Mutations that improve efficiency of a weak-link enzyme are rare compared to adaptive mutations elsewhere in the genome.
New enzymes often evolve by gene amplification and divergence. Previous experimental studies have followed the evolutionary trajectory of an amplified gene, but have not considered mutations elsewhere in the genome when fitness is limited by an evolving gene. We have evolved a strain of Escherichia coli in which a secondary promiscuous activity has been recruited to serve an essential function. The gene encoding the 'weak-link' enzyme amplified in all eight populations, but mutations improving the newly needed activity occurred in only one. Most adaptive mutations occurred elsewhere in the genome. Some mutations increase expression of the enzyme upstream of the weak-link enzyme, pushing material through the dysfunctional metabolic pathway. Others enhance production of a co-substrate for a downstream enzyme, thereby pulling material through the pathway. Most of these latter mutations are detrimental in wild-type E. coli, and thus would require reversion or compensation once a sufficient new activity has evolved.
['Morgenthaler|Andrew B|AB|0000-0003-3822-0212', 'Kinney|Wallis R|WR|', 'Ebmeier|Christopher C|CC|0000-0001-7940-6190', 'Walsh|Corinne M|CM|', 'Snyder|Daniel J|DJ|', 'Cooper|Vaughn S|VS|0000-0001-7726-0765', 'Old|William M|WM|', 'Copley|Shelley D|SD|0000-0001-9727-7919']
D000220:Adaptation, Biological D004798:Enzymes D004926:Escherichia coli D056084:Genetic Fitness D016680:Genome, Bacterial D053858:Metabolic Networks and Pathways D009154:Mutation
genomics amplification and divergence promiscuity E. coli ProA evolution evolutionary biology genetics