Experimental evolution of cellular response networks in yeast

Organisms respond to environmental changes using complex signaling networks, whose evolution has been studied by comparing their structure and function in related organisms. We complemented this approach by using experimental evolution in Saccharomyces cerevisiae to explore how existing response networks change under selection. We selected for cell cycle arrest in response to an environmental change by alternating between an environment that favors cell proliferation and one that contains high salt (0.5 M NaCl) and hydroxyurea, a replication inhibitor that kills a genetically engineered ancestor if it attempts DNA replication. This selection yielded strains that arrest division in high NaCl. Causal mutations were identified by whole-genome sequencing and confirmed by genetic reconstruction.