具有热鲁棒性的适应性基因调控网络
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摘要
通过对三节点基因调控网络的枚举、参数空间的随机采样以及动力学模拟,找到具有热鲁棒性(即温度补偿)的适应性基因转录调控网络,对其进行结构分析表明,存在3种最基本的结构可以实现具有热鲁棒性的适应性动力学功能,复杂的适应性网络都以此3种网络为核心骨架。为了考察三节点适应性网络的适应性对网络动力学中各参数改变的敏感度,计算了各参数相应的控制系数。对控制系数的聚类分析表明,三节点功能网络实现热鲁棒的机制为温度隔离,即尽管网络中所有的速率参数都依赖于温度,但仅输出节点的生成和降解速率明显偏离0且具有相反的符号,大多数热鲁棒适应性都通过输出节点的拮抗平衡调节来实现。
Through the enumeration of the three-node gene regulatory network, the random sampling of the parameter space and the dynamics simulation, the adaptive gene transcriptional regulation networks with thermal robustness(namely temperature compensation) are found. The structural analysis of the thermally robust adaptive networks shows that there are three basic structures that can achieve adaptive dynamics with thermal robustness,and the complex adaptive networks with thermal robustness uses these three networks as the core skeletons. In order to investigate the sensitivity of the adaptability of the three-node adaptive network to the changes of various parameters in the network dynamics, the authors calculate the corresponding control coefficients of each parameter.The clustering analysis of the control coefficients shows that the mechanism of the three-node functional network to achieve thermal robustness is temperature isolation, that is, although all rate parameters in the network are temperature dependent, only the generation and degradation rates of the output nodes deviate significantly from zero and have opposite signs. Most thermal robustness is achieved by the antagonistic balance adjustment of the output nodes.
Through the enumeration of the three-node gene regulatory network, the random sampling of the parameter space and the dynamics simulation, the adaptive gene transcriptional regulation networks with thermal robustness(namely temperature compensation) are found. The structural analysis of the thermally robust adaptive networks shows that there are three basic structures that can achieve adaptive dynamics with thermal robustness,and the complex adaptive networks with thermal robustness uses these three networks as the core skeletons. In order to investigate the sensitivity of the adaptability of the three-node adaptive network to the changes of various parameters in the network dynamics, the authors calculate the corresponding control coefficients of each parameter.The clustering analysis of the control coefficients shows that the mechanism of the three-node functional network to achieve thermal robustness is temperature isolation, that is, although all rate parameters in the network are temperature dependent, only the generation and degradation rates of the output nodes deviate significantly from zero and have opposite signs. Most thermal robustness is achieved by the antagonistic balance adjustment of the output nodes.
引文
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[11]Oleksiuk O,Jakovljevic V,Vladimirov N,et al.Thermal Robustness of Signaling in Bacterial Chemotaxis.Cell,2011,145(2):312-321
[12]Shimizu H,Woodcock S A,Wilkin M B,et al.Compensatory flux changes within an endocytic trafficking network maintain thermal robustness of Notch signaling.Cell,2014,157(5):1160-1174
[13]Ma W,Trusina A,El-Samad H,et al.Defining network topologies that can achieve biochemical adaptation.Cell,2009,138(4):760-773
[14]Yan L,Ouyang Q,Wang H.Dose-response aligned circuits in signaling systems.PLoS One,2012,7(4):34727-34736
[15]Wagner A.Circuit topology and the evolution of robustness in two-gene circadian oscillators.Proceedings of the National Academy of Sciences,2005,102(33):11775-11780
[16]Lim W A,Lee C M,Tang C.Design principles of regulatory networks:searching for the molecular algorithms of the cell.Molecular Cell,2013,49(2):202-212
[17]Ma W,Lai L,Ouyang Q,et al.Robustness and modular design of the Drosophila segment polarity network.Molecular Systems Biology,2006,2(1):Article 70
[18]Mejia Y X,Mao H,Forde N R,et al.Thermal probing of E.coli RNA polymerase off-pathway mechanisms.J Mol Biol,2008,382(3):628-637
[19]Ruoff P,Christensen M K,Wolf J,et al.Temperature dependency and temperature compensation in a model of yeast glycolytic oscillations.Biophysical Chemistry,2003,106(2):179-192
[20]Iman R L.Latin hypercube sampling.Chichester:American Cancer Society,2014
[2]Tseng Y Y,Hunt S M,Heintzen C,et al.Comprehensive modelling of the Neurospora circadian clock and its temperature compensation.PLoS Comput Biol,2012,8(3):1002437-1002449
[3]Hazel J R,Prosser C L.Molecular mechanisms of temperature compensation in poikilotherms.Physiological Reviews,1974,54(3):620-677
[4]Zakhartsev M V,De Wachter B,Sartoris F J,et al.Thermal physiology of the common eelpout(Zoarces viviparus).Journal of Comparative Physiology B,2003,173(5):365-378
[5]Ruoff P,Zakhartsev M,Westerhoff H V.Temperature compensation through systems biology.FEBS J,2007,274(4):940-950
[6]Wu L,Ouyang Q,Wang H.Robust network topologies for generating oscillations with temperature-independent periods.PLoS One,2017,12(2):63-81
[7]Shi W,Ma W,Xiong L,et al.Adaptation with transcriptional regulation.Scientific Reports,2017,7(1):339-349
[8]Cao L H,Jing B Y,Yang D,et al.Distinct signaling of Drosophila chemoreceptors in olfactory sensory neurons.Proceedings of the National Academy of Sciences,2016,113(7):902-911
[9]El-Samad H,Goff J P,Khammash M.Calcium homeostasis and parturient hypocalcemia:an integral feedback perspective.Journal of Theoretical Biology,2002,214(1):17-29
[10]Gomez-Marin A,Duistermars B J,Frye M A,et al.Mechanisms of odor-tracking:multiple sensors for enhanced perception and behavior.Front Cell Neurosci,2010,4:Article 6
[11]Oleksiuk O,Jakovljevic V,Vladimirov N,et al.Thermal Robustness of Signaling in Bacterial Chemotaxis.Cell,2011,145(2):312-321
[12]Shimizu H,Woodcock S A,Wilkin M B,et al.Compensatory flux changes within an endocytic trafficking network maintain thermal robustness of Notch signaling.Cell,2014,157(5):1160-1174
[13]Ma W,Trusina A,El-Samad H,et al.Defining network topologies that can achieve biochemical adaptation.Cell,2009,138(4):760-773
[14]Yan L,Ouyang Q,Wang H.Dose-response aligned circuits in signaling systems.PLoS One,2012,7(4):34727-34736
[15]Wagner A.Circuit topology and the evolution of robustness in two-gene circadian oscillators.Proceedings of the National Academy of Sciences,2005,102(33):11775-11780
[16]Lim W A,Lee C M,Tang C.Design principles of regulatory networks:searching for the molecular algorithms of the cell.Molecular Cell,2013,49(2):202-212
[17]Ma W,Lai L,Ouyang Q,et al.Robustness and modular design of the Drosophila segment polarity network.Molecular Systems Biology,2006,2(1):Article 70
[18]Mejia Y X,Mao H,Forde N R,et al.Thermal probing of E.coli RNA polymerase off-pathway mechanisms.J Mol Biol,2008,382(3):628-637
[19]Ruoff P,Christensen M K,Wolf J,et al.Temperature dependency and temperature compensation in a model of yeast glycolytic oscillations.Biophysical Chemistry,2003,106(2):179-192
[20]Iman R L.Latin hypercube sampling.Chichester:American Cancer Society,2014