Bernhard Palsson

Title: Galletti Professor of Bioengineering
Office: University of California, San Diego

Calculation of Proteome Allocation is Enabled by Genome-Scale Models

Abstract: A fundamental problem of systems biology has been to understand how cellular proteome allocation strategies affect fitness under varying environments and genetic backgrounds. Recently, integrated genome-scale models of metabolism and gene expression (ME-Models) have been developed, which account for 80% of the Escherichia coli proteome by mass. These ME-Models enable calculation of proteome allocation and its phenotypic effects at the genome-scale. Using a ME-Model of E. coli, we identified a core proteome consisting of 356 gene products (44% of E. coli proteome mass), which was always expressed under 333 simulated growth conditions. The core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in non-differentially expressed genes, and depleted in differentially expressed genes. Compared to the non-core, core gene expression levels are also similar across genetic backgrounds and exhibit significantly more complex transcriptional and post-transcriptional regulatory features. Future ME-Model developments include expanding model scope to the remaining 20% of proteome mass, and integration of ME with transcriptional regulation. These expansions will further enable systems-level investigation into the cellular control strategies that have evolved for proteome allocation under changing environments and stress conditions.