MBE Advance Access published online on September 19, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm204
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Research Article |
Multicopy Suppression Underpins Metabolic Evolvability
Department of Biochemistry, Center for Fundamental and Applied Molecular Evolution, Emory University, Atlanta, Georgia 30322, USA
Correspondence: Assoc. Prof. Ichiro Matsumura, Department of Biochemistry, Emory University, 1510 Clifton Rd, Atlanta, GA 30322, USA. Tel. +1 (404) 727-5625; fax +1 (404) 727-3452; email imatsum{at}emory.edu.
Received for publication July 4, 2007. Revision received August 14, 2007. Accepted for publication September 16, 2007.
Our understanding of the origins of new metabolic functions is based upon anecdotal genetic and biochemical evidence. Some auxotrophies can be suppressed by over-expressing substrate ambiguous enzymes (i.e. those that catalyze the same chemical transformation on different substrates). Other enzymes exhibit weak but detectable catalytic promiscuity in vitro (i.e. they catalyze different transformations on similar substrates). Cells adapt to novel environments through the evolution of these secondary activities, but neither their chemical natures nor their frequencies of occurrence have been characterized en bloc. Here, we systematically identified multi-functional genes within the Escherichia coli genome. We screened 104 single-gene knockout strains and discovered that many (20%) of these auxotrophs were rescued by the over-expression of at least one non-cognate E. coli gene. The deleted gene and its suppressor were generally unrelated, suggesting that promiscuity is a product of contingency. This genome-wide survey demonstrates that multi-functional genes are common, and illustrates the mechanistic diversity by which their products enhance metabolic robustness and evolvability.
Key Words: Catalytic promiscuity • directed evolution • multicopy suppression • substrate ambiguity