RESUMO
Defining the gene products that play an essential role in an organism's functional repertoire is vital to understanding the system level organization of living cells. We used a genetic footprinting technique for a genome-wide assessment of genes required for robust aerobic growth of Escherichia coli in rich media. We identified 620 genes as essential and 3,126 genes as dispensable for growth under these conditions. Functional context analysis of these data allows individual functional assignments to be refined. Evolutionary context analysis demonstrates a significant tendency of essential E. coli genes to be preserved throughout the bacterial kingdom. Projection of these data over metabolic subsystems reveals topologic modules with essential and evolutionarily preserved enzymes with reduced capacity for error tolerance.
Assuntos
Pegada de DNA/métodos , Proteínas de Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Genoma Bacteriano , Aerobiose , Aminoácidos/biossíntese , Meios de Cultura , Elementos de DNA Transponíveis , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Evolução Molecular , Regulação Bacteriana da Expressão Gênica , Genes Essenciais , Mutagênese Insercional , FilogeniaRESUMO
Spatially or chemically isolated functional modules composed of several cellular components and carrying discrete functions are considered fundamental building blocks of cellular organization, but their presence in highly integrated biochemical networks lacks quantitative support. Here, we show that the metabolic networks of 43 distinct organisms are organized into many small, highly connected topologic modules that combine in a hierarchical manner into larger, less cohesive units, with their number and degree of clustering following a power law. Within Escherichia coli, the uncovered hierarchical modularity closely overlaps with known metabolic functions. The identified network architecture may be generic to system-level cellular organization.