Characteristics of transcriptional activity in nonlinear dynamics of genetic regulatory networks.

Simon Rosenfeld
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引用次数: 9

Abstract

Microarray measurements of mRNA abundances is a standard tool for evaluation of transcriptional activity in functional genomics. The methodology underlying these measurements assumes existence of a direct link between transcription levels, that is, gene-specific mRNA copy numbers present in the cell, and transcription rates, that is, the numbers of gene-specific mRNA molecules synthesized per unit of time. In this paper, the question of whether or not such a tight interdependence may exist is examined in the context of nonlinear dynamics of genetic regulatory networks. Using the equations of chemical kinetics, a model has been constructed that is capable of explicitly taking into consideration nonlinear interactions between the genes through the teamwork of transcription factors. Jacobian analysis of stability has shown that steady state equilibrium is impossible in such systems. However, phase space compressibility is found to be negative, thus suggesting that asymptotic stability may exist and assume either the form of limit cycle or of a chaotic attractor. It is argued that in rapidly fluctuating or chaotic systems, direct evaluation of transcription rates through transcription levels is highly problematic. It is also noted that even if a hypothetical steady state did exist, the knowledge of transcription levels alone would not be sufficient for the evaluation of transcription rates; an additional set of parameters, namely the mRNA decay rates, would be required. An overall conclusion of the work is that the measurements of mRNA abundances are not truly representative of the functionality of genes and structural fidelity of the genetic codes.

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遗传调控网络非线性动力学中的转录活性特征。
微阵列测量mRNA丰度是功能基因组学中评估转录活性的标准工具。这些测量的基础方法假设在转录水平(即细胞中存在的基因特异性mRNA拷贝数)和转录率(即单位时间内合成的基因特异性mRNA分子数)之间存在直接联系。在本文中,是否存在这种紧密的相互依存关系的问题是在遗传调控网络的非线性动力学背景下进行检查。利用化学动力学方程,构建了一个模型,该模型能够通过转录因子的团队合作明确考虑基因之间的非线性相互作用。稳定性的雅可比分析表明,在这种系统中稳态平衡是不可能的。然而,发现相空间压缩率为负,从而表明可能存在渐近稳定性,并以极限环或混沌吸引子的形式存在。有人认为,在快速波动或混沌系统中,通过转录水平直接评估转录率是非常有问题的。还需要指出的是,即使假设的稳定状态确实存在,单靠转录水平的知识也不足以评估转录率;还需要一组额外的参数,即mRNA的衰减率。这项工作的总体结论是,mRNA丰度的测量并不能真正代表基因的功能和遗传密码的结构保真度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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