基因转录模型系列的分析延迟分布。

IF 2.6 4区 工程技术 Q1 Mathematics Mathematical Biosciences and Engineering Pub Date : 2024-06-13 DOI:10.3934/mbe.2024273
S Hossein Hosseini, Marc R Roussel
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引用次数: 0

摘要

旨在描述基因网络时间演化的模型必须以某种方式包括转录(以 DNA 为模板合成 RNA)和翻译(以 RNA 为模板合成蛋白质)。在真核生物中,用于转录的 DNA 模板可能很长,通常由数以万计的核苷酸组成,转录过程中可能会出现长时间的停顿。因此,转录可以持续许多分钟,有时甚至长达数小时。在基因表达模型中引入延迟以考虑转录和翻译时间的做法由来已久。在这里,我们研究了一系列详细的转录模型,其中包括起始、延伸和终止反应。我们建立了一个计算转录时间分布的框架,并在一些典型情况下计算出了这些分布。对于伸长反应,固定延迟是一个很好的模型,条件是伸长反应与起始和终止反应相比速度很快,而且没有出现长时间停顿的位点。然后,模型中的起始和终止阶段会产生一个非对称的延迟分布,而伸长会使这一分布发生移动,移动量与伸长延迟相应。当启动和终止相对较快时,伸长时间的分布可以用高斯分布来近似。将该高斯与起始和终止时间分布卷积,可得到转录时间分布的另一个解析近似值。如果在伸长过程中存在长时间的停顿,由于所考虑的模型系列具有模块性,伸长阶段可以划分为产生简单延迟的反应(通过没有长时间停顿区域的伸长)和必须明确考虑等待时间分布的反应(起始、终止和通过可能出现长时间停顿区域的运动)。在这些情况下,转录时间的分布再次涉及一个非简单的部分,以及由于快速伸长过程而产生的偏移。
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Analytic delay distributions for a family of gene transcription models.

Models intended to describe the time evolution of a gene network must somehow include transcription, the DNA-templated synthesis of RNA, and translation, the RNA-templated synthesis of proteins. In eukaryotes, the DNA template for transcription can be very long, often consisting of tens of thousands of nucleotides, and lengthy pauses may punctuate this process. Accordingly, transcription can last for many minutes, in some cases hours. There is a long history of introducing delays in gene expression models to take the transcription and translation times into account. Here we study a family of detailed transcription models that includes initiation, elongation, and termination reactions. We establish a framework for computing the distribution of transcription times, and work out these distributions for some typical cases. For elongation, a fixed delay is a good model provided elongation is fast compared to initiation and termination, and there are no sites where long pauses occur. The initiation and termination phases of the model then generate a nontrivial delay distribution, and elongation shifts this distribution by an amount corresponding to the elongation delay. When initiation and termination are relatively fast, the distribution of elongation times can be approximated by a Gaussian. A convolution of this Gaussian with the initiation and termination time distributions gives another analytic approximation to the transcription time distribution. If there are long pauses during elongation, because of the modularity of the family of models considered, the elongation phase can be partitioned into reactions generating a simple delay (elongation through regions where there are no long pauses), and reactions whose distribution of waiting times must be considered explicitly (initiation, termination, and motion through regions where long pauses are likely). In these cases, the distribution of transcription times again involves a nontrivial part and a shift due to fast elongation processes.

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来源期刊
Mathematical Biosciences and Engineering
Mathematical Biosciences and Engineering 工程技术-数学跨学科应用
CiteScore
3.90
自引率
7.70%
发文量
586
审稿时长
>12 weeks
期刊介绍: Mathematical Biosciences and Engineering (MBE) is an interdisciplinary Open Access journal promoting cutting-edge research, technology transfer and knowledge translation about complex data and information processing. MBE publishes Research articles (long and original research); Communications (short and novel research); Expository papers; Technology Transfer and Knowledge Translation reports (description of new technologies and products); Announcements and Industrial Progress and News (announcements and even advertisement, including major conferences).
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