Dynamical Analysis of Gene Networks Requires Both mRNA and Protein Expression Information

One of the important goals of biology is to understand the relationship between DNA sequence information and nonlinear cellular responses. This relationship is central to the ability to effectively engineer cellular phenotypes, pathways, and characteristics. Expression arrays for monitoring total gene expression based on mRNA can provide quantitative insight into which gene or genes are on or off; but this information is insufficient to fully predict dynamic biological phenomena. Using nonlinear stability analysis we show that a combination of gene expression information at the message level and at the protein level is required to describe even simple models of gene networks. To help illustrate the need for such information we consider a mechanistic model for circadian rhythmicity which shows agreement with experimental observations when protein and mRNA information are included and we propose a framework for acquiring and analyzing experimental and mathematically derived information about gene networks. (C) 1999 Academic Press