The dynamics of genetic control in the cell: the good and bad of being late

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).