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Merenciano, M.

Publications and source records attributed to Merenciano, M..

6 recordsLinked to original sources

Transposable elements modulate gene expression in response to oxidative stress in Drosophila suzukii

Transposable elements (TEs) are major contributors to genomic and regulatory variation and can influence the expression of nearby genes in response to environmental stress. The invasive fruit fly Drosophila suzukii, whose genome is composed of nearly 50% TE-derived sequences, provides an excellent model to investigate the regulatory impact of TEs on stress responses. Although previous studies found no global association between TEs and oxidative stress transcriptomic response in this species, the effects of individual TE insertions remain largely unexplored. Here, we investigated the role of two polymorphic intronic TE insertions, Mrp4-TE and inaE-TE, located within genes implicated in the oxidative stress response in D. melanogaster. Using wild-type strains of D. suzukii, we assessed the effect of these insertions on gene expression following oxidative stress induced by paraquat exposure. We found that their corresponding nearby genes Mrp4 and inaE were upregulated after paraquat treatment and that this response was significantly stronger in flies carrying the corresponding TE insertions. Allele-specific expression analyses further showed that the alleles containing the TE insertions exhibited a tendency towards higher expression levels than alleles lacking the insertions, both under control and oxidative stress conditions, supporting a cis-regulatory effect. In addition, Mrp4-TE was associated with increased sensitivity to oxidative stress. Together, our results provide the first evidence that TE insertions can modulate oxidative stress-responsive gene expression in D. suzukii. These findings highlight the importance of investigating individual TE insertions to understand the genetic and regulatory mechanism underlying stress responses, adaptation, and invasion success in this species.

genomics↗

Transposable elements drive phenotypic variation and shape the response to environmental changes in Drosophila melanogaster

Transposable elements (TEs) are ubiquitous repetitive DNA sequences that can mobilise within genomes and may modulate gene expression in an environment-dependent manner. TEs and the safeguarding epigenetic machinery targeting them, can be tuned by environmental fluctuations to influence gene expression by inducing genomic, epigenetic, and transcriptomic changes. Yet, the degree to which TE-driven molecular diversity translate into inter-individual phenotypic variation vs accumulating without any phenotypic consequences remains unclear. Here, we used five populations of genetically engineered Drosophila melanogaster flies that carry variable TE content but share an otherwise identical genetic background to test the phenotypic consequences of the early stages of TE accumulation. Phenotypic screenings across 17 traits (fertility-related traits, life-history traits and stress resistance tests) revealed significant differences between the populations (e.g. reduced hatchability). We also observed a notable increase in intra-population phenotypic variation for the heavily TE-burdened populations across a wide panel of traits. These results suggest considerable TE-driven inter- and intra-population phenotypic variation. Further investigation revealed that variable TE contents can influence the response to environmental changes, positioning TEs as drivers of environmentally-induced phenotypic variation in a system deprived of other sources of genetic variation. These results provide empirical evidence that TEs contribute to the heterogeneity of the environmental response and therefore represent an underlying mechanism of phenotypic variation.

evolutionary biology↗

Exploring the role of transposable elements to sex gap in longevity in Drosophila species

In Drosophila, like in many other animal species, females tend to live longer than males, a phenomenon known as sex gap in longevity (SGL). One possible explanation for this phenomenon could be related to the activity of transposable elements (TE), which may be present at higher levels in the heterogametic sex. TE activity is normally repressed by epigenetic mechanisms, but this regulation weakens with age. Sex chromosomes, such as the Y chromosome, are enriched in TEs, and age-related TE activity may therefore be more pronounced in older males than in older females, likely affecting longevity patterns. Using three Drosophila species, we show that SGL varies naturally among wild-type populations, reflecting both intra-and inter-species differences. Transcriptomic data revealed increased age-related TE expression in D. melanogaster and D. suzukii flies, but not in D. simulans. Moreover, we observed a higher number of upregulated TE copies in older males compared to older females across all the three species tested. Additionally, we detected an increase in TE-chimeric transcript generation in some aged samples, particularly in D. suzukii males. Finally, the replacement of the Y chromosome between strains with different SGL led to a progressive reduction in male lifespan and increased TE transcriptional release over generations, suggesting a Y chromosome important role in male longevity. Our work highlights the importance of investigating the role of TEs to better understand differences in longevity between sexes and across different species.

genomics↗

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

Establishing causal links between adaptive mutations and their ecologically relevant phenotypes is key to understanding the process of adaptation, a central goal in evolutionary biology that is also relevant for conservation biology, medicine and agriculture. Although progress has been made, the number of causal adaptive mutations identified so far is still limited as gene by gene, and gene by environment interactions, among others, complicates linking genetic variation with its fitness-related effects. Transposable elements, often ignored in the quest for the genetic basis of adaptive evolution, are known to be a genome-wide source of regulatory elements across organisms that at times can lead to adaptive phenotypes. In this work, we combine gene expression, in vivo reporter assays, CRISPR/Cas9 genome editing, and survival experiments to characterize in detail the molecular and phenotypic consequences of a natural Drosophila melanogaster transposable element insertion: the roo solo-LTR FBti0019985. This transposable element provides an alternative promoter to the transcription factor Lime, involved in cold- and immune-stress responses. We found that the effect of FBti0019985 on Lime expression depends on the interplay between the developmental stage and the environmental conditions. We further establish a causal link between the presence of FBti0019985 and increased survival to cold- and immune-stress. Our results exemplify how several developmental stages and environmental conditions need to be considered to characterize the molecular and functional effects of a genetic variant, and add to the growing body of evidence that transposable elements can induce complex mutations with ecologically relevant effects.

evolutionary biology↗

Natural transposable element insertions drive expression changes in genes underlying Drosophila immune response

BackgroundVariation in gene expression underlies interindividual variability in relevant traits including immune response. However, the genetic variation responsible for these gene expression changes remain largely unknown. Among the non-coding variants that could be relevant, transposable element insertions are promising candidates as they have been shown to be a rich and diverse source of cis-regulatory elements. ResultsIn this work, we used a population genetics approach to identify transposable element insertions likely to increase the tolerance of Drosophila melanogaster to bacterial infection by affecting the expression of immune-related genes. We identified 12 insertions associated with allele-specific expression changes in immune-related genes. We experimentally validated three of these insertions including one likely to be acting as a silencer, one as an enhancer, and one with a dual role as enhancer and promoter. The direction in the change of gene expression associated with the presence of several of these insertions was consistent with an increased survival to infection. Indeed, for one of the insertions, we showed that this is the case by analyzing both natural populations and CRISPR/Cas9 mutants in which the insertion was deleted from its native genomic context. ConclusionsWe showed that transposable elements contribute to gene expression variation in response to infection in D. melanogaster and that this variation is likely to affect their survival capacity. Because the role of transposable elements as regulatory elements is not restricted to Drosophila, TEs are likely to play a role in immune response in other organisms as well.

evolutionary biology↗

Stress response, behavior, and development are shaped by transposable element-induced mutations in Drosophila

Mapping genotype to phenotype is challenging because of the difficulties in identifying both the traits under selection and the specific genetic variants underlying these traits. Most of the current knowledge of the genetic basis of adaptive evolution is based on the analysis of single nucleotide polymorphisms (SNPs). Despite increasing evidence for their causal role, the contribution of structural variants to adaptive evolution remains largely unexplored. In this work, we analyzed the population frequencies of 1,615 Transposable Element (TE) insertions in 91 samples from 60 worldwide natural populations of Drosophila melanogaster. We identified a set of 300 TEs that are present at high population frequencies, and located in genomic regions with high recombination rate, where the efficiency of natural selection is high. The age and the length of these 300 TEs are consistent with relatively young and long insertions reaching high frequencies due to the action of positive selection. Indeed, we, and others, found evidence of selective sweeps and/or population differentiation for 65 of them. The analysis of the genes located nearby these 65 candidate adaptive insertions suggested that the functional response to selection is related with the GO categories of response to stimulus, behavior, and development. We further showed that a subset of the candidate adaptive TEs affect expression of nearby genes, and five of them have already been linked to an ecologically relevant phenotypic effect. Our results provide a more complete understanding of the genetic variation and the fitness-related traits relevant for adaptive evolution. Similar studies should help uncover the importance of TE-induced adaptive mutations in other species as well.

evolutionary biology↗