Functional analysis of a natural mutational hotspot in the proximal promoter of a stress-response gene in Drosophila

Abstract

Mutational hotspots are common in disease genes and in complex genomic regions not amenable to sequencing by short reads technologies. However, it is still not clear what makes a particular genomic region more prone to mutations and whether the different mutations located in a hotspot are functionally equivalent. In this work, we have discovered and characterized in detail an insertional hotspot in the promoter region of a stress-response gene in the fruitfly Drosophila melanogaster. The nine transposable elements insertions described are clustered in a small 368 bp region and all belong to the same family of transposable elements: the roo family. Although the sequences of these insertions are highly similar, their molecular and functional consequences are different: only FBti0019985 insertion is associated with increased resistance to coldstress. Interestingly, the previously described insertional hotspot in the D. melanogaster genome was also located in the promoter of a stress response gene suggesting that selection may favour the maintenance of genetic variability in these genes.