by Camille Berthelot, INSERM. Paris, FR
It has been hypothesized since the 1970s that phenotypic differences between mammals are largely driven by changes in gene regulation, rather than by differences in coding sequences. However, the evolution of gene regulatory programs remains poorly understood. Functional genomics assays have improved our understanding of mammalian gene regulation, and have enabled comparisons of regulatory programs between species to illuminate their evolution. I will present a series of related projects in which my collaborators and I used comparative functional genomics in model tissues to investigate (i) how mammalian gene regulation changes over time; (ii) how and when these changes in regulation result in modifications of gene expression; and (iii) whether we can identify selective changes in gene regulation related to phenotypic innovations in specific mammalian clades – in our case, the cancer-resistant mole rats. I will discuss the challenges of adapting phylogenetic modelling to identify candidate regulatory elements that have become selected for new functions amongst highly dynamic gene regulatory landscapes.