Depending on how you look at it, large gene-expression networks are dauntingly complicated or, if you're a mathematical modeller, elegantly simple and reducible to a discrete number of meaningful ON/OFF switches. A modelling study has begun to link these network 'building blocks' together by showing that an optimal output is obtained when two such switches are combined.
There are several well-characterized classes of switch-like elements, but this study concentrated on positive-feedback loops, in which A activates B and B activates A. Feedback loops operate in many signalling pathways, with some processes — such as oocyte maturation in frogs and the polarization of yeast cells — relying on more complicated switch arrangements, such as the coupling of two positive-feedback loops. This arrangement is initially rather puzzling: why combine two switches when a single one will carry out exactly the same function?
A computational modelling approach revealed a reason for the extra layer of complexity: slow loops are stable switches, but cannot transit between states quickly; by contrast, fast loops make for unstable (noisy) switches, but are quick at switching between states. Coupling two switches of the same kind together brings no overall benefit over having a single switch, but combining a fast and a slow switch yields an optimal output — that of a fast yet robust, reliable switch.
This type of dual positive-feedback loop is the one that is seen in the sub-circuits of many biological systems, and we now understand why this might be. This work also highlights the comforting thought that the details of a circuit are in fact dispensable, provided we have a good handle on the wiring.
References
ORIGINAL RESEARCH PAPER
Brandman, O. et al. Interlinked fast and slow positive feedback loops drive reliable cell divisions. Science 310, 496–498 (2005)
FURTHER READING
Bornholdt, S. Less is more in modelling large genetic networks. Science 310, 449–451 (2005)
Wall, M. E. et al. Design of gene circuits: lessons from bacteria. Nature Rev. Genet. 5, 34–42 (2004)
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Casci, T. Linked-up loops: a reliable means of control. Nat Rev Genet 6, 878 (2005). https://doi.org/10.1038/nrg1761
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DOI: https://doi.org/10.1038/nrg1761
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