Paper detail

A unified formal framework for developmental andevolutionary change in gene regulatory network models

The two most fundamental processes describing change in biology, development and evolu-tion, occur over drastically different timescales, difficult to reconcile within a unified framework. Development involves temporal sequences of cell states controlled by hierarchies of regulatory structures. It occurs over the lifetime of a single individual, and is associated to the gene expression level change of a given genotype. Evolution, by contrast entails genotypic change through the acquisition/loss of genes and changes in the network topology of interactions among genes. It involves the emergence of new, environmentally selected phenotypes over the lifetimes of many individuals. Here we present a model of regulatory network evolution that accounts for both timescales. We extend the framework of Boolean models of gene regulatory networks (GRN)-currently only applicable to describing development to include evolutionary processes. As opposed to one-to-one maps to specific attractors, we identify the phenotypes of the cells as the relevant macrostates of the GRN. A phenotype may now correspond to multiple attractors, and its formal definition no longer requires a fixed size for the genotype. This opens the possibility for a quantitative study of the phenotypic change of a genotype, which is itself changing over evolutionary timescales. We show how the realization of specific phenotypes can be controlled by gene duplication events (used here as an archetypal evolutionary event able to change the genotype), and how successive events of gene duplication lead to new regulatory structures via selection. At the same time, we show that our generalized framework does not inhibit network controllability and the possibility for network control theory to describe epigenetic signaling during development.