{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:12:15Z","timestamp":1789992735809,"version":"4.0.1"},"reference-count":71,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV\u2010006003"],"award-info":[{"award-number":["INV\u2010006003"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Ecology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Metabolic resistance to pyrethroids is a menace to the continued effectiveness of malaria vector controls. Its molecular basis is complex and varies geographically across Africa. Here, we used a multi\u2010omics approach, followed\u2010up with functional validation to show that a directionally selected haplotype of a cytochrome P450,\n                    <jats:italic>CYP9K1<\/jats:italic>\n                    is a major driver of resistance in\n                    <jats:italic>Anopheles funestus<\/jats:italic>\n                    . A PoolSeq GWAS using mosquitoes alive and dead after permethrin exposure, from Malawi and Cameroon, detected candidate genomic regions, but lacked consistency across replicates. Targeted sequencing of candidate resistance genes detected several SNPs associated with known pyrethroid resistance QTLs. The most significant SNPs were in the cytochrome P450\n                    <jats:italic>CYP304B1<\/jats:italic>\n                    (Cameroon),\n                    <jats:italic>CYP315A1<\/jats:italic>\n                    (Uganda) and the ABC transporter gene ABCG4 (Malawi). However, when comparing field resistant mosquitoes to laboratory susceptible, the pyrethroid resistance locus\n                    <jats:italic>rp1<\/jats:italic>\n                    and SNPs around the ABC transporter ABCG4 were consistently significant, except for Uganda where SNPs in the P450\n                    <jats:italic>CYP9K1<\/jats:italic>\n                    was markedly significant. In vitro heterologous metabolism assays with recombinant\n                    <jats:italic>CYP9K1<\/jats:italic>\n                    revealed that it metabolises type II pyrethroid (deltamethrin; 64% depletion) but not type I (permethrin; 0%), while moderately metabolising DDT (17%).\n                    <jats:italic>CYP9K1<\/jats:italic>\n                    exhibited reduced genetic diversity in Uganda underlying an extensive selective sweep. Furthermore, a glycine to alanine (G454A) amino acid change in\n                    <jats:italic>CYP9K1<\/jats:italic>\n                    was fixed in Ugandan mosquitoes but not in other\n                    <jats:italic>An<\/jats:italic>\n                    .\n                    <jats:italic>funestus<\/jats:italic>\n                    populations. This study sheds further light on the evolution of metabolic resistance in a major malaria vector by implicating more genes and variants that can be used to design field\u2010applicable markers to better track resistance Africa\u2010wide.\n                  <\/jats:p>","DOI":"10.1111\/mec.16497","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T01:11:09Z","timestamp":1652317869000},"page":"3642-3657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Multi\u2010omics analysis identifies a\n                    <i>CYP9K1<\/i>\n                    haplotype conferring pyrethroid resistance in the malaria vector\n                    <i>Anopheles funestus<\/i>\n                    in East Africa"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3358-4949","authenticated-orcid":false,"given":"Jack","family":"Hearn","sequence":"first","affiliation":[{"name":"Vector Biology Department Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos S.","family":"Djoko Tagne","sequence":"additional","affiliation":[{"name":"LSTM Research Unit Centre for Research in Infectious Diseases (CRID)  Yaound\u00e9 Cameroon"},{"name":"Department of Biochemistry Faculty of Science University of Bamenda  Bamenda Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0744-802X","authenticated-orcid":false,"given":"Sulaiman S.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Vector Biology Department Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Tene\u2010Fossog","sequence":"additional","affiliation":[{"name":"LSTM Research Unit Centre for Research in Infectious Diseases (CRID)  Yaound\u00e9 Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6857-9608","authenticated-orcid":false,"given":"Leon M. J.","family":"Mugenzi","sequence":"additional","affiliation":[{"name":"LSTM Research Unit Centre for Research in Infectious Diseases (CRID)  Yaound\u00e9 Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Irving","sequence":"additional","affiliation":[{"name":"Vector Biology Department Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Riveron","sequence":"additional","affiliation":[{"name":"Vector Biology Department Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8927-1063","authenticated-orcid":false,"given":"Gareth D.","family":"Weedall","sequence":"additional","affiliation":[{"name":"School of Biological and Environmental Sciences Liverpool John Moores University  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-3673","authenticated-orcid":false,"given":"Charles S.","family":"Wondji","sequence":"additional","affiliation":[{"name":"Vector Biology Department Liverpool School of Tropical Medicine  Liverpool UK"},{"name":"LSTM Research Unit Centre for Research in Infectious Diseases (CRID)  Yaound\u00e9 Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102583.2008.00776.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936\u2010015\u20100675\u20106"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cois.2018.03.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1615458114"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006539"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003534"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15535"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/eva.12867"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20130577"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709249105"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014202"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074170"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2013.11.001"},{"key":"e_1_2_9_16_1","first-page":"55389","article-title":"Advances and perspectives in the study of the malaria mosquito Anopheles funestus","volume":"10","author":"Dia I.","year":"2013","journal-title":"Anopheles Mosquitoes\u2010New Insights into Malaria Vectors"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11111314"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.189225.115"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm268"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.28.445945"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giz063"},{"key":"e_1_2_9_22_1","volume-title":"A supplement to the Anophelinae of Africa south of the Sahara (Afrotropical region)","author":"Gillies M. 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