Divergence Involving Global Regulatory Gene Mutations in an Escherichia coli Population Evolving under Phosphate Limitation

Many of the important changes in evolution are regulatory in nature. Sequenced bacterial genomes point to flexibility in regulatory circuits but we do not know how regulation is remodeled in evolving bacteria. Here, we study the regulatory changes that emerge in populations evolving under controlled conditions during experimental evolution of Escherichia coli in a phosphate-limited chemostat culture. Genomes were sequenced from five clones with different combinations of phenotypic properties that coexisted in a population after 37 days. Each of the distinct isolates contained a different mutation in 1 of 3 highly pleiotropic regulatory genes (hfq, spoT, or rpoS). The mutations resulted in dissimilar proteomic changes, consistent with the documented effects of hfq, spoT, and rpoS mutations. The different mutations do share a common benefit, however, in that the mutations each redirect cellular resources away from stress responses that are redundant in a constant selection environment. The hfq mutation lowers several individual stress responses as well the small RNA-dependent activation of rpoS translation and hence general stress resistance. The spoT mutation reduces ppGpp levels, decreasing the stringent response as well as rpoS expression. The mutations in and upstream of rpoS resulted in partial or complete loss of general stress resistance. Our observations suggest that the degeneracy at the core of bacterial stress regulation provides alternative solutions to a common evolutionary challenge. These results can explain phenotypic divergence in a constant environment and also how evolutionary jumps and adaptive radiations involve altered gene regulation.

Australian Research Council

Australian Research Council (ARC)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-Brazil)

National Natural Science Foundation of China (NSFC)[30530010]

National Natural Science Foundation of China (NSFC)

National Natural Science Foundation of China (NSFC)[30870070]

National Natural Science Foundation of China (NSFC)

National Natural Science Foundation of China (NSFC)

National Natural Science Foundation of China (NSFC)[30870078]

National Natural Science Foundation of China (NSFC)

National Natural Science Foundation of China (NSFC)[30771175]

Chinese National Science Fund for Distinguished Young Scholars

Chinese National Science Fund for Distinguished Young Scholars[30788001]

National 863 Program of China[2006AA020703]

National 863 Program of China

National 863 Program of China

National 863 Program of China[2006AA06Z409]

National 973 Program of China[2009CB522603]

National 973 Program of China

National Key Programs for Infectious Diseases of China

National Key Programs for Infectious Diseases of China[2008ZX1004-002]

National Key Programs for Infectious Diseases of China

National Key Programs for Infectious Diseases of China[2008ZX1004-009]

National Key Programs for Infectious Diseases of China

National Key Programs for Infectious Diseases of China[2009ZX10004-108]