A Transposable Element Insertion Confers Xenobiotic Resistance in Drosophila

Abstract

The increase in availability of whole genome sequences makes it possible to search for evidence of adaptation at an unprecedented scale. Despite recent progress, our understanding of the adaptive process is still very limited due to the difficulties in linking adaptive mutations to their phenotypic effects. In this study, we integrated different levels of biological information to pinpoint the ecologically relevant fitness effects and the underlying molecular and biochemical mechanisms of a putatively adaptive TE insertion in Drosophila melanogaster: the pogo transposon FBti0019627. We showed that other than being incorporated into Kmn1 transcript, FBti0019627 insertion also affects the polyadenylation signal choice of CG11699 gene. Consequently, only the short 3′UTR transcript of CG11699 gene is produced and the expression level of this gene is higher in flies with the insertion. Our results indicated that increased CG11699 expression leads to xenobiotic stress resistance through increased ALDH-III activity: flies with FBti0019627 insertion showed increased survival rate in response to benzaldehyde, a natural xenobiotic, and to carbofuran, a synthetic insecticide. Although differences in survival rate between flies with and without the insertion were not always significant, when they were, they were consistent with FBti0019627 mediating resistance to xenobiotics. Taken together, our results provide a plausible explanation for the increase in frequency of FBti0019627 in natural populations of D. melanogaster and add to the limited number of examples in which a natural genetic mutation has been linked to its ecologically relevant phenotype. Furthermore, the widespread distribution of TEs across the tree of life and conservation of stress response pathways across organisms make our results relevant not only for Drosophila, but for other organisms as well.

Regulatory activities of transposable elements: from conflicts to benefits

“…An interesting example is the adaptive insertion of a POGON1 DNA transposon within the 3′ UTR of the gene CG11699 in D. melanogaster 52 . The insertion disrupts the ‘normal’ (ancestral) polyadenylation signal of the gene resulting in a shorter 3′ UTR, elevated mRNA levels, and increased resistance to xenobiotic stress 52 . TEs may also exert a broad influence on genome regulation as a result of their targeting by host silencing pathways 33 (Fig.…”

“…Some of the adaptive TE insertions that recently swept in the Drosophila melanogaster population may represent examples of new cis -regulatory sequences gained by transposition 179 . It could also be that some TEs have immediate cis -regulatory effects that are independent of their own sequences, simply through their disruptive 52 or epigenetic activities.…”

Fruit Flies in Biomedical Research

“…Many of these chemicals act on channels, receptors, and enzymes in the insect nervous system, some of which have been well studied in Drosophila (Hemingway et al 2004;RaymondDelpech et al 2005). Recently, molecular mechanisms underlying insecticide resistance have also being identified using Drosophila populations (Mateo et al 2014) or by generating transgenic fly strains that produce resistance genes from other species such as mosquitoes (Riveron et al 2013). Therefore, studies of insect nervous system genes, regardless of whether they are conserved or not, will provide additional functional insights and allow development of a list of potential targets for of new insecticides.…”

Impact of transposable elements on insect genomes and biology

“…Illustrating the exaptation of TE sequences into DNA with regulatory functions, different TE segments are retained in the vicinity and within the xenobiotic-metabolizing P450 genes that confer high resistance to the insecticide DDT [66,67]. Several additional reports suggest that TE insertions have been repeatedly and independently selected in the evolution of insecticide resistance in insects [66,68,69] [70,71 ]. Other TE insertions were recently shown to play a pivotal role in establishing regulatory networks as in D. miranda where copies of Helitron elements are responsible for dosage compensation over the X chromosome(s) [53 ].…”