RT Journal Article SR Electronic T1 The Onset of Evolutionary Stalling and the Limit on the Power of Natural Selection to Improve a Cellular Module JF bioRxiv FD Cold Spring Harbor Laboratory SP 850644 DO 10.1101/850644 A1 Sandeep Venkataram A1 Ross Monasky A1 Shohreh H Sikaroodi A1 Sergey Kryazhimskiy A1 Betül Kaçar YR 2019 UL http://biorxiv.org/content/early/2019/12/13/850644.abstract AB Cells consist of molecular modules which perform vital biological functions. Modules are key units of adaptive evolution because organismal fitness depends on their performance. Yet, our understanding of adaptive evolution at the level of modules is limited. Theory predicts that in rapidly evolving populations, such as those of many microbes, natural selection focuses on improving one or a few modules at a time and its focus shifts to other modules as adaptation continues. Such shifts have never been directly observed, their timescale is unknown and the extent to which they limit the power of natural selection to improve any particular module is unclear. Here, we empirically characterize how natural selection improves the translation machinery (TM), one of the most essential cellular modules. To this end, we experimentally evolved populations of Escherichia coli with genetically perturbed TMs for 1,000 generations. Populations with different TMs embarked on statistically distinct adaptive trajectories. Yet, in all genetic backgrounds, the focus of natural selection shifted away from the TM before its performance was fully restored. Our results show that shifts in the focus of selection can occur on time scales comparable to those of environmental fluctuations. Variability in selection pressures can delay the resumption of adaptation in stalled modules, which would make it difficult for evolution to fully optimize even essential modules.