The G?E concept, in which genotype ? environment interactions bring about the phenotype, is widely used to describe biological phenomena. We propose to extend the initial notion of the concept, replacing G by ?inheritance system?. This system, comprised of both genome and epigenome components, collectively interacts with the environment to shape the development of a phenotype. In the case of the human blood fluke Schistosoma mansoni, responsible for intestinal bilharzia, the phenotypic trait that is most relevant to global health is infection success. Taking a systems biology view we show how genetic and epigenetic interactions result in ephemeral, but also heritable, phenotypic variations that are important for infection success. ; proof ; Peer reviewed