Department of Physics, Universitá degli Studi di Milano and INFN, via Celoria 16, 20133 Milan, Italy.
Philos Trans A Math Phys Eng Sci. 2013 Aug 19;371(1999):20120469. doi: 10.1098/rsta.2012.0469. Print 2013 Sep 28.
The expression of genes in the cell is controlled by a complex interaction network involving proteins, RNA and DNA. The molecular events associated with the nodes of such a network take place on a variety of time scales, and thus cannot be regarded as instantaneous. In many cases, the cell is robust with respect to the delay in gene expression control, behaving as if it were instantaneous. However, there are specific cases in which delay gives rise to temporal oscillations. This is the case, for example, of the expression of tumour-suppressor protein p53, of protein Hes1, involved in the differentiation of stem cells, of NFkB and Wnt, in which case delay arises implicitly from the structure of the associated network. By means of delay rate equations, we study the kinetics of small regulatory networks, emphasizing the role of delay in an evolutionary context. These models suggest that oscillations are a typical outcome of the dynamics of regulatory networks, and evolution has to work to avoid them when not required (and not vice versa).
细胞中基因的表达受涉及蛋白质、RNA 和 DNA 的复杂相互作用网络控制。与这种网络节点相关的分子事件发生在各种时间尺度上，因此不能视为瞬时的。在许多情况下，细胞对基因表达控制的延迟具有鲁棒性，表现得好像是瞬时的。然而，在某些特定情况下，延迟会导致时间振荡。例如，肿瘤抑制蛋白 p53 的表达、参与干细胞分化的蛋白质 Hes1、NFkB 和 Wnt 的表达就是这种情况，在这种情况下，延迟是由相关网络的结构隐含产生的。我们通过延迟率方程研究小调节网络的动力学，强调延迟在进化背景下的作用。这些模型表明，振荡是调节网络动力学的典型结果，进化必须努力避免在不需要时出现振荡（反之则不然）。
