The Role of transposable elements in regulatory networks in response to stress

Rovira Castellà, Quirze
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Transposable elements (TEs) are mobile DNA sequences that have the ability to jump from one location of the genome to another and create copies of them during the process. Although their activity can create mostly harmful mutation, it also represent an important source of genetic variation that have been shown to rewire and fine-tune regulatory networks. Stress response mechanisms are highly conserved across organisms and a major target of natural selection. Despite the latest advances in evolutionary biology, adaptation process remains poorly understood. Therefore, studying stress pathways provide a great opportunity to study how adaptive processes occur. In this study we aim to identify genome-wide putatively adaptive TEs that are candidates to modulate stress response by the addition of stress response elements (SREs) in the promoter of Drosophila melanogaster genes. We combine bioinformatics and population genetics approaches to discard SREs found by chance and select TEs having SREs that are more likely to be involved in stress response. We found 3,381 TEs out of 5,416 annotated TEs that contain at least one SRE. Because only TEs inserted in the promoter region are likely to have a biological impact in the gene modulation we reduce our dataset to 406 TEs. Moreover, we select TEs present at high frequency in the populations since they are more likely to be adaptive. Finally, our curated dataset contain 108 TEs with at least one SRE, inserted at a promoter region of a gene and at high frequency in at least one of the 8 worldwide studied populations. Out of this list we in silico validate 18 TEs thanks to modENCODE project and other chromatin immuneprecipitation studies. Additionally, we analyzed the promoter of the 127 genes nearby the 108 TEs. The function of 22 out of this list was related to stress by genome wide association studies and gene ontology term annotations. Eighty-five TEs add preexisting or novel SREs while other 26 introduce SREs to the regions without any previous SREs. Having several SREs make the promoter region and/or the TE more likely to have an impact on the gene expression. Seventy-three TEs out of the 108 TEs contain more than one SRE and hence are more likely to be involved in stress response regulation. Our final candidate list is the starting point to functionally analyze the role of these putatively adaptive TEs in stress response ​
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