Mechanisms of transcriptional regulation in <i>Anopheles gambiae</i> revealed by allele-specific expression

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in <i>cis</i>, by regulatory sequences on the same chromosome, and by <i>trans</i> acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in <i>cis</i>-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb-resistant and susceptible <i>Anopheles gambiae</i> strains to identify <i>cis</i>-regulated genes that might be responsible for the resistant phenotype using RNAseq, and CRM sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele-specific expression (ASE) in hybrids of insecticide susceptible and resistant strains, suggesting <i>cis</i>-regulation is an important mechanism of gene expression regulation in <i>A. gambiae</i>. The genes showing ASE included a higher proportion of <i>Anopheles</i>-specific genes on average younger than genes with balanced allelic expression.

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Publication Details

Journal
Proceedings of the Royal Society B Biological Sciences
Published
2024-09-01
DOI
https://doi.org/10.1098/rspb.2024.1142
Citations
2
Primary Topic
Insect Resistance and Genetics
Type
article
Field-Weighted Citation Impact
0.47

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article

Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele-specific expression

Henry Mawejje, Eric R. Lucas, Martin J. Donnelly, Eva Heinz et al.
2 citations
Proceedings of the Royal Society B Biological Sciences
Insect Resistance and Genetics
0.47
article

Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele-specific expression

Henry Mawejje, Eric R. Lucas, Martin J. Donnelly, Eva Heinz, Marc S. Halfon, Naomi A. Dyer, Craig S. Wilding, Daniel P. McDermott, Chris S. Clarkson, Alistair Miles, Sanjay C. Nagi, Hasiba Asma, Jon Haël Brenas
article en
2 citations

Abstract

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in <i>cis</i>, by regulatory sequences on the same chromosome, and by <i>trans</i> acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in <i>cis</i>-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb-resistant and susceptible <i>Anopheles gambiae</i> strains to identify <i>cis</i>-regulated genes that might be responsible for the resistant phenotype using RNAseq, and CRM sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele-specific expression (ASE) in hybrids of insecticide susceptible and resistant strains, suggesting <i>cis</i>-regulation is an important mechanism of gene expression regulation in <i>A. gambiae</i>. The genes showing ASE included a higher proportion of <i>Anopheles</i>-specific genes on average younger than genes with balanced allelic expression.

Proceedings of the Royal Society B Biological SciencesVol. 291(2031)
University of Strathclyde (GB), Liverpool School of Tropical Medicine (GB), Wellcome Sanger Institute (GB), Infectious Diseases Research Collaboration (UG), Liverpool John Moores University (GB), University at Buffalo, State University of New York (US)
Bill and Melinda Gates Foundation, Broad Institute, Liverpool School of Tropical Medicine, Royal Society, European Commission, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute of Allergy and Infectious Diseases, European and Developing Countries Clinical Trials Partnership
Good health and well-being
Openalex Percentile: Top 35%
Insect Resistance and Genetics
0.47
DOIOpen Access PDFOpenAlex
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