Epistasis Map of the Functional Architecture of Bacterial Systems
Quantitative Genome-Wide Genetic Interaction Screens Reveal the Global Functional Organization of Soluble Protein Complexes in Escherichia coli
Babu et al., 2014
Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI) screens can provide insights into the biological role(s) of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screens in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected crosstalk, including, amongst others, new components required for the biogenesis of iron-sulphur and ribosome integrity and the interplay between molecular chaperones and proteases. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.