Spatial Fluctuations and the Flipping of the Genetic Switch in a Cellular System
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Spatial uctuations and the ipping of the genetic switch in a cellular system Ralf Metzler Department of Physics, Massachusetts Institute of Technology 77 Massachusetts Ave., Cambridge, MA 02139 Electronic address: [email protected] Abstract { It has been realised that noise plays an important r^ole in cellular processes where uctuation induced number uctuations of certain messenger molecules become non{negligible, due to the small total number of these molecules within one cell. In the following, it is argued that spatial
uctuations of such molecules and their impact on genetic switches should be considered as well.
Bacteriophage T4, the so-called phage, and its parasitosis with the bacterium Escherichia coli has been studied as a paradigm for genetic switches for over half a century. The corkscrew shaped phage, see Fig. 1, injects its DNA into E.coli where it fuses with the host DNA. From this moment on, the phage's genetic information is copied each time E.coli reproduces itself through cell division, if the parasite-host system is dormant (lysogeny). If not, uses its host as a miniature chemical plant to reproduce itself, until so many copies of are produced that the host cell virtually bursts, and thus a swarm of new phages is released (lysis). The decision between either route within this if-then loop depends on whether certain antagonist messenger molecules, repressor R or cro, bind to the active operator site on the DNA and thus allow for the transcription of the corresponding genes. The interplay between messenger molecules and the subsequent decision which one of two genes is transcribed, i.e., which blueprint is copied and applied, is called the genetic switch [1]. The basic mode of operation of a genetic switch is shown in Fig. 2. 1 T8.6.1
Figure 1: Left: Bacteriophage T4, the phage. The head contains the DNA which is injected into the host cell E.coli through the corkscrew-like pipe. Right: Like a cannoli coated with demerara sugar|the E.coli cell under attack. Each tiny spot represents a phage. One can, in essence, distinguish between co-operative and non{co-operative switches. In a non{co-operative switch, a bound R molecule dissociates with some rate constant |nc diss. If it is not replaced by another R, but a cro molecule binds to the adjacent operator instead, the process of lysis occurs. In the co-operative scenario, in contrast, on average two repressor units bind to the gene; one R binds much stronger and facilitates the binding of the other R. Now, one R dissociates, but as long as the other R is still present, only new R can bind to its vacant operator site. Cro binding, and therefore lysis, can only occur, if both R dissociate, due to the co-operative bond formation a much less likely event. This is how nature created extremely robust control mechanisms for sensitive issues such as reproduction [1]. The chemical processes of transcription, production and degradation of the messenger molecules are a priori noisy. As the total number of these 2 T8.6.2
R O1 O2 cro O1 O2
R I R II O
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