The evolution of heterogeneities altered by mutational robustness, gene expression noise and bottlenecks in gene regulatory networks.

Abstract

Intra-population heterogeneity is commonly observed in natural and cellular populations and has profound influence on their evolution. For example, intra-tumor heterogeneity is prevalent in most tumor types and can result in the failure of tumor therapy. However, the evolutionary process of heterogeneity remains poorly characterized at both genotypic and phenotypic level. Here we study the evolution of intra-population heterogeneities of gene regulatory networks (GRN), in particular mutational robustness and gene expression noise as contributors to the development of heterogeneities. By in silico simulations, it was found that the impact of these factors on GRN can, under certain conditions, promote phenotypic heterogeneity. We also studied the effect of population bottlenecks on the evolution of GRN. When the GRN population passes through such bottlenecks, neither mutational robustness nor population fitness was observed to be substantially altered. Interestingly, however, we did detect a significant increase in the number of potential "generator" genes which can substantially induce population fitness, when stimulated by mutational hits.