Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks.
Bottom Line: The gene regulatory network (GRN) is the central decision-making module of the cell.BQS explains many of the small- and large-scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response.BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation.
Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom email@example.com.Show MeSH
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Mentions: Qualitative Stability is compromised to a very small degree in the GRN of E. coli by the two small, but ‘illegal’ feedback loops shown in Figure 6A,B and highlighted in Figure 6—figure supplement 1. Three aspects are noteworthy. Firstly, of the seven 2-node feedback loops in the E. coli GRN, four are embedded into the two potentially unstable motifs depicted in Figure 6A,B, whilst the other three are isolated from other feedback loops and so are either stable or likely to act as switches. Secondly, the genes comprising the two illegal motifs are involved in drug resistance (Ariza et al., 1995; Martin and Rosner, 2002; Nishino et al., 2008; Keseler et al., 2011; Figure 6C) and/or acid resistance (Sayed et al., 2007; Keseler et al., 2011; Figure 6C). This raises the possibility that limited instances of deviation from BQS may arise through evolution as a short-term expediency allowing survival in a changing environment. Thirdly, both loops share a remarkably similar sub-structure: two linked 2-gene feedback loops connected by one link into a 3-node feedback loop. It has been previously shown in chemical networks that such a configuration can display chaotic behaviour (Sensse and Eiswirth, 2005). It is tempting to speculate that these illegal motifs act as localized sources of chaos, allowing a cell population to quickly explore very diverse gene expression levels, thus accelerating the emergence of resistant phenotypes (Lopez-Maury et al., 2008). Moreover, compatible with the idea that chaotic behaviour should be tightly controlled, most of the genes depicted in Figure 6A,B are highly regulated (Figure 6D).10.7554/eLife.02863.025Figure 6.The two ‘illegal’ feedback loops in E. coli.
Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom firstname.lastname@example.org.