Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution
Pleiotropic regulatory mutations affect diverse cellular processes, posing a challenge to our understanding of genotype-phenotype relationships across multiple biological scales. Adaptive laboratory evolution (ALE) allows for such mutations to be found and characterized in the context of clear selection pressures. Here, several ALE-selected single-mutation variants in RNA polymerase (RNAP) of Escherichia coli are detailed using an integrated multi-scale experimental and computational approach. While these mutations increase cellular growth rates in steady environments, they reduce tolerance to stress and environmental fluctuations. We detail structural changes in the RNAP that rewire the transcriptional machinery to rebalance proteome and energy allocation toward growth and away from several hedging and stress functions. We find that while these mutations occur in diverse locations in the RNAP, they share a common adaptive mechanism. In turn, these findings highlight the resource allocation trade-offs organisms face and suggest how the structure of the regulatory network enhances evolvability.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1353268
- Alternate ID(s):
- OSTI ID: 1543519
- Journal Information:
- Cell Systems, Journal Name: Cell Systems Vol. 2 Journal Issue: 4; ISSN 2405-4712
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- Niger
- Language:
- English
Web of Science
Similar Records
Mutation network-based understanding of pleiotropic and epistatic mutational behavior of Enterococcus faecalis FMN-dependent azoreductase
GENETIC MODIFICATION OF GIBBERELLIC ACID SIGNALING TO PROMOTE CARBON SEQUESTRATION IN TREE ROOTS AND STEMS