Team:LCG-UNAM-Mexico/Notebook/2008-September

Lac promoter synthesis rate

van Hoek F, Hogeweg P (2007) The effect of stochasticity on the Lac Operon: An evolutionary perspective. PLoS Comput Biol 3 (6): E111

The article's objective, as you can infer from the title, is to evaluate the effect of stochasticity in the evolution of a Promoter. In order to do so they built a comprehensive model including every parameter involved in Transcription and translation. They measure some parameters but they depend mostly on literature to define them.

They both do a deterministic and a Stochastic analysis. To generate a Stochastic model they added one parameter, the average burst size of protein translation (protein translation occurs in bursts, after a several mRNA is synthesized proteins can be translated from the same mRNA). This was possible because when an mRNA molecule is translated it can not be degraded. Therefore after each translation it can either be translated again (p) or be degraded (1-p). This suggests that protein production occurs in bursts with a burst size geometrically distributed. After they compared their noise levels in the model with the experimental noise measurements they found good agreement.

Transcription they used to model a two-dimensional Hill-function dependent on the cAMP concentration and alloctase. (repressa the glucose and lactose Operon via cAMP activates the Operon via allolactose).

They use 11 biochemical parameters, including three of special importance for us:

a, when the rate Transcription RNA Polymerase is bound to the DNA, but CRP and Laci are not. evolva: initial value: 1.1 × 10-7 mM / min

b, The Transcription rate when both RNA Polymerase and CRP are bound, but Laci is not bound to the DNA. evolva: initial value: 2.2 × 10-5 mM / min

c,''leakiness,''the Transcription rate when RNA Polymerase is not bound to the DNA. evolva: initial value 5.5 × 10-10 mM / min

They modele binomially protein degradation, assuming that cell when to divide proteins are divided randomly between the cells. However in a population of non-Dividing cells this "dilution" can not be taken in account.

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