The Selective Cause of an Ancient Adaptation
Science online 13 January 2005Guoping Zhu 1, G. Brian Golding 2, Antony M. Dean 3*
Phylogenetic analysis reveals that NADP use by prokaryotic isocitrate dehydrogenase arose around the time eukaryotic mitochondria first appeared, some 3.5 billion years ago. We replaced the wildtype gene encoding the NADP-dependent isocitrate dehydrogenase of Escherichia coli by an engineered one possessing the ancestral NAD-dependent phenotype. The engineered enzyme is disfavored during competition for acetate. The selection intensifies in genetic backgrounds where other sources of reduced NADP have been removed. A survey of sequenced prokaryotic genomes reveals that those encoding isocitrate lyase, which is essential for growth on acetate, always have an NADP-dependent isocitrate dehydrogenase. Those with only an NAD-dependent isocitrate dehydrogenase never have isocitrate lyase. Hence, the NADP-dependence of prokaryotic isocitrate dehydrogenase is an ancient adaptation to anabolic demand for reduced NADP during growth on acetate.
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