Pandey Rakesh, Armitage Judith P, Wadhams George H
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.
Present Address: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
BMC Syst Biol. 2017 Dec 28;11(1):146. doi: 10.1186/s12918-017-0489-y.
Photosynthetic (PS) gene expression in Rhodobacter sphaeroides is regulated in response to changes in light and redox conditions mainly by PrrB/A, FnrL and AppA/PpsR systems. The PrrB/A and FnrL systems activate the expression of them under anaerobic conditions while the AppA/PpsR system represses them under aerobic conditions. Recently, two mathematical models have been developed for the AppA/PpsR system and demonstrated how the interaction between AppA and PpsR could lead to a phenotype in which PS genes are repressed under semi-aerobic conditions. These models have also predicted that the transition from aerobic to anaerobic growth mode could occur via a bistable regime. However, they lack experimentally quantifiable inputs and outputs. Here, we extend one of them to include such quantities and combine all relevant micro-array data publically available for a PS gene of this bacterium and use that to parameterise the model. In addition, we hypothesise that the AppA/PpsR system alone might account for the observed trend of PS gene expression under semi-aerobic conditions.
Our extended model of the AppA/PpsR system includes the biological input of atmospheric oxygen concentration and an output of photosynthetic gene expression. Following our hypothesis that the AppA/PpsR system alone is sufficient to describe the overall trend of PS gene expression we parameterise the model and suggest that the rate of AppA reduction in vivo should be faster than its oxidation. Also, we show that despite both the reduced and oxidised forms of PpsR binding to the PS gene promoters in vitro, binding of the oxidised form as a repressor alone is sufficient to reproduce the observed PS gene expression pattern. Finally, the combination of model parameters which fit the biological data well are broadly consistent with those which were previously determined to be required for the system to show (i) the repression of PS genes under semi-aerobic conditions, and (ii) bistability.
We found that despite at least three pathways being involved in the regulation of photosynthetic genes, the AppA/PpsR system alone is capable of accounting for the observed trends in photosynthetic gene expression seen at different oxygen levels.
球形红杆菌中的光合（PS）基因表达主要通过PrrB/A、FnrL和AppA/PpsR系统响应光照和氧化还原条件的变化而受到调控。PrrB/A和FnrL系统在厌氧条件下激活它们的表达，而AppA/PpsR系统在需氧条件下抑制它们的表达。最近，针对AppA/PpsR系统开发了两个数学模型，并展示了AppA和PpsR之间的相互作用如何导致一种在半需氧条件下PS基因被抑制的表型。这些模型还预测，从需氧生长模式到厌氧生长模式的转变可能通过双稳态机制发生。然而，它们缺乏实验上可量化的输入和输出。在这里，我们扩展其中一个模型以纳入这些量，并结合该细菌一个PS基因所有公开可用的相关微阵列数据，并用其对模型进行参数化。此外，我们假设仅AppA/PpsR系统可能就可以解释在半需氧条件下观察到的PS基因表达趋势。
我们扩展的AppA/PpsR系统模型包括大气氧浓度的生物学输入和光合基因表达的输出。遵循我们的假设，即仅AppA/PpsR系统就足以描述PS基因表达的总体趋势，我们对模型进行参数化，并表明体内AppA的还原速率应快于其氧化速率。此外，我们表明，尽管PpsR的还原形式和氧化形式在体外均与PS基因启动子结合，但仅氧化形式作为阻遏物的结合就足以重现观察到的PS基因表达模式。最后，与生物学数据拟合良好的模型参数组合与先前确定系统显示（i）在半需氧条件下PS基因的抑制以及（ii）双稳态所需的参数大致一致。
我们发现，尽管至少有三条途径参与光合基因的调控，但仅AppA/PpsR系统就能解释在不同氧水平下观察到的光合基因表达趋势。
