Evidence map›Paper›PMID 27135538›Full record

ArticleCell systems2016

Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution.

Jose Utrilla, Edward J O'Brien, Ke Chen, Douglas McCloskey, Jacky Cheung, Harris Wang, Dagoberto Armenta-Medina, Adam M Feist, Bernhard O Palsson

Abstract read
In one paragraph

Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

68 citing papers in PubMed.

  1. Review
  2. S267P mutation of OxyR regulator inSynthetic and systems biotechnology · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Evolution of pollutant biodegradation.Applied microbiology and biotechnology · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Convergent genetic adaptation ofFrontiers in molecular biosciences · 2024
    Article
  15. Article
  16. Article
  17. Development of heat-shock resistance inApplied and environmental microbiology · 2023
    Article
  18. Article
  19. Article
  20. Article

8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jose UtrillaDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, 62210 Cuernavaca, Morelos, México.
Edward J O'BrienDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
Ke ChenDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Douglas McCloskeyDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Jacky CheungDepartment of Systems Biology, Columbia University, New York, NY 10027, USA.
Harris WangDepartment of Systems Biology, Columbia University, New York, NY 10027, USA.
Dagoberto Armenta-MedinaDepartamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, UNAM, 62210 Cuernavaca, Morelos, Mexico.
Adam M FeistDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark.
Bernhard O PalssonDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: palsson@eng.ucsd.edu.

Funding

GENOMICALLY BASED MODELS FOR ANTIBIOTIC DEVELOPMENTR01GM057089 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 1998 to 2021
$6.9M
Functional Metagenomic Reprogramming of the Human Microbiome through Mobilome EngDP5OD009172 · OD · HARVARD MEDICAL SCHOOL · PI WANG, HARRIS H · 2011 to 2015
$2.0M
Multiscale Molecular Systems Biology: Reconstruction and Model OptimizationU01GM102098 · NIGMS · STANFORD UNIVERSITY · PI SAUNDERS, MICHAEL ALAN · 2012 to 2016
$1.8M
NIGMS NIH HHS R01 GM057089NIGMS NIH HHS U01 GM102098NIH HHS DP5 OD009172
6 · The paper itself

Abstract

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.

Indexed as

Point MutationAdaptation, PhysiologicalBiological EvolutionDNA-Directed RNA PolymerasesEscherichia coliEscherichia coli ProteinsEvolution, MolecularPhenotypeDNA-Directed RNA PolymerasesEscherichia coli Proteins

Identifiers

PMID27135538
PMCPMC4853925

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.