Twenty-five Years of Delila and Molecular Information Theory

Abstract

A brief personal history is given about how information theory can be applied to binding sites of genetic control molecules on nucleic acids. The primary example used is ribosome binding sites in Escherichia coli. Once the sites are aligned, the information needed to describe the sites can be computed using Claude Shannon's method. This is displayed by a computer graphic called a sequence logo. The logo represents an average binding site, and the mathematics easily allows one to determine the components of this average. That is, given a set of binding sites, the information for individual binding sites can also be computed. One can go further and predict the information of sites that are not in the original data set. Information theory also allows one to model the flexibility of ribosome binding sites, and this led us to a simple model for ribosome translational initiation in which the molecular components fit together only when the ribosome is at a good ribosome binding site. Since information theory is general, the same mathematics applies to human splice junctions, where we can predict the effect of sequence changes that cause human genetic diseases and cancer. The second example given is the Pribnow 'box' which, when viewed by the information theory method, reveals a mechanism for initiation of both transcription and DNA replication. Replication, transcription, splicing, and translation into protein represent the central dogma, so these examples show how molecular information theory is contributing to our knowledge of basic biology.