TY - JOUR
T1 - Integration of whole genome sequencing and transcriptomics reveals a complex picture of the reestablishment of insecticide resistance in the major malaria vector Anopheles coluzzii
AU - Ingham, Victoria A.
AU - Tennessen, Jacob A.
AU - Lucas, Eric R.
AU - Elg, Sara
AU - Yates, Henrietta Carrington
AU - Carson, Jessica
AU - Guelbeogo, Wamdaogo Moussa
AU - Sagnon, N'Fale
AU - Hughes, Grant L.
AU - Heinz, Eva
AU - Neafsey, Daniel E.
AU - Ranson, Hilary
PY - 2021/12/23
Y1 - 2021/12/23
N2 - 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, and 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.
AB - 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, and 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.
KW - Insecticide resistance
KW - malaria
KW - Genome sequencing
KW - microbiome
UR - http://www.scopus.com/inward/record.url?scp=85122333085&partnerID=8YFLogxK
UR - https://github.com/VictoriaIngham/Banfora_Paper.
U2 - 10.1371/journal.pgen.1009970
DO - 10.1371/journal.pgen.1009970
M3 - Article
C2 - 34941884
AN - SCOPUS:85122333085
SN - 1553-7390
VL - 17
JO - PLOS Genetics
JF - PLOS Genetics
IS - 12
M1 - e1009970
ER -