A DISCRETE DYNAMICAL SYSTEM ARISING IN MOLECULAR BIOLOGY

SELEX (Systematic Evolution of Ligands by EXponential Enrichment) is an iterative separation process by which a pool of nucleic acids that bind with varying specificities to a fixed target molecule or a fixed mixture of target molecules, i.e., single or multiple targets, can be separated into one or more pools of pure nucleic acids. In its simplest form, as introduced in [6], the initial pool is combined with the target and the products separated from the mixture of bound and unbound nucleic acids. The nucleic acids bound to the products are then separated from the target. The resulting pool of nucleic acids is expanded using PCR (polymerase chain reaction) to bring the pool size back up to the concentration of the initial pool and the process is then repeated. At each stage the pool is richer in nucleic acids that bind best to the target. In case that the target has multiple components, one obtains a mixture of nucleic acids that bind best to at least one of the components. A further refinement of multiple target SELEX, known as alternate SELEX, is described below. This process permits one to specify which nucleic acids bind best to each component of the target. These processes give rise to discrete dynamical systems based on consideration of statistical averages (the law of mass action) at each step. A number of interesting questions arise in the mathematical analysis of these dynamical systems. In particular, one of the most important questions one can ask about the limiting pool of nucleic acids is the following: Under what conditions on the individual affinities of each nucleic acid for each target component does the dynamical system have a global attractor consisting of a single point? That is, when is the concentration distribution of the limiting pool of nucleic acids independent of the concentrations of the individual nucleic acids in the initial pool, assuming that all nucleic acids are initially present in the initial pool? The paper constitutes a summary of our theoretical and numerical work on these questions, carried out in some detail in [9, 11, 13].