Males and females in many animals are strikingly different in behaviour, physiology, shape and form. In humans, rates of ageing and disease incidence vary markedly between the sexes. Moreover, sex differences in response to medical therapies and treatments have recently become an area of major biomedical concern. Because there are very few sex-limited genes, sex differences are largely a product of contrasting gene expression patterns between males and females4. Despite their ubiquity and clear biomedical importance, the evolutionary causes of sex differences in gene expression remain essentially unknown and pose a fundamental problem for biologists: How do sex differences evolve given that the sexes largely share the same genome?My research addresses this fundamental question using two approaches: (1) a data-driven, large-scale phylogenetic approach, and (2) an experimental manipulation of chromosome dose in Drosophila melanogaster. The results from this project will create comprehensive understanding of sex-specific gene regulation and evolution. This broad research has important implications for medical, developmental and evolutionary studies of sex differences and addresses a key aim, as identified by the European Commission, for research excellence in Horizon 2020.