Hierarchical evolution of the bacterial sporulation network

Genome sequencing of multiple species makes it possible to understand the main principles behind the evolution of developmental regulatory networks. It is especially interesting to analyze the evolution of well-defined model systems in which conservation patterns can be directly correlated with the functional roles of various network components. Endospore formation (sporulation), extensively studied in Bacillus subtilis, is driven by such a model bacterial network of cellular development and differentiation. In this review, we analyze the evolution of the sporulation network in multiple endospore-forming bacteria. Importantly, the network evolution is not random but primarily follows the hierarchical organization and functional logic of the sporulation process. Specifically, the sporulation sigma factors and the master regulator of sporulation, Spo0A, are conserved in all considered spore-formers. The sequential activation of these global regulators is also strongly conserved. The feed-forward loops, which are likely used to fine-tune waves of gene expression within regulatory modules, show an intermediate level of conservation. These loops are less conserved than the sigma factors but significantly more than the structural sporulation genes, which form the lowest level in the functional and evolutionary hierarchy of the sporulation network. Interestingly, in spore-forming bacteria, gene regulation is more conserved than gene presence for sporulation genes, while the opposite is true for non-sporulation genes. The observed patterns suggest that, by understanding the functional organization of a developmental network in a model organism, it is possible to understand the logic behind the evolution of this network in multiple related species.