Gene Regulation: Single-Molecule Chemical Physics in a Natural Context

Summary

Single-molecule studies provide us with greater insights into the mechanistic details of chemical processes, but in natural biological systems, the deterministic formalism of ensemble kinetics has been considered to provide a sufficient phenomenology. The most striking exception to this view of the basis of systems biology is gene regulation. Most cells possess only one or two copies of any given gene. The proteins regulating these genes are also present in small numbers. Temporal averaging over DNA-protein binding events would return the problems of gene regulation to one of macroscopic kinetics, but this temporal averaging is not always adequate. The stability of genetic switches depends on the dynamics of individual gene binding events. A non-adiabatic formalism is required. In some models of gene switches, even more dramatically stochastic attractors apparently exist that have no deterministic counterparts. These attractors arise directly from the single-molecule nature of the gene and are analogous to extinction events in population biology.