SUMMARY In the study of disease, the polygenic factors that lead to genetic adaptation in species, essentially who will be asymptomatic while under environmental stressors, mostly remain undiscovered. Without a comparative understanding of these unique features by cell type, that evolution has preserved, our efforts to more broadly implement precision medicine will be limited in multiple phenotypes. One of the most promising applications of evolutionary medicine has been the use of divergent animal models to deconstruct and uncover fundamental concepts of biological organization in great detail. The Mexican cavefish, Astyanax mexicanus provides a rapidly growing model system to apply principles of evolutionary medicine to study trait variation. We have implemented a toolbox of genetic tools that allow for functional interrogation of various traits in the Mexican cavefish, but key resources are missing. This model species consists of surface and cavefish populations that possess natural trait differentiation, often displaying genetic adaption associated with environmental change, without impacting health or longevity. The objectives of our studies are to generate three tiers of community requested resources: high-quality surface and cavefish genome assemblies, using powerful single-cell sequencing technology a cell atlas with differentiating gene expression data sets and targeted gene reporter constructs coupled with a spatial understanding of their gene regulatory effects. This compendium of resource data and methodology can serve a large community wishing to test various hypotheses of adaptation in this species and others. Our proposed research objectives are significant in that they will contribute comparative gene networks that reveal novel differences with a growing assemblage of gene candidates for human diseases.