A Theoretical Systems Biology Analysis Suggests Gene-Environment Interaction Effects are Common at the Most Basic Levels of Biological Organization

There is much current interest in how biological systems respond to environmental changes. In this article, we address this question from a theoretical systems biology perspective. Specifically, we examine linear enzyme pathways, including all processes from transcription to enzyme action, and incorporating biologically-realistic negative feedback in the form of competitive inhibition. We investigated how steady state biomarker concentrations changed in response to variable rates of precursor material inflow across genetically variable systems, with alleles conferring different expression rates. We observed a non- equivalence of response across these systems, implying a gene-environment interaction. Furthermore, we observed that total variance in populations of systems increased dramatically in response to increased precursor material influx. These results imply that gene-environment interaction effects are likely to occur at the most basic levels of biological organization, even in the presence of negative feedback.