Transposable elements as genetic drivers of over-expression of detoxification genes in malaria vectors as the presence of 4.3kb increased expression of nearby P450s
Transposable elements are over-represented near P450s clusters in insects (Chen & Li, 2007). They can affect the expression of the gene(s) by bringing regulatory elements that can either repress or enhance the expression of nearby genes (Guio et al., 2014). Genetic crosses were used to compare the expression of three genes located near this 4.3kb SV between the 3 genotypes SV+/SV+, SV+/SV- and SV-/SV- as previously done for the 6.5kb SV (Mugenzi et al., 2020). Increased expression of 2 genes (CYP6P9a and CYP6P9b ) was found only in the homozygote SV+/SV+. This higher expression of nearby P450s in the homozygote SV+/SV+ suggests that the transposons contained in this 4.3kb region may act as enhancers. Increased expression was also seen in wildtype RNASeq for Ugandan versus susceptible FANG mosquitoes sampled in 2014 (Weedall et al., 2019) but was less clear cut than the crossing data due to complex expression of CYP6P9b in particular across Africa. In D. melanogaster, the up-regulation of CYP6G1conferring resistance to a variety of insecticide classes (Daborn et al., 2001) correlates with the presence of an Accord retrotransposon in the 5’ UTR region and this retro-transposable element contains regulatory sequences capable of increasing the expression ofCYP6G1 in detoxification organs (Chung et al., 2007). The 4.3kb SV identified here could regulate the expression of CYP6P9a/b by providing regulatory elements. However, further studies are needed to functionally validate this hypothesis using luciferase promoter assay or promoter assays in transgenic mosquitoes.