Evidence map›Paper›PMID 23798664›Full record

ArticleRNA (New York, N.Y.)2013

Synthetic shuffling and in vitro selection reveal the rugged adaptive fitness landscape of a kinase ribozyme.

Edward A Curtis, David P Bartel

Abstract read
In one paragraph

Article in RNA (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Article
  2. Article
  3. Pushing the Limits of Nucleic Acid Function.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022
    Review
  4. Article
  5. Supernova: A Deoxyribozyme that Catalyzes a Chemiluminescent Reaction.Angewandte Chemie (International ed. in English) · 2022
    Article
  6. Single-round deoxyribozyme discovery.Nucleic acids research · 2021
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Information theory, evolutionary innovations and evolvability.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Article
  15. Article
  16. Sex in a test tube: testing the benefits of in vitro recombination.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016
    Review
  17. High-Throughput Mutational Analysis of a Twister Ribozyme.Angewandte Chemie (International ed. in English) · 2016
    Article
  18. Review
  19. Fitness Landscapes of Functional RNAs.Life (Basel, Switzerland) · 2015
    Review
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

2 authors.

Edward A CurtisWhitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
David P Bartel

Funding

RNA CONFORMATION AND CATALYSISR01GM061835 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI BARTEL, DAVID P · 2000 to 2008
$2.5M
RNA Conformation and CatalysisR37GM061835 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI BARTEL, DAVID P · 2011 to 2016
$2.3M
Howard Hughes Medical InstituteNIGMS NIH HHS GM061835NIGMS NIH HHS R01 GM061835NIGMS NIH HHS R37 GM061835
6 · The paper itself

Abstract

The relationship between genotype and phenotype is often described as an adaptive fitness landscape. In this study, we used a combination of recombination, in vitro selection, and comparative sequence analysis to characterize the fitness landscape of a previously isolated kinase ribozyme. Point mutations present in improved variants of this ribozyme were recombined in vitro in more than 10(14) different arrangements using synthetic shuffling, and active variants were isolated by in vitro selection. Mutual information analysis of 65 recombinant ribozymes isolated in the selection revealed a rugged fitness landscape in which approximately one-third of the 91 pairs of positions analyzed showed evidence of correlation. Pairs of correlated positions overlapped to form densely connected networks, and groups of maximally connected nucleotides occurred significantly more often in these networks than they did in randomized control networks with the same number of links. The activity of the most efficient recombinant ribozyme isolated from the synthetically shuffled pool was 30-fold greater than that of any of the ribozymes used to build it, which indicates that synthetic shuffling can be a rich source of ribozyme variants with improved properties.

Indexed as

Base SequenceDirected Molecular EvolutionKineticsMolecular Sequence DataMutagenesis, Site-DirectedNucleic Acid ConformationRecombination, GeneticRNA, CatalyticThermodynamicsRNA, Catalyticfitness landscapein vitro selectionribozymesynthetic recombinationsynthetic shuffling

Identifiers

PMID23798664
PMCPMC3708531

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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.