The Selective Cause of an Ancient Adaptation
Guoping Zhu,1*
G. Brian Golding,3
Antony M. Dean1,2
Phylogenetic analysis reveals that the use of nicotinamide adenine dinucleotide phosphate (NADP) by prokaryotic isocitrate dehydrogenase (IDH) arose around the time eukaryotic mitochondria first appeared, about 3.5 billion years ago. We replaced the wild-type gene that encodes the NADP-dependent IDH of Escherichia coli with an engineered gene that possesses 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 genomes that encode isocitrate lyase, which is essential for growth on acetate, always have an NADP-dependent IDH. Those with only an NAD-dependent IDH never have isocitrate lyase. Hence, the NADP dependence of prokaryotic IDH is an ancient adaptation to anabolic demand for reduced NADP during growth on acetate.
1 BioTechnology Institute, University of Minnesota, St. Paul, MN 55108, USA.
2 Department of Ecology, Evolution, and Behavior, University of Minnesota, St. Paul, MN 55108, USA.
3 Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
* Present address: Department of Biology, Anhui Normal University, Wuhu 241000, People's Republic of China.
To whom correspondence should be addressed. E-mail: adean{at}biosci.umn.edu
