Evidence map›Paper›PMID 24732957›Full record

ArticleMolecular biology and evolution2014

Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance.

Nichola J Hawkins, Hans J Cools, Helge Sierotzki, Michael W Shaw, Wolfgang Knogge, Steven L Kelly, Diane E Kelly, Bart A Fraaije

Open access · bronzeAbstract read
In one paragraph

Article in Molecular biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
16.4field-weighted citation impact, top 1% of its field
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

43 citing papers in PubMed, 96 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Identification of Potent and Selective Inhibitors ofJournal of medicinal chemistry · 2024
    Article
  7. Review
  8. Review
  9. Drug-ResistantPathogens (Basel, Switzerland) · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Evidence for the Role ofInternational journal of molecular sciences · 2021
    Article
  15. Characterization ofApplied and environmental microbiology · 2021
    Article
  16. Review
  17. A Cyp51B Mutation Contributes to Azole Resistance inJournal of fungi (Basel, Switzerland) · 2020
    Article
  18. Article
  19. Review
  20. Pathogenomics and Management ofPathogens (Basel, Switzerland) · 2020
    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

8 authors at 5 institutions in 3 countries.

Nichola J HawkinsBiological Chemistry and Crop Protection, Rothamsted Research, Harpenden, Hertfordshire, United Kingdom.
Hans J CoolsBiological Chemistry and Crop Protection, Rothamsted Research, Harpenden, Hertfordshire, United Kingdom.
Helge SierotzkiResearch Biology, Syngenta Crop Protection, Basel, Switzerland.
Michael W ShawSchool of Agriculture, Policy and Development, University of Reading, Whiteknights, Reading, United Kingdom.
Wolfgang KnoggeDepartment of Stress and Developmental Biology, Leibniz Institute of Plant Biochemistry, Halle, Germany.
Steven L KellyInstitute of Life Science and College of Medicine, Swansea University, Swansea, United Kingdom.
Diane E KellyInstitute of Life Science and College of Medicine, Swansea University, Swansea, United Kingdom.
Bart A FraaijeBiological Chemistry and Crop Protection, Rothamsted Research, Harpenden, Hertfordshire, United Kingdom bart.fraaije@rothamsted.ac.uk.
Rothamsted Research · GBSwansea University · GBLeibniz Institute of Plant Biochemistry · DESyngenta (Switzerland) · CHUniversity of Reading · GB

Funding

Biotechnology and Biological Sciences Research Council
6 · The paper itself

Abstract

Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.

Indexed as

Drug Resistance, FungalAscomycotaAzolesCytochrome P-450 Enzyme SystemEvolution, MolecularFungal ProteinsFungicides, IndustrialHordeumPhylogenySelection, GeneticSequence Analysis, DNAAzolesCytochrome P-450 Enzyme SystemFungal ProteinsFungicides, Industrialfungicidesgene duplicationresistanceRhynchosporiumstanding variationtriazoles

Identifiers

PMID24732957
PMCPMC4069618
OpenAlexW2102332954

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.