Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii
Abstract Background The emergence of insecticide resistance is a major threat to malaria control programmes in Africa, with many different factors contributing to insecticide resistance in its vectors, Anopheles mosquitoes. CYP6M2 has previously been recognized as an important candidate in cytochrom...
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ftdoajarticles:oai:doaj.org/article:49f2f928b38841c99dc5f67a3a9680a6 2023-05-15T15:15:32+02:00 Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii Martin G. Wagah Petra Korlević Christopher Clarkson Alistair Miles The Anopheles gambiae 1000 Genomes Consortium Mara K. N. Lawniczak Alex Makunin 2021-05-01T00:00:00Z https://doi.org/10.1186/s12936-021-03757-4 https://doaj.org/article/49f2f928b38841c99dc5f67a3a9680a6 EN eng BMC https://doi.org/10.1186/s12936-021-03757-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03757-4 1475-2875 https://doaj.org/article/49f2f928b38841c99dc5f67a3a9680a6 Malaria Journal, Vol 20, Iss 1, Pp 1-13 (2021) Mosquito Cyp6m2 Metabolic resistance Allelic variants Selection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-021-03757-4 2022-12-31T07:51:47Z Abstract Background The emergence of insecticide resistance is a major threat to malaria control programmes in Africa, with many different factors contributing to insecticide resistance in its vectors, Anopheles mosquitoes. CYP6M2 has previously been recognized as an important candidate in cytochrome P450-mediated detoxification in Anopheles. As it has been implicated in resistance against pyrethroids, organochlorines and carbamates, its broad metabolic activity makes it a potential agent in insecticide cross-resistance. Currently, allelic variation within the Cyp6m2 gene remains unknown. Methods Here, Illumina whole-genome sequence data from Phase 2 of the Anopheles gambiae 1000 Genomes Project (Ag1000G) was used to examine genetic variation in the Cyp6m2 gene across 16 populations in 13 countries comprising Anopheles gambiae and Anopheles coluzzii mosquitoes. To identify whether these alleles show evidence of selection either through potentially modified enzymatic function or by being linked to variants that change the transcriptional profile of the gene, hierarchical clustering of haplotypes, linkage disequilibrium, median joining networks and extended haplotype homozygosity analyses were performed. Results Fifteen missense biallelic substitutions at high frequency (defined as > 5% frequency in one or more populations) are found, which fall into five distinct haplotype groups that carry the main high frequency variants: A13T, D65A, E328Q, Y347F, I359V and A468S. Despite consistent reports of Cyp6m2 upregulation and metabolic activity in insecticide resistant Anophelines, no evidence of directional selection is found occurring on these variants or on the haplotype clusters in which they are found. Conclusion These results imply that emerging resistance associated with Cyp6m2 is potentially driven by distant regulatory loci such as transcriptional factors rather than by its missense variants, or that other genes are playing a more significant role in conferring metabolic resistance. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
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English |
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Mosquito Cyp6m2 Metabolic resistance Allelic variants Selection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Mosquito Cyp6m2 Metabolic resistance Allelic variants Selection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Martin G. Wagah Petra Korlević Christopher Clarkson Alistair Miles The Anopheles gambiae 1000 Genomes Consortium Mara K. N. Lawniczak Alex Makunin Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii |
topic_facet |
Mosquito Cyp6m2 Metabolic resistance Allelic variants Selection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The emergence of insecticide resistance is a major threat to malaria control programmes in Africa, with many different factors contributing to insecticide resistance in its vectors, Anopheles mosquitoes. CYP6M2 has previously been recognized as an important candidate in cytochrome P450-mediated detoxification in Anopheles. As it has been implicated in resistance against pyrethroids, organochlorines and carbamates, its broad metabolic activity makes it a potential agent in insecticide cross-resistance. Currently, allelic variation within the Cyp6m2 gene remains unknown. Methods Here, Illumina whole-genome sequence data from Phase 2 of the Anopheles gambiae 1000 Genomes Project (Ag1000G) was used to examine genetic variation in the Cyp6m2 gene across 16 populations in 13 countries comprising Anopheles gambiae and Anopheles coluzzii mosquitoes. To identify whether these alleles show evidence of selection either through potentially modified enzymatic function or by being linked to variants that change the transcriptional profile of the gene, hierarchical clustering of haplotypes, linkage disequilibrium, median joining networks and extended haplotype homozygosity analyses were performed. Results Fifteen missense biallelic substitutions at high frequency (defined as > 5% frequency in one or more populations) are found, which fall into five distinct haplotype groups that carry the main high frequency variants: A13T, D65A, E328Q, Y347F, I359V and A468S. Despite consistent reports of Cyp6m2 upregulation and metabolic activity in insecticide resistant Anophelines, no evidence of directional selection is found occurring on these variants or on the haplotype clusters in which they are found. Conclusion These results imply that emerging resistance associated with Cyp6m2 is potentially driven by distant regulatory loci such as transcriptional factors rather than by its missense variants, or that other genes are playing a more significant role in conferring metabolic resistance. |
format |
Article in Journal/Newspaper |
author |
Martin G. Wagah Petra Korlević Christopher Clarkson Alistair Miles The Anopheles gambiae 1000 Genomes Consortium Mara K. N. Lawniczak Alex Makunin |
author_facet |
Martin G. Wagah Petra Korlević Christopher Clarkson Alistair Miles The Anopheles gambiae 1000 Genomes Consortium Mara K. N. Lawniczak Alex Makunin |
author_sort |
Martin G. Wagah |
title |
Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii |
title_short |
Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii |
title_full |
Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii |
title_fullStr |
Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii |
title_full_unstemmed |
Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii |
title_sort |
genetic variation at the cyp6m2 putative insecticide resistance locus in anopheles gambiae and anopheles coluzzii |
publisher |
BMC |
publishDate |
2021 |
url |
https://doi.org/10.1186/s12936-021-03757-4 https://doaj.org/article/49f2f928b38841c99dc5f67a3a9680a6 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-13 (2021) |
op_relation |
https://doi.org/10.1186/s12936-021-03757-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03757-4 1475-2875 https://doaj.org/article/49f2f928b38841c99dc5f67a3a9680a6 |
op_doi |
https://doi.org/10.1186/s12936-021-03757-4 |
container_title |
Malaria Journal |
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20 |
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1 |
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1766345909450309632 |