Population dynamics of microRNA regulation: biomedical applications

Gene regulatory interactions form the backbone of any biological process. Indeed, it is well established that selection maintains regulatory sites. MicroRNAs are post-transcriptional gene regulators that target transcripts by pairwise complementarity at specific target sites. In a recent study I explored the evolutionary dynamics of microRNA target sites in the fruit fly. By developing a novel population genetics mutation model, I detected selection against maternal microRNA target sites in maternal transcripts. I suggested that this pattern of 'target avoidance' is a consequence of gene regulatory conflicts and that this may be a widespread evolutionary phenomenon. In a pilot study I observed that target avoidance also happens in human populations. I also showed that disease-associated regulatory interactions can be inferred by detecting target-avoidance events.

This proposal aims to develop a population genetics model of microRNA target site evolution based on my recent findings and to apply it to the analysis of human diseases. This project will also facilitate the establishment of collaborative links in the emerging field of evolutionary biomedical sciences.