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.