Evolutionary stalling and a limit on the power of natural selection to improve a cellular module

Sandeep Venkataram, Ross Monasky, Shohreh H. Sikaroodi, Sergey Kryazhimskiy, Betul Kacar

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Cells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations of Escherichia coli with genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.

Original languageEnglish (US)
Pages (from-to)18582-18590
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 4 2020


  • Adaptation
  • Experimental evolution
  • Translation

ASJC Scopus subject areas

  • General


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