TY - JOUR
T1 - Evolutionary stalling and a limit on the power of natural selection to improve a cellular module
AU - Venkataram, Sandeep
AU - Monasky, Ross
AU - Sikaroodi, Shohreh H.
AU - Kryazhimskiy, Sergey
AU - Kacar, Betul
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank members of the Kryazhimskiy and Kacar groups, Joanna Masel, Ryan Gutenkunst, Suparna Sanyal, Grant Kinsler, Justin Meyer, and Lin Chao for input and feedback. We thank Alex Ples¸a, Divjot Kaur, Emily Peñaherrera, Kevin Longoria, Lesly Villarejo, Alena Martsul, and Sarah Ardell for laboratory assistance. We thank Huanyu Kuo for the analysis of growth curve data. We thank Eva Garmendia for providing the recombineering plasmids and Georg Rieckh for providing the resistance marker plasmids. We thank Benjamin Good for help with his genome sequencing data analysis pipeline. We thank Kristen Jepsen and the UCSD Institute for Genomic Medicine for sequencing services and the San Diego Supercomputing Center for providing the computational environment. B.K. acknowledges the support by the John Templeton Foundation (grants 58562 and 61239), the NASA Exobiology and Evolutionary Biology Program (grant H006201406), and the NASA Astrobiology Institute (grant NNA17BB05A). S.K. acknowledges the support by Burroughs Wellcome Fund Career Award at the Scientific Interface (grant 1010719.01), the Alfred P. Sloan Foundation (grant FG-2017-9227), and the Hellman Foundation.
Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/4
Y1 - 2020/8/4
N2 - 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.
AB - 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.
KW - Adaptation
KW - Experimental evolution
KW - Translation
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U2 - 10.1073/pnas.1921881117
DO - 10.1073/pnas.1921881117
M3 - Article
C2 - 32680961
AN - SCOPUS:85089165927
VL - 117
SP - 18582
EP - 18590
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 31
ER -