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Integration of whole genome sequencing and transcriptomics reveals a complex picture of insecticide resistance in the major malaria vector Anopheles coluzzii

VA Ingham, JA Tennessen, ER Lucas, S Elg, H Carrington-Yates, J Carson, WM Guelbeogo, N Sagnon, View ORCID ProfileG Hughes, E Heinz, DE Neafsey, H Ranson
doi: https://doi.org/10.1101/2021.08.21.457189
VA Ingham
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
2Parasitology Unit, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
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  • For correspondence: Victoria.ingham@uni-heidelberg.de Hilary.ranson@lstmed.ac.uk
JA Tennessen
3The Broad Institute, 415 Main St, Cambridge, MA 02142, USA
4Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
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ER Lucas
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
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S Elg
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
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H Carrington-Yates
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
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J Carson
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
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WM Guelbeogo
5The Centre National de Recherche et de Formation sur le Paludisme, 2208 Ougadougou, Burkina Faso
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N Sagnon
5The Centre National de Recherche et de Formation sur le Paludisme, 2208 Ougadougou, Burkina Faso
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G Hughes
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
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  • ORCID record for G Hughes
E Heinz
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
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DE Neafsey
3The Broad Institute, 415 Main St, Cambridge, MA 02142, USA
4Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
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H Ranson
1Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, L35QA, UK
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  • For correspondence: Victoria.ingham@uni-heidelberg.de Hilary.ranson@lstmed.ac.uk
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Abstract

Insecticide resistance is a major threat to gains in malaria control, which have been stalling and potentially reversing since 2015. Studies into the causal mechanisms of insecticide resistance are painting an increasingly complicated picture, underlining the need to design and implement targeted studies on this phenotype. In this study, we compare three populations of the major malaria vector An. coluzzii: a susceptible and two resistant colonies with the same genetic background. The original colonised resistant population rapidly lost resistance over a 6-month period, a subset of this population was reselected with pyrethroids a third population of this colony that did not lose resistance was also available. The original resistant, susceptible and re-selected colonies were subject to RNAseq and whole genome sequencing, which identified a number of changes across the transcriptome and genome linked with resistance. Firstly, an increase in the expression of genes within the oxidative phosphorylation pathway were seen in both resistant populations compared to the susceptible control; this translated phenotypically through an increased respiratory rate, indicating that elevated metabolism is linked directly with resistance. Genome sequencing highlighted several blocks clearly associated with resistance, including the 2Rb inversion. Finally, changes in the microbiome profile were seen, indicating that the microbial composition may play a role in the resistance phenotype. Taken together, this study reveals a highly complicated phenotype in which multiple transcriptomic, genomic and microbiome changes combine to result in insecticide resistance.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 21, 2021.
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Integration of whole genome sequencing and transcriptomics reveals a complex picture of insecticide resistance in the major malaria vector Anopheles coluzzii
VA Ingham, JA Tennessen, ER Lucas, S Elg, H Carrington-Yates, J Carson, WM Guelbeogo, N Sagnon, G Hughes, E Heinz, DE Neafsey, H Ranson
bioRxiv 2021.08.21.457189; doi: https://doi.org/10.1101/2021.08.21.457189
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Integration of whole genome sequencing and transcriptomics reveals a complex picture of insecticide resistance in the major malaria vector Anopheles coluzzii
VA Ingham, JA Tennessen, ER Lucas, S Elg, H Carrington-Yates, J Carson, WM Guelbeogo, N Sagnon, G Hughes, E Heinz, DE Neafsey, H Ranson
bioRxiv 2021.08.21.457189; doi: https://doi.org/10.1101/2021.08.21.457189

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