Why some animal species are more sensitive than others to man-made chemicals is a major scientific puzzle: with increasing relevance in the light of the Anthropocene. Animals exhibit conserved and divergent sensitivities to external stimuli. Yet, the extent of genetic variation underlying such dissimilar responses is far from fully assessed; nor is the contribution of evolutionary processes promoting disparate responses.

Thus, taking this physiological range in consideration a simple, yet intrinsically complex question, arises: how do man-made chemicals "exploit" the genetic/physiological animal biodiversity? To address such a broad question, we must consider a Systems Toxicology approach: from genome diversity, at an ecosystem scale, to the physiological integration of the observed variability, at a species level, notably in the context of human-derived environmental settings. Metazoan endocrine systems serve as a prime model to address such issues: they encompass an intricate network of signalling cascades, that when disturbed lead to episodes of disruption with physiological impairment. A flurry of studies has disclosed the harmful effects resulting from the environmental exposure to Endocrine Disrupting Chemicals (EDCs), particularly in aquatic environments. EDCs act in many cases as high-affinity ligands of transcription factors, the Nuclear Receptors (NRs). This ability to be ligand-activated is of crucial ecological relevance. Several studies have revealed NR exploitation (agonist/antagonist) by EDCs, with dire endocrine results. Yet, a variable NR gene repertoire has been found in different Metazoan lineages, mostly with unknown repercussions in endocrine function. Decisively also, is whether orthologous receptors remained functionally stable over evolutionary time scales or with what consequences in disruption processes? Besides from a handful of model species, our knowledge remains extremely sparse. Thus, the key topic of EvoDis is to use NR-mediated disruption as a case-study to address the Metazoan taxonomic scope of man-made chemical "exploitation?. Acting at the frontier of Evolutionary Biology and Toxicology, we will: 1) investigate and provide a fine-scale mapping of NRs in Metazoan lineages combining extensive database mining with transcriptomic approaches of phyla covering pre-bilateria, protostome and deuterostome species; 2) determine the binding profile of NRs to a collection of EDCs in evolutionary and ecosystem representative species, through functional genomics assays; and finally 3) determine the physiological and molecular signatures of in vivo EDC exposure through next gen sequencing tools at evolutionary informative phyla. EvoDis puts into context the role of NRs, sculpted by eons of evolution, in endocrine disruption processes, which would be impossible to reveal with model species. We expect the findings from EvoDis to pave the way for the development of multi-specific sensor tools to monitor EDC compounds.