Evidence map›Paper›PMID 22532576›Full record

ArticleMolecular biology and evolution2012

Slow fitness recovery in a codon-modified viral genome.

J J Bull, I J Molineux, C O Wilke

Abstract read
In one paragraph

Article in Molecular biology and evolution, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing 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

39 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  6. Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Transmissible Viral Vaccines.Trends in microbiology · 2018
    Review
  17. Article
  18. Arresting Evolution.Trends in genetics : TIG · 2017
    Review
  19. Article
  20. Article
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

3 authors.

J J BullThe Institute for Cellular and Molecular Biology, The University of Texas at Austin. bull@mail.utexas.edu
I J Molineux
C O Wilke

Funding

The biophysical basis of translational selectionR01GM088344 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BARRICK, JEFFREY EVAN, WILKE, CLAUS O · 2009 to 2023
$3.5M
Experimental viral evolution at high mutation rateR01GM057756 · NIGMS · UNIVERSITY OF TEXAS AUSTIN · PI BULL, JAMES J · 1998 to 2013
$2.9M
NIGMS NIH HHS R01 GM057756NIGMS NIH HHS R01 GM088344
6 · The paper itself

Abstract

Extensive synonymous codon modification of viral genomes appears to be an effective way of attenuating strains for use as live vaccines. An assumption of this method is that codon changes have individually small effects, such that codon-attenuated viruses will be slow to evolve back to high fitness (and thus to high virulence). The major capsid gene of the bacterial virus T7 was modified to have varying levels of suboptimal synonymous codons in different constructs, and fitnesses declined linearly with the number of changes. Adaptation of the most extreme design, with 182 codon changes, resulted in a slow fitness recovery by standards of previous experimental evolution with this virus, although fitness effects of substitutions were higher than expected from the average effect of an engineered codon modification. Molecular evolution during recovery was modest, and changes evolved both within the modified gene and outside it. Some changes within the modified gene evolved in parallel across replicates, but with no obvious explanation. Overall, the study supports the premise that codon-modified viruses recover fitness slowly, although the evolution is substantially more rapid than expected from the design principle.

Indexed as

Genetic FitnessAdaptation, BiologicalBacteriophage T7Base SequenceCodonEvolution, MolecularGenome, ViralNucleotidesCodonNucleotides

Identifiers

PMID22532576
PMCPMC3457771

What OpenQuestion holds

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Registered trials

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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.