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Probability Controls The Molecule Of Life

24.05.2004


Thanks to biophysicists, statistics has reached the most intimate aspect of life – regulation of genes’ activity. Investigation on probabilistic aspects of molecular biology has been supported by the Russian Foundation for Basic Research and the INTAS Foundation.



Regulation of genes’ activity is one of the most important biological problems which has not been solved so far. A cell switches on and off its genes through multiple factors, which, if required, interact with certain sections of a chromosome or vice versa, leave them. While molecular biologists search for the mechanisms than ensure precise and uninterrupted control of genome’s activity, biophysics keep on saying that this is a statistical process, i.e., a probabilistic one, therefore, it cannot be absolutely precise. Specialists of the Engelgardt Institute of Molecular Biology (Russian Academy of Sciences) and the Faculty of Physics, Moscow State University, jointly with the colleagues from the Gumboldt University (Germany) have received equations that allow to assess statistically the regulatory factors/DNA interaction.

According to biophysicists’ opinion, molecules inside the cell move around as freely as in a drop of experimental solution: their concentrations go up and down slightly. Even an insignificant local change in molecule concentration capable of interaction with DNA may impact such interaction. Therefore, if two cells possessing an identical set of genes obviously differ from each other, they owe that to statistical deviations. It is impossible to measure the changes in concentration in experimental systems, therefore the researchers create mathematical models. In fact, these models are sometimes far from real ones (no infinite DNAs or DNAs all set by proteins exist in nature), but they help to evaluate the contribution of fortuity in the sanctum sanctorum of a cell - in regulation of genes’ work. The contribution is significant. Sometimes, due to statistical difference of concentration at the DNA section there may turn out to be eight to twelve regulatory molecules instead of ten. Sometimes, the value of hindrances reaches 17 percent.


One more reason for hindrances lies in competition. Speaking about regulation of work of some gene, researchers normally imply specific interaction of definite molecules with specific sections of DNA. However, on top of specific interaction, there also exists non-specific interaction. Multiple molecules are capable of combining with DNA, and they do so simply because they happened to be nearby. Accidental connection is not that strong, but on the other hand, a lot of “alien” molecules can set on DNA, the alien molecules hindering genes from specific interaction with regulatory proteins. All theoretically possible cases of competition for physical contact with DNA also yield to mathematical formulation.

From biophysicists point of view, DNA with proteins adsorbed on it may be viewed as a message, where relevant information is carried not only by the number of bound proteins, but also by the degree of its deviation from an average value. The researchers are convinced that it is impossible to investigate the control of genes’ activity without involvement of statistical thermodynamics of systems with a small number of particles. Although the objects of statistical thermodynamics exist not in bioplast, but in a test-tube filled with the solution of a complicated composition, the difference is normally disregarded by the authors of mathematical models.

Sergey Komarov | alfa
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