp,由493个基因组成。对于这种生长缓慢的最小细胞,我们最近建立了必需的代谢,包括从环境中运输所需的营养物质,基因图谱和全基因组蛋白质组学。在452个蛋白质编码基因中,143个与代谢有关,212个与遗传信息处理有关。利用全基因组蛋白质组学和从文献中实验测量的动力学参数,我们在这里建立了DNA复制、复制起始、转录和翻译的遗传信息过程的动力学模型,这些模型是随机求解的,平均超过1000个重复/细胞。该模型预测复制起始和DNA复制所需的平均时间分别为8分钟和50分钟,蛋白质和核糖体成分的数量在一个细胞周期内大约增加一倍。遗传信息处理模型与基本的代谢和细胞生长网络相结合,将为研究生命的基本原理提供一个强大的平台。
JCVI-syn3A is a minimal bacterial cell with a 543 kbp genome consisting of 493 genes. For this slow growing minimal cell with a 105 min doubling time, we recently established the essential metabolism including the transport of required nutrients from the environment, the gene map, and genome-wide proteomics. Of the 452 protein-coding genes, 143 are assigned to metabolism and 212 are assigned to genetic information processing. Using genome-wide proteomics and experimentally measured kinetic parameters from the literature we present here kinetic models for the genetic information processes of DNA replication, replication initiation, transcription, and translation which are solved stochastically and averaged over 1,000 replicates/cells. The model predicts the time required for replication initiation and DNA replication to be 8 and 50 min on average respectively and the number of proteins and ribosomal components to be approximately doubled in a cell cycle. The model of genetic information processing when combined with the essential metabolic and cell growth networks will provide a powerful platform for studying the fundamental principles of life.