{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T16:31:57Z","timestamp":1793637117715,"version":"4.5.1"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TTU 03.705"],"award-info":[{"award-number":["TTU 03.705"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R015678\/1"],"award-info":[{"award-number":["MR\/R015678\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["NIAID R01-AI116811"],"award-info":[{"award-number":["NIAID R01-AI116811"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Malaria control faces challenges from widespread insecticide resistance in major <jats:italic>Anopheles<\/jats:italic> species. This study, employing a cross-species approach, integrates RNA-Sequencing, whole-genome sequencing, and microarray data to elucidate drivers of insecticide resistance in <jats:italic>Anopheles gambiae<\/jats:italic> complex and <jats:italic>An. funestus<\/jats:italic>. Here we show an inverse relationship between genetic diversity and gene expression, with highly expressed genes experiencing stronger purifying selection. Gene expression clusters physically in the genome, revealing potential coordinated regulation, and we find that highly over-expressed genes are associated with selective sweep loci. We identify known and novel candidate insecticide resistance genes, enriched for metabolic, cuticular, and behavioural functioning. We also present AnoExpress, a Python package, and an online interface for user-friendly exploration of resistance candidate expression. Despite millions of years of speciation, convergent gene expression responses to insecticidal selection pressures are observed across <jats:italic>Anopheles<\/jats:italic> species, providing crucial insights for malaria vector control.<\/jats:p>","DOI":"10.1038\/s42003-025-08221-6","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T10:04:52Z","timestamp":1747994692000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-8523","authenticated-orcid":false,"given":"Sanjay C.","family":"Nagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5708-4741","authenticated-orcid":false,"given":"Victoria A.","family":"Ingham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"8221_CR1","unstructured":"WHO. World Malaria Report (WHO, 2023)."},{"key":"8221_CR2","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nature15535","volume":"526","author":"S Bhatt","year":"2015","unstructured":"Bhatt, S. et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature 526, 207\u2013211 (2015).","journal-title":"Nature"},{"key":"8221_CR3","unstructured":"World Health Organization. WHA72 (World Health Organization, 2018)."},{"key":"8221_CR4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16090","volume":"5","author":"TS Churcher","year":"2016","unstructured":"Churcher, T. S., Lissenden, N., Griffin, J. T., Worrall, E. & Ranson, H. The impact of pyrethroid resistance on the efficacy and effectiveness of bednets for malaria control in Africa. Elife 5, e16090 (2016).","journal-title":"Elife"},{"key":"8221_CR5","doi-asserted-by":"publisher","first-page":"e103816","DOI":"10.1371\/journal.pone.0103816","volume":"9","author":"S Cornelie","year":"2014","unstructured":"Cornelie, S. et al. Salivary gland proteome analysis reveals modulation of anopheline Unique Proteins in Insensitive acetylcholinesterase resistant Anopheles gambiae mosquitoes. PLoS ONE 9, e103816 (2014).","journal-title":"PLoS ONE"},{"key":"8221_CR6","doi-asserted-by":"publisher","first-page":"246","DOI":"10.11646\/zootaxa.3619.3.2","volume":"3619","author":"M Coetzee","year":"2013","unstructured":"Coetzee, M. et al. Anopheles coluzzii and Anopheles amharicus, new members of the Anopheles gambiae complex. Zootaxa 3619, 246\u2013274 (2013).","journal-title":"Zootaxa"},{"key":"8221_CR7","doi-asserted-by":"crossref","unstructured":"Sinka, M. E. et al. The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic pr\u00e9cis. 3, 1\u201334 (2010).","DOI":"10.1186\/1756-3305-3-117"},{"key":"8221_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-017-1741-6","volume":"18","author":"D Guo","year":"2017","unstructured":"Guo, D. et al. ACE: an efficient and sensitive tool to detect insecticide resistance-associated mutations in insect acetylcholinesterase from RNA-Seq data. BMC Bioinform. 18, 330 (2017).","journal-title":"BMC Bioinform."},{"key":"8221_CR9","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1146\/annurev-ento-011118-112420","volume":"64","author":"JG Scott","year":"2019","unstructured":"Scott, J. G. Life and death at the voltage-sensitive sodium channel: evolution in response to insecticide use. Annu. Rev. Entomol. 64, 243\u2013257 (2019).","journal-title":"Annu. Rev. Entomol."},{"key":"8221_CR10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1146\/annurev-ento-070621-061328","volume":"67","author":"R Nauen","year":"2022","unstructured":"Nauen, R., Bass, C., Feyereisen, R. & Vontas, J. The role of cytochrome P450s in insect toxicology and resistance. Annu. Rev. Entomol. 67, 105\u2013124 (2022).","journal-title":"Annu. Rev. Entomol."},{"key":"8221_CR11","doi-asserted-by":"publisher","first-page":"5303","DOI":"10.1111\/mec.15845","volume":"30","author":"CS Clarkson","year":"2021","unstructured":"Clarkson, C. S. et al. The genetic architecture of target-site resistance to pyrethroid insecticides in the African malaria vectors Anopheles gambiae and Anopheles coluzzii. Mol. Ecol. 30, 5303\u20135317 (2021).","journal-title":"Mol. Ecol."},{"key":"8221_CR12","doi-asserted-by":"publisher","first-page":"e1009253","DOI":"10.1371\/journal.pgen.1009253","volume":"17","author":"X Grau-Bov\u00e9","year":"2021","unstructured":"Grau-Bov\u00e9, X. et al. Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus. PLoS Genet. 17, e1009253 (2021).","journal-title":"PLoS Genet."},{"key":"8221_CR13","doi-asserted-by":"publisher","first-page":"31583","DOI":"10.1073\/pnas.2018142117","volume":"117","author":"ST Small","year":"2020","unstructured":"Small, S. T. et al. Radiation with reticulation marks the origin of a major malaria vector. Proc. Natl. Acad. Sci. USA 117, 31583\u201331590 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8221_CR14","doi-asserted-by":"publisher","first-page":"1258522","DOI":"10.1126\/science.1258522","volume":"347","author":"DE Neafsey","year":"2015","unstructured":"Neafsey, D. E. et al. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes. Science 347, 1258522 (2015).","journal-title":"Science"},{"key":"8221_CR15","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1146\/annurev.ento.45.1.371","volume":"45","author":"J Hemingway","year":"2000","unstructured":"Hemingway, J. & Ranson, H. Insecticide resistance in insect vectors of human disease. Annu. Rev. Entomol. 45, 371\u2013391 (2000).","journal-title":"Annu. Rev. Entomol."},{"key":"8221_CR16","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1127\/entomologia\/2023\/1880","volume":"43","author":"VA Ingham","year":"2023","unstructured":"Ingham, V. A., Grigoraki, L. & Ranson, H. Pyrethroid resistance mechanisms in the major malaria vector species complex. Entomol. Gen. 43, 515\u2013526 (2023).","journal-title":"Entomol. Gen."},{"key":"8221_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-70713-y","volume":"14","author":"RAE Logan","year":"2024","unstructured":"Logan, R. A. E., M\u00e4urer, J. B., Wapler, C. & Ingham, V. A. Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are associated with insecticide resistance in the major malaria vectors Anopheles gambiae s.l. and Anopheles funestus. Sci. Rep. 14, 19821 (2024).","journal-title":"Sci. Rep."},{"key":"8221_CR18","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1111\/mec.16497","volume":"31","author":"J Hearn","year":"2022","unstructured":"Hearn, J. et al. Multi-omics analysis identifies a CYP9K1 haplotype conferring pyrethroid resistance in the malaria vector Anopheles funestus in East Africa. Mol. Ecol. 31, 3642\u20133657 (2022).","journal-title":"Mol. Ecol."},{"key":"8221_CR19","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/hdy.2012.53","volume":"109","author":"H Irving","year":"2012","unstructured":"Irving, H., Riveron, J. M., Ibrahim, S., Lobo, N. F. & Wondji, C. S. Positional cloning of rp2 QTL associates the P450 genes CYP6Z1, CYP6Z3 and CYP6M7 with pyrethroid resistance in the malaria vector Anopheles funestus. Heredity 109, 383\u2013392 (2012).","journal-title":"Heredity"},{"key":"8221_CR20","doi-asserted-by":"publisher","first-page":"3436","DOI":"10.1111\/mec.13673","volume":"25","author":"SS Ibrahim","year":"2016","unstructured":"Ibrahim, S. S., Ndula, M., Riveron, J. M., Irving, H. & Wondji, C. S. The P450 CYP 6Z1 confers carbamate\/pyrethroid cross-resistance in a major African malaria vector beside a novel carbamate-insensitive N485I acetylcholinesterase-1 mutation. Mol. Ecol. 25, 3436\u20133452 (2016).","journal-title":"Mol. Ecol."},{"key":"8221_CR21","doi-asserted-by":"publisher","first-page":"4619","DOI":"10.1073\/pnas.1719663115","volume":"115","author":"J Vontas","year":"2018","unstructured":"Vontas, J. et al. Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities. Proc. Natl. Acad. Sci. USA 115, 4619\u20134624 (2018).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8221_CR22","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.pestbp.2019.06.007","volume":"161","author":"C Yunta","year":"2019","unstructured":"Yunta, C. et al. Cross-resistance profiles of malaria mosquito P450s associated with pyrethroid resistance against WHO insecticides. Pestic. Biochem. Physiol. 161, 61\u201367 (2019).","journal-title":"Pestic. Biochem. Physiol."},{"key":"8221_CR23","doi-asserted-by":"publisher","first-page":"4307","DOI":"10.1111\/mec.16591","volume":"31","author":"H Njoroge","year":"2022","unstructured":"Njoroge, H. et al. Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance in Anopheles gambiae provides a real-time molecular diagnostic for antimalarial intervention deployment. Mol. Ecol. 31, 4307\u20134318 (2022).","journal-title":"Mol. Ecol."},{"key":"8221_CR24","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ibmb.2015.10.015","volume":"68","author":"SS Ibrahim","year":"2016","unstructured":"Ibrahim, S. S., Riveron, J. M., Stott, R., Irving, H. & Wondji, C. S. The cytochrome P450 CYP6P4 is responsible for the high pyrethroid resistance in knockdown resistance-free Anopheles arabiensis. Insect Biochem. Mol. Biol. 68, 23\u201332 (2016).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"8221_CR25","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.cois.2018.03.001","volume":"27","author":"V Balabanidou","year":"2018","unstructured":"Balabanidou, V., Grigoraki, L. & Vontas, J. Insect cuticle: a critical determinant of insecticide resistance. Curr. Opin. Insect Sci. 27, 68\u201374 (2018).","journal-title":"Curr. Opin. Insect Sci."},{"key":"8221_CR26","doi-asserted-by":"publisher","first-page":"9268","DOI":"10.1073\/pnas.1608295113","volume":"113","author":"V Balabanidou","year":"2016","unstructured":"Balabanidou, V. et al. Cytochrome P450 associated with insecticide resistance catalyzes cuticular hydrocarbon production in Anopheles gambiae. Proc. Natl. Acad. Sci. USA 113, 9268\u20139273 (2016).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8221_CR27","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/1756-3305-3-67","volume":"3","author":"OR Wood","year":"2010","unstructured":"Wood, O. R., Hanrahan, S., Coetzee, M., Koekemoer, L. L. & Brooke, B. D. Cuticle thickening associated with pyrethroid resistance in the major malaria vector Anopheles funestus. Parasites Vectors 3, 67 (2010).","journal-title":"Parasites Vectors"},{"key":"8221_CR28","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1046\/j.1365-2583.1998.72062.x","volume":"7","author":"D Martinez-Torres","year":"1998","unstructured":"Martinez-Torres, D. et al. Molecular characterization of pyrethroid knockdown resistance (kdr) in the major malaria vector Anopheles gambiae s.s. Insect Mol. Biol. 7, 179\u2013184 (1998).","journal-title":"Insect Mol. Biol."},{"key":"8221_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1365-2583.2004.00452.x","volume":"13","author":"M Weill","year":"2004","unstructured":"Weill, M. et al. The unique mutation in ace-1 giving high insecticide resistance is easily detectable in mosquito vectors. Insect Mol. Biol. 13, 1\u20137 (2004).","journal-title":"Insect Mol. Biol."},{"key":"8221_CR30","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s41586-019-1864-1","volume":"577","author":"VA Ingham","year":"2019","unstructured":"Ingham, V. A. et al. A sensory appendage protein protects malaria vectors from pyrethroids. Nature 577, 376\u2013380 (2019).","journal-title":"Nature"},{"key":"8221_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07615-x","volume":"9","author":"VA Ingham","year":"2018","unstructured":"Ingham, V. A., Wagstaff, S. & Ranson, H. Transcriptomic meta-signatures identified in Anopheles gambiae populations reveal previously undetected insecticide resistance mechanisms. Nat. Commun. 9, 5282 (2018).","journal-title":"Nat. Commun."},{"key":"8221_CR32","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/nature24995","volume":"552","author":"The Anopheles gambiae 1000 Genomes Consortium","year":"2017","unstructured":"The Anopheles gambiae 1000 Genomes Consortium. Genetic diversity of the African malaria vector Anopheles gambiae. Nature 552, 96 (2017).","journal-title":"Nature"},{"key":"8221_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-4086-7","volume":"18","author":"VA Ingham","year":"2017","unstructured":"Ingham, V. A., Pignatelli, P., Moore, J. D., Wagstaff, S. & Ranson, H. The transcription factor Maf-S regulates metabolic resistance to insecticides in the malaria vector Anopheles gambiae. BMC Genom. 18, 669 (2017).","journal-title":"BMC Genom."},{"key":"8221_CR34","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/insects13030247","volume":"13","author":"J Williams","year":"2022","unstructured":"Williams, J. et al. Sympatric populations of the Anopheles gambiae complex in Southwest Burkina Faso evolve multiple diverse resistance mechanisms in response to intense selection pressure with pyrethroids. Insects 13, 247 (2022).","journal-title":"Insects"},{"key":"8221_CR35","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1002\/ps.5374","volume":"75","author":"EA Simma","year":"2019","unstructured":"Simma, E. A. et al. Genome-wide gene expression profiling reveals that cuticle alterations and P450 detoxification are associated with deltamethrin and DDT resistance in Anopheles arabiensis populations from Ethiopia. Pest Manag. Sci. 75, 1808\u20131818 (2019).","journal-title":"Pest Manag. Sci."},{"key":"8221_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2021.103655","volume":"139","author":"LA Messenger","year":"2021","unstructured":"Messenger, L. A. et al. A whole transcriptomic approach provides novel insights into the molecular basis of organophosphate and pyrethroid resistance in Anopheles arabiensis from Ethiopia. Insect Biochem. Mol. Biol. 139, 103655 (2021).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"8221_CR37","doi-asserted-by":"publisher","first-page":"e1009970","DOI":"10.1371\/journal.pgen.1009970","volume":"17","author":"VA Ingham","year":"2021","unstructured":"Ingham, V. A. et al. Integration of whole genome sequencing and transcriptomics reveals a complex picture of the reestablishment of insecticide resistance in the major malaria vector Anopheles coluzzii. PLOS Genet. 17, e1009970 (2021).","journal-title":"PLOS Genet."},{"key":"8221_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-023-01610-5","volume":"21","author":"SS Ibrahim","year":"2023","unstructured":"Ibrahim, S. S. et al. Molecular drivers of insecticide resistance in the Sahelo-Sudanian populations of a major malaria vector Anopheles coluzzii. BMC Biol. 21, 125 (2023).","journal-title":"BMC Biol."},{"key":"8221_CR39","doi-asserted-by":"publisher","first-page":"e1009963","DOI":"10.1371\/journal.pgen.1009963","volume":"18","author":"NC Wipf","year":"2022","unstructured":"Wipf, N. C. et al. Multi-insecticide resistant malaria vectors in the field remain susceptible to malathion, despite the presence of Ace1 point mutations. PLOS Genet. 18, e1009963 (2022).","journal-title":"PLOS Genet."},{"key":"8221_CR40","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3390\/genes12040561","volume":"12","author":"MFM Kouamo","year":"2021","unstructured":"Kouamo, M. F. M. et al. Genome-wide transcriptional analysis and functional validation linked a cluster of epsilon glutathione S-transferases with insecticide resistance in the major malaria vector Anopheles funestus across Africa. Genes 12, 561 (2021).","journal-title":"Genes"},{"key":"8221_CR41","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1111\/1755-0998.13759","volume":"23","author":"SC Nagi","year":"2023","unstructured":"Nagi, S. C., Oruni, A., Weetman, D. & Donnelly, M. J. RNA-Seq-Pop: exploiting the sequence in RNA sequencing\u2014a Snakemake workflow reveals patterns of insecticide resistance in the malaria vector Anopheles gambiae. Mol. Ecol. Resour. 23, 946\u2013961 (2023).","journal-title":"Mol. Ecol. Resour."},{"key":"8221_CR42","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.csbj.2021.12.015","volume":"20","author":"T-H Yang","year":"2022","unstructured":"Yang, T.-H., Yang, Y.-C. & Tu, K.-C. regCNN: identifying Drosophila genome-wide cis-regulatory modules via integrating the local patterns in epigenetic marks and transcription factor binding motifs. Comput. Struct. Biotechnol. J. 20, 296\u2013308 (2022).","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"8221_CR43","doi-asserted-by":"publisher","first-page":"e1001388","DOI":"10.1371\/journal.pbio.1001388","volume":"10","author":"EM Leffler","year":"2012","unstructured":"Leffler, E. M. et al. Revisiting an old riddle: What determines genetic diversity levels within species?. PLOS Biol. 10, e1001388 (2012).","journal-title":"PLOS Biol."},{"key":"8221_CR44","doi-asserted-by":"publisher","first-page":"e1005004","DOI":"10.1371\/journal.pgen.1005004","volume":"11","author":"NR Garud","year":"2015","unstructured":"Garud, N. R., Messer, P. W., Buzbas, E. O. & Petrov, D. A. Recent selective sweeps in North American Drosophila melanogaster show signatures of soft sweeps. PLOS Genet. 11, e1005004 (2015).","journal-title":"PLOS Genet."},{"key":"8221_CR45","doi-asserted-by":"publisher","first-page":"e1000286","DOI":"10.1371\/journal.pgen.1000286","volume":"4","author":"P M\u00fcller","year":"2008","unstructured":"M\u00fcller, P. et al. Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids. PLoS Genet. 4, e1000286 (2008).","journal-title":"PLoS Genet."},{"key":"8221_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12864-018-4605-1","volume":"19","author":"AT Isaacs","year":"2018","unstructured":"Isaacs, A. T., Mawejje, H. D., Tomlinson, S., Rigden, D. J. & Donnelly, M. J. Genome-wide transcriptional analyses in Anopheles mosquitoes reveal an unexpected association between salivary gland gene expression and insecticide resistance. BMC Genom. 19, 1\u201312 (2018).","journal-title":"BMC Genom."},{"key":"8221_CR47","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.bbrc.2005.09.043","volume":"337","author":"T Namiki","year":"2005","unstructured":"Namiki, T. et al. Cytochrome P450 CYP307A1\/Spook: a regulator for ecdysone synthesis in insects. Biochem. Biophys. Res. Commun. 337, 367\u2013374 (2005).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"8221_CR48","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1042\/bj20030169","volume":"373","author":"F Ortelli","year":"2003","unstructured":"Ortelli, F., Rossiter, L. C., Vontas, J., Ranson, H. & Hemingway, J. Heterologous expression of four glutathione transferase genes genetically linked to a major insecticide-resistance locus from the malaria vector Anopheles gambiae. Biochem. J. 373, 957\u2013963 (2003).","journal-title":"Biochem. J."},{"key":"8221_CR49","doi-asserted-by":"publisher","unstructured":"Ingham, V. A., Elg, S., Nagi, S. C. & Dondelinger, F. Capturing the transcription factor interactome in response to sub-lethal insecticide exposure. Curr. Res. Insect Sci. 100018. https:\/\/doi.org\/10.1016\/j.cris.2021.100018(2021).","DOI":"10.1016\/j.cris.2021.100018"},{"key":"8221_CR50","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/oxfordjournals.molbev.a026239","volume":"17","author":"L Duret","year":"2000","unstructured":"Duret, L. & Mouchiroud, D. Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Mol. Biol. Evol. 17, 68\u2013070 (2000).","journal-title":"Mol. Biol. Evol."},{"key":"8221_CR51","doi-asserted-by":"crossref","unstructured":"Leon, M. et al. Association of a rapidly selected 43.kb transposon-containing structural variation with a P450-based resistance to pyrethroids in the African malaria vector Anopheles funestus. PLoS Genetics 20, e1011344 (2024).","DOI":"10.1371\/journal.pgen.1011344"},{"key":"8221_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13071-021-04609-5","volume":"14","author":"CL Moyes","year":"2021","unstructured":"Moyes, C. L. et al. Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations. Parasites Vectors 14, 1\u201313 (2021).","journal-title":"Parasites Vectors"},{"key":"8221_CR53","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1101\/gr.245795.118","volume":"29","author":"ER Lucas","year":"2019","unstructured":"Lucas, E. R. et al. Whole-genome sequencing reveals high complexity of copy number variation at insecticide resistance loci in malaria mosquitoes. Genome Res. 29, 1250\u20131261 (2019).","journal-title":"Genome Res."},{"key":"8221_CR54","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.gene.2007.06.013","volume":"400","author":"E Lavara-Culebras","year":"2007","unstructured":"Lavara-Culebras, E. & Paricio, N. Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits. Gene 400, 158\u2013165 (2007).","journal-title":"Gene"},{"key":"8221_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31360-2","volume":"8","author":"CJ Champion","year":"2018","unstructured":"Champion, C. J. & Xu, J. Redox state affects fecundity and insecticide susceptibility in Anopheles gambiae. Sci. Rep. 8, 13054 (2018).","journal-title":"Sci. Rep."},{"key":"8221_CR56","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1017\/S0007485314000091","volume":"104","author":"D Otali","year":"2014","unstructured":"Otali, D. et al. Increased production of mitochondrial reactive oxygen species and reduced adult life span in an insecticide-resistant strain of Anopheles gambiae. Bull. Entomol. Res. 104, 323\u2013333 (2014).","journal-title":"Bull. Entomol. Res."},{"key":"8221_CR57","doi-asserted-by":"publisher","first-page":"e1011448","DOI":"10.1371\/journal.ppat.1011448","volume":"19","author":"KL Adams","year":"2023","unstructured":"Adams, K. L. et al. Selection for insecticide resistance can promote Plasmodium falciparum infection in Anopheles. PLOS Pathog. 19, e1011448 (2023).","journal-title":"PLOS Pathog."},{"key":"8221_CR58","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1038\/s42003-021-02434-1","volume":"4","author":"KL Adams","year":"2021","unstructured":"Adams, K. L. et al. Cuticular hydrocarbons are associated with mating success and insecticide resistance in malaria vectors. Commun. Biol. 4, 911 (2021).","journal-title":"Commun. Biol."},{"key":"8221_CR59","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-023-04671-7","volume":"22","author":"NJ Govella","year":"2023","unstructured":"Govella, N. J., Johnson, P. C. D., Killeen, G. F. & Ferguson, H. M. Heritability of biting time behaviours in the major African malaria vector Anopheles arabiensis. Malar. J. 22, 238 (2023).","journal-title":"Malar. J."},{"key":"8221_CR60","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1016\/j.ibmb.2012.07.005","volume":"42","author":"M Ruiz","year":"2012","unstructured":"Ruiz, M., Wicker-Thomas, C., Sanchez, D. & Ganfornina, M. D. Grasshopper Lazarillo, a GPI-anchored Lipocalin, increases Drosophila longevity and stress resistance, and functionally replaces its secreted homolog NLaz. Insect Biochem. Mol. Biol. 42, 776\u2013789 (2012).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"8221_CR61","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1093\/jme\/tjv059","volume":"52","author":"Y Lv","year":"2015","unstructured":"Lv, Y. et al. Venom allergen 5 is associated with deltamethrin resistance in Culex pipiens pallens (Diptera: Culicidae). J. Med. Entomol. 52, 672\u2013682 (2015).","journal-title":"J. Med. Entomol."},{"key":"8221_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-3579-8","volume":"18","author":"B Arc\u00e0","year":"2017","unstructured":"Arc\u00e0, B., Lombardo, F., Struchiner, C. J. & Ribeiro, J. M. C. Anopheline salivary protein genes and gene families: an evolutionary overview after the whole genome sequence of sixteen Anopheles species. BMC Genom. 18, 153 (2017).","journal-title":"BMC Genom."},{"key":"8221_CR63","doi-asserted-by":"publisher","DOI":"10.1002\/arch.21869","volume":"109","author":"L Gao","year":"2022","unstructured":"Gao, L., Qiao, H., Wei, P., Moussian, B. & Wang, Y. Xenobiotic responses in insects. Arch. Insect Biochem. Physiol. 109, e21869 (2022).","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"8221_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-34","volume":"8","author":"CS Wondji","year":"2007","unstructured":"Wondji, C. S. et al. Mapping a Quantitative Trait Locus (QTL) conferring pyrethroid resistance in the African malaria vector Anopheles funestus. BMC Genom. 8, 34 (2007).","journal-title":"BMC Genom."},{"key":"8221_CR65","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12686-5","volume":"10","author":"LMJ Mugenzi","year":"2019","unstructured":"Mugenzi, L. M. J. et al. Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus. Nat. Commun. 10, 4652 (2019).","journal-title":"Nat. Commun."},{"key":"8221_CR66","doi-asserted-by":"publisher","DOI":"10.1186\/s13630-015-0018-9","volume":"4","author":"K Styczynska-Soczka","year":"2015","unstructured":"Styczynska-Soczka, K. & Jarman, A. P. The Drosophila homologue of Rootletin is required for mechanosensory function and ciliary rootlet formation in chordotonal sensory neurons. Cilia 4, 9 (2015).","journal-title":"Cilia"},{"key":"8221_CR67","doi-asserted-by":"publisher","first-page":"e0211497","DOI":"10.1371\/journal.pone.0211497","volume":"14","author":"CL Campbell","year":"2019","unstructured":"Campbell, C. L. et al. Vgsc-interacting proteins are genetically associated with pyrethroid resistance in Aedes aegypti. PLoS ONE 14, e0211497 (2019).","journal-title":"PLoS ONE"},{"key":"8221_CR68","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022583118","volume":"118","author":"S Mukherjee","year":"2021","unstructured":"Mukherjee, S., Paricio, N. & Sokol, N. S. A stress-responsive miRNA regulates BMP signaling to maintain tissue homeostasis. Proc. Natl. Acad. Sci. USA 118, e2022583118 (2021).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8221_CR69","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E21-08-0418","volume":"33","author":"A Singh","year":"2022","unstructured":"Singh, A. et al. The transcriptional response to oxidative stress is independent of stress-granule formation. Mol. Biol. Cell 33, ar25 (2022).","journal-title":"Mol. Biol. Cell"},{"key":"8221_CR70","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1126\/science.1107573","volume":"308","author":"KA Mace","year":"2005","unstructured":"Mace, K. A., Pearson, J. C. & McGinnis, W. An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head. Science 308, 381\u2013385 (2005).","journal-title":"Science"},{"key":"8221_CR71","doi-asserted-by":"publisher","first-page":"9143","DOI":"10.1523\/JNEUROSCI.22-21-09143.2002","volume":"22","author":"PO Joanne","year":"2002","unstructured":"Joanne, P. O., Scott, H. & Chris, Q. D. DrosophilaHB9 is expressed in a subset of motoneurons and interneurons, where it regulates gene expression and axon pathfinding.  J. Neurosci. 22, 9143 (2002).","journal-title":"J. Neurosci."},{"key":"8221_CR72","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0925-4773(00)00431-7","volume":"97","author":"DNT Nguyen","year":"2000","unstructured":"Nguyen, D. N. T., Rohrbaugh, M. & Lai, Z.-C. The Drosophila homolog of Onecut homeodomain proteins is a neural-specific transcriptional activator with a potential role in regulating neural differentiation. Mech. Dev. 97, 57\u201372 (2000).","journal-title":"Mech. Dev."},{"key":"8221_CR73","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.bbrc.2012.11.084","volume":"430","author":"T Matsuda","year":"2013","unstructured":"Matsuda, T., Kanki, T., Tanimura, T., Kang, D. & Matsuura, E. T. Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster. Biochem. Biophys. Res. Commun. 430, 717\u2013721 (2013).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"8221_CR74","doi-asserted-by":"publisher","unstructured":"Emiliano, T. et al. Gene expression is the main driver of purifying selection in large penguin populations. bioRxiv, 2023.2008.2008.552445. https:\/\/doi.org\/10.1101\/2023.08.08.552445 (2023).","DOI":"10.1101\/2023.08.08.552445"},{"key":"8221_CR75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 1\u201321 (2014).","journal-title":"Genome Biol."},{"key":"8221_CR76","doi-asserted-by":"publisher","first-page":"D707","DOI":"10.1093\/nar\/gku1117","volume":"43","author":"GI Giraldo-Calder\u00f3n","year":"2015","unstructured":"Giraldo-Calder\u00f3n, G. I. et al. VectorBase: an updated bioinformatics resource for invertebrate vectors and other organisms related with human diseases. Nucleic Acids Res. 43, D707\u2013D713 (2015).","journal-title":"Nucleic Acids Res."},{"key":"8221_CR77","doi-asserted-by":"publisher","first-page":"2900","DOI":"10.1093\/molbev\/msaa128","volume":"37","author":"X Grau-Bov\u00e9","year":"2020","unstructured":"Grau-Bov\u00e9, X. et al. Evolution of the insecticide target Rdl in African Anopheles is driven by interspecific and interkaryotypic introgression. Mol. Biol. Evol. 37, 2900\u20132917 (2020).","journal-title":"Mol. Biol. Evol."},{"key":"8221_CR78","doi-asserted-by":"publisher","unstructured":"Alistair Miles. \u2018cggh\/scikit-allel: v1.3.9\u2019. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.13467522 (2024).","DOI":"10.5281\/zenodo.13467522"},{"key":"8221_CR79","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-024-05106-7","volume":"23","author":"M Kientega","year":"2024","unstructured":"Kientega, M. et al. Whole-genome sequencing of major malaria vectors reveals the evolution of new insecticide resistance variants in a longitudinal study in Burkina Faso. Malar. J. 23, 280 (2024).","journal-title":"Malar. J."},{"key":"8221_CR80","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-024-04950-x","volume":"23","author":"L Kamau","year":"2024","unstructured":"Kamau, L. et al. The Anopheles coluzzii range extends into Kenya: detection, insecticide resistance profiles and population genetic structure in relation to conspecific populations in West and Central Africa. Malar. J. 23, 122 (2024).","journal-title":"Malar. J."},{"key":"8221_CR81","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-70885-7","volume":"14","author":"TPW Dennis","year":"2024","unstructured":"Dennis, T. P. W. et al. Cryptic population structure and insecticide resistance in Anopheles gambiae from the southern Democratic Republic of Congo. Sci. Rep. 14, 21782 (2024).","journal-title":"Sci. Rep."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08221-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08221-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08221-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T12:05:36Z","timestamp":1748001936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08221-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,23]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8221"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08221-6","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,23]]},"assertion":[{"value":"5 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"790"}}