hal-cyclicgene - A Classical Gene Regulatory Network Hal L....

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Unformatted text preview: A Classical Gene Regulatory Network Hal L. Smith * March 9, 2005 Tryptophan is one of the 20 amino acids that link together to form proteins. For humans it is an essential amino acid, we must get it from our diet since we cannot synthesize it. E. coli bacterial cells, however, can synthesize the amino acid tryptophan when it is not provided from the environment (e.g. the gut where it lives). It would be wasteful to synthesize tryptophan when it is readily available in the environment so E. coli have evolved a genetic switch (the trp operon) that turns off synthesis in this case and turns on synthesis when tryptophan is no longer present in the environment. The following model is based loosely on the control of tryptophan production by the trp operon. Although the trp gene codes for 5 enzymes that act on five substrates, or precursors, we simplify it a bit by considering only one of each. Our treatment follows Banks and Mahaffy [2], who considered a general negative feedback genetic control model. Their model, hence ours too, does not include transcriptional attenuation of the trp operon. See Santillan and Mackey [7] for a more realistic model of the trp operon. Our references contain further related material. Check the web page http://science.nhmccd.edu/biol/operon/ton.html for an animated description of the trp operon. 1 Reactions Name Symbol Description DNA DNA the gene of interest RNA Polymerase RNAP enzyme that reads DNA producing mRNA mRNA mRNA messenger RNA-working copy of the gene tRNA tRNA transfer RNA-converts mRNA code into protein E Enzyme E protein product of gene Precursor X substrate converted to tryptophan by catalyst E tryptophan T amino acid required by the cell Prerepressor P becomes a repressor when complexed with tryptophan Repressor R blocks the translation of DNA when bound to DNA Table 1: Main Players: the chemical species we will follow in the model Its useful to begin with a verbal model of the trp operon. It begins with RNA polymerase binding to DNA, the gene, and initiating the process of copying the DNA code to messenger RNA. This is called transcription. Messenger RNA then must be translated into protein, in our case, the enzyme E. This is facilitated by various transfer RNAs which bind a particular triplet of nucleotides and its corresponding amino acid and sequentially build the protein in the molecular machine called a ribosome. This process is called translation. The enzyme E then catalyzes a reaction whereby precursor molecule X is converted to tryptophan. The cell has now synthesized the needed protein. But now things get interesting. Two molecules of tryptophan can form a complex with a prerepressor molecule forming a repressor molecule, so-called because it can bind to a site on the DNA, preventing RNA polymerase from binding there, and thus shutting down transcription of the gene and the formation of tryptophan. In this way, tryptophan controls its own synthesis. If tryptophan is readily available in the cells environment then there will be enoughown synthesis....
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This note was uploaded on 09/12/2011 for the course MAP 4305 taught by Professor Deleenheer during the Summer '06 term at University of Florida.

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hal-cyclicgene - A Classical Gene Regulatory Network Hal L....

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