Evidence map›Paper›PMID 25865270›Full record

ArticleMolecular ecology2015

Contemporary evolution of resistance at the major insecticide target site gene Ace-1 by mutation and copy number variation in the malaria mosquito Anopheles gambiae.

David Weetman, Sara N Mitchell, Craig S Wilding, Daniel P Birks, Alexander E Yawson, John Essandoh, Henry D Mawejje, Luc S Djogbenou, Keith Steen, Emily J Rippon and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular ecology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 81 citations in OpenAlex.

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  9. Mechanisms of transcriptional regulation inProceedings. Biological sciences · 2024
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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

14 authors at 9 institutions in 6 countries.

David WeetmanDepartment of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Sara N MitchellDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Craig S WildingSchool of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool, UK.
Daniel P BirksDepartment of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Alexander E YawsonBiotechnology and Nuclear Agriculture Research Institute, Ghana Atomic Energy Commission, Kwabenya, Accra, Ghana.
John EssandohDepartment of Wildlife and Entomology, University of Cape Coast, Cape Coast, Ghana.
Henry D MawejjeInfectious Diseases Research Collaboration, Kampala, Uganda.
Luc S DjogbenouInstitut Regional de Sante Publique de Ouidah, Ouidah, Benin.
Keith SteenDepartment of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Emily J RipponDepartment of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Christopher S ClarksonDepartment of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Stuart G FieldDepartment of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, CO, USA.
Daniel J RigdenInstitute of Integrative Biology, University of Liverpool, Liverpool, UK.
Martin J DonnellyDepartment of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
Liverpool School of Tropical Medicine · GBColorado State University · USGhana Atomic Energy Commission · GHHarvard University · USInfectious Diseases Research Collaboration · UGInstitut National de Santé Publique · TNLiverpool John Moores University · GBUniversity of Cape Coast · GHUniversity of Liverpool · GB

Funding

Transmission ProjectU19AI089674 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHEW G DORSEY, MOSES Robert KAMYA · 2010 to 2026
$29.3M
Development of a Field Applicable Screening Tool (FAST) kit for detecting resistaR01AI082734 · NIAID · TMLIVERPOOL SCHOOL OF TROPICAL MEDICINE · PI DONNELLY, MARTIN JAMES · 2009 to 2013
$1.6M
Biotechnology and Biological Sciences Research CouncilNIAID NIH HHS R01 AI082734NIAID NIH HHS R01AI082734NIAID NIH HHS U19 AI089674Wellcome TrustWellcome Trust WT093755
6 · The paper itself

Abstract

Functionally constrained genes are ideal insecticide targets because disruption is often fatal, and resistance mutations are typically costly. Synaptic acetylcholinesterase (AChE) is an essential neurotransmission enzyme targeted by insecticides used increasingly in malaria control. In Anopheles and Culex mosquitoes, a glycine-serine substitution at codon 119 of the Ace-1 gene confers both resistance and fitness costs, especially for 119S/S homozygotes. G119S in Anopheles gambiae from Accra (Ghana) is strongly associated with resistance, and, despite expectations of cost, resistant 119S alleles are increasing significantly in frequency. Sequencing of Accra females detected only a single Ace-1 119S haplotype, whereas 119G diversity was high overall but very low at non-synonymous sites, evidence of strong purifying selection driven by functional constraint. Flanking microsatellites showed reduced diversity, elevated linkage disequilibrium and high differentiation of 119S, relative to 119G homozygotes across up to two megabases of the genome. Yet these signals of selection were inconsistent and sometimes weak tens of kilobases from Ace-1. This unexpected finding is attributable to apparently ubiquitous amplification of 119S alleles as part of a large copy number variant (CNV) far exceeding the size of the Ace-1 gene, whereas 119G alleles were unduplicated. Ace-1 CNV was detectable in archived samples collected when the 119S allele was rare in Ghana. Multicopy amplification of resistant alleles has not been observed previously and is likely to underpin the recent increase in 119S frequency. The large CNV compromised localization of the strong selective sweep around Ace-1, emphasizing the need to integrate CNV analysis into genome scans for selection.

Indexed as

DNA Copy Number VariationsEvolution, MolecularAcetylcholinesteraseAllelesAnimalsAnophelesFemaleGenes, InsectGenotypeGhanaHaplotypesInsecticide ResistanceLinkage DisequilibriumMicrosatellite RepeatsMolecular Sequence DataSequence Analysis, DNAAcetylcholinesteraseAce-1 G119SAcetylcholinesterasegene duplicationmalaria mosquitopurifying selection

Identifiers

PMID25865270
PMCPMC4447564
OpenAlexW2105640468

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.