Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila

Abstract

Variation in gene expression underlies inter-individual variability in immune response.However, the mutations responsible for gene expression changes remain largely unknown. In this work, we searched for transposable element insertions present at high population frequencies and located nearby immune-related genes in Drosophila melanogaster. We identified 12 insertions associated with allele-specific expression changes in immune-related genes. We showed that transgenically induced expression changes in most of these genes are associated with differences in survival to infection with the gram-negative bacteria Pseudomonas entomophila. We provide experimental evidence suggesting a causal role for five insertions in the allele-specific expression changes observed. Furthermore, for two insertions we found a significant association with increased tolerance to bacterial infection. Our results showed for the first time that polymorphic transposable element insertions from different families drive expression changes in genes that are relevant for inter-individual differences in immune response.

Diverse families of transposable elements affect the transcriptional regulation of stress-response genes in Drosophila melanogaster

“…We chose 11 TEs with at least one additional line of evidence to perform in vivo enhancer reporter assays (Table 4). We also included in Table 4 three TEs, tdn8 ( transpac ), FBti0020057 ( BS ) and FBti0018868 ( 297 ), which were previously tested in our laboratory (44). All these TEs contained three or more TFBMs/TFBSs, except FBti0019453 ( jockey ) that contained two and FBti0020057 ( BS ) that contained one (Table 4).…”

“…Experimental design indicates the region that was cloned in front of the reporter gene. We also included the data for three reporter assays performed previously in the lab (44).…”

“…We also generated transgenic flies to be used as positive controls for immunity (44), heat-shock (45) and for oxidative stress (46) (Supplementary Table S4). As negative controls, we generated transgenic flies with the empty vectors.…”

The interplay between developmental stage and environment underlies the adaptive effect of a natural transposable element insertion

“…Different types of mutations might differ in the complexity of their molecular and fitness-related effects, as has been suggested for transposable element (TE) induced mutations (9)(10)(11). TEs can affect gene structure and gene expression through many different molecular mechanisms (11,12), and some of these changes have been associated with adaptive phenotypes (13)(14)(15)(16)(17)(18)(19). In Drosophila, a dual role as enhancer and promoter of an adaptive insertion conferring tolerance to bacterial infection has been recently reported (19).…”

The transposable element-rich genome of the cereal pestSitophilus oryzae

“…TEs have also been frequently associated with insecticide-resistance in Drosophila species (Carareto et al 2014; Rostant et al 2012; Mateo et al 2014). In addition, population genetics studies suggested that more than 84 TE copies in D. melanogaster may play a positive role in fitness-related traits (Rech et al 2019), including xenobiotic resistance (Mateo et al 2014) and immune response to Gram-negative bacteria (Ullastres et al 2019).…”