To date, only a limited number of TE insertions in Drosophila have been unequivocally connected to their relevant fitness effects: an Accord LTR retrotransposon, a Doc non-LTR retrotransposon, a Bari1 transposon, and a pogo transposon, an invader-4 an LTR retrotransposon and a roo element an LTR retrotransposon.
Daborn and colleagues identified an Accord element inserted in a gene involve in the detoxification of multiple insecticides. The presence of this TE insertion was associated with increased Cyp6g1 expression and increased resistance to insec- ticides such as DDT. Further analyses demonstrated that this Accord element carries regulatory sequences that specifically increase Cyp6g1 expression in tissues important for detoxification. When several D. melanogaster strains were analyzed, it was discovered that successive mutations, including gene duplications and additional TE insertions, have occurred in the Cyp6g1 locus. Interestingly, there is an increase in resistance level for at least three of the five mutant alleles described, suggesting that this allelic succession could have been driven by selection removing fitness costs associated with the preceding resistance allele.
Similarly, an allelic series affecting the gene region in which the adaptive Doc1420, FBti0019430, is inserted has also been reported. Aminetzach and colleagues first described the putatively adaptive insertion of this Doc element into the coding region of CHKov1. This insertion generates two sets of altered transcripts, and it is associated with increased resistance to an organophosphate insecticide (AZM). However, the authors estimated that the allele containing the Doc1420 insertion was 90,000 years old. Because insecticides were first used only a few decades ago, the original reasons for the fast evolution and persistence in natural populations of the Doc1420-containing allele must be related to some other phenotypic effect. As anticipated by Aminetzach and colleagues, polymorphisms in the CHKov1 gene region were later found to be associated with a different phenotype: resistance to viral infection. Magwire and colleagues showed that although the truncation of CHKov1 coding region by insertion of the Doc1420 element confers resistance to the sigma virus, an allele containing two duplications resulting in three copies of the truncated allele of both CHKov1 and CHKov2 (one of which is also truncated) caused increased resistance.
Recently, a third TE insertion has been connected to its ecologically relevant fitness effect. A full-length Bari1 insertion was identified as being putatively adaptive based on its population frequency and on the detection of a selective sweep in its flanking regions. This insertion, named Bari-Jheh FBti018880, is located in the intergenic region of juvenile hormone epoxy hydrolase (Jheh) genes, and it was found to affect the level of expression of its two nearby genes. Phenotypic effects consistent with the reduced level of expression of Jheh3 and Jheh2 genes were also found. However, the phenotypic effects identified, reduced viability and increased developmental time, are likely to represent the cost of selection of this insertion, whose adaptive effect remains unknown. A detailed analysis of the Bari-Jheh sequence revealed that this TE adds extra antioxidant response elements (AREs) to the upstream regions of Jheh2 and Jheh1 genes. AREs are highly conserved sequences, found in organisms from flies to humans, which mediate response to stress by upregulating the expression of downstream genes. As expected, we found that flies with Bari-Jheh showed increased levels of expression of Jheh2 and Jheh1 under oxidative stress conditions and increased resistance to this stress. Furthermore, we also found that TEs other than Bari-Jheh add extra AREs to the upstream region of several genes, suggesting a more general role of Bari elements in response to oxidative stress.
Finally, a pogo transposon, FBti0019627, has been shown to mediate resistance to xenobiotics. This TE affects the polyadenylation signal choice of its nearby gene CG11699. As a result, only one of the two CG11699 transcripts is produced and the expression of CG11699 increases. Mateo et al. further showed that increased CG11699 expression leads to increased aldehyde dehydrogenase III enzymatic activity that results in increased resistance to xenobiotic stress.
It also has been found that flies with, a invader 4 retrotransposon FBti0019386 insertion, had a shorter developmental time and were more sensitive to stress, which are likely to be the adaptive effect and the cost of selection of this mutation, respectively. Interestingly, these phenotypic effects are not consistent with a role of FBti0019386 in temperate adaptation as has been previously suggested.
Finally, one of the transposable element insertions, named FBti0019985, provides an alternative transcription start sites that drives expression of CG18446, a candidate stress response gene. FBti0019985 was associated with cold-stress tolerance.
These six examples show the variety of molecular mechanisms underlying TE-driven adap- tation: from adding tissue-specific or response-to-stress regulatory regions, to the generation of new transcripts, to inactivation of genes. However, the number of adaptive TEs whose adaptive phenotypic effects are known is still too small, and many more TEs need to be characterized to get a more general picture of the adaptive process.
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