Department of Integrative Biology, The University of Texas at Austin, Austin, TX, United States of America.
PLoS One. 2024 Oct 31;19(10):e0313039. doi: 10.1371/journal.pone.0313039. eCollection 2024.
Bacteriophage ϕX174 has been widely used as a model organism to study fundamental processes in molecular biology. However, several aspects of ϕX174 gene regulation are not fully resolved. Here we construct a computational model for ϕX174 and use the model to study gene regulation during the phage infection cycle. We estimate the relative strengths of transcription regulatory elements (promoters and terminators) by fitting the model to transcriptomics data. We show that the specific arrangement of a promoter followed immediately by a terminator, which occurs naturally in the ϕX174 genome, poses a parameter identifiability problem for the model, since the activity of one element can be partially compensated for by the other. We also simulate ϕX174 gene expression with two additional, putative transcription regulatory elements that have been proposed in prior studies. We find that the activities of these putative elements are estimated to be weak, and that variation in ϕX174 transcript abundances can be adequately explained without them. Overall, our work demonstrates that ϕX174 gene regulation is well described by the canonical set of promoters and terminators widely used in the literature.
噬菌 X174 已被广泛用作研究分子生物学基本过程的模式生物。然而,噬菌 X174 的基因调控的几个方面尚未完全解决。在这里,我们构建了一个噬菌 X174 的计算模型,并使用该模型研究了噬菌体感染周期中的基因调控。我们通过将模型拟合到转录组学数据来估计转录调控元件(启动子和终止子)的相对强度。我们表明,在噬菌 X174 基因组中自然发生的启动子紧接着终止子的特定排列对模型的参数可识别性构成了问题,因为一个元件的活性可以部分被另一个元件补偿。我们还使用先前研究中提出的另外两个假定的转录调控元件模拟了噬菌 X174 的基因表达。我们发现这些假定元件的活性估计较弱,并且没有它们也可以充分解释噬菌 X174 转录物丰度的变化。总的来说,我们的工作表明,噬菌 X174 的基因调控可以通过文献中广泛使用的标准启动子和终止子集很好地描述。