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

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Dyer, Naomi A. and Lucas, Eric R. and Nagi, Sanjay C. and McDermott, Daniel P. and Brenas, Jon H. and Miles, Alistair and Clarkson, Chris S. and Mawejje, Henry D. and Wilding, Craig S. and Halfon, Marc S. and Asma, Hasiba and Heinz, Eva and Donnelly, Martin J. (2024) Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele-specific expression. Proceedings of the Royal Society B: Biological Sciences, 291 (2031). 20241142. ISSN 0962-8452 (https://doi.org/10.1098/rspb.2024.1142)

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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 cis, by regulatory sequences on the same chromosome, and by trans acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in cis-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb-resistant and susceptible Anopheles gambiae strains to identify cis-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 cis-regulation is an important mechanism of gene expression regulation in A. gambiae. The genes showing ASE included a higher proportion of Anopheles-specific genes on average younger than genes with balanced allelic expression.

ORCID iDs

Dyer, Naomi A., Lucas, Eric R., Nagi, Sanjay C., McDermott, Daniel P., Brenas, Jon H., Miles, Alistair, Clarkson, Chris S., Mawejje, Henry D., Wilding, Craig S., Halfon, Marc S., Asma, Hasiba, Heinz, Eva ORCID logoORCID: https://orcid.org/0000-0003-4413-3756 and Donnelly, Martin J.;
CORE (COnnecting REpositories)