Exploring Astyanax mexicanus as a model for unraveling genotype-environment interactions and metabolic adaptations

The Mexican tetra (Astyanax mexicanus), comprising the river-dwelling surface fish and multiple independently evolved cave populations, has emerged as a powerful model for studying the complex interplay between genotype and environment in shaping organismal phenotypes including metabolism. Cavefish have adapted to the extreme conditions of subterranean life-marked by perpetual darkness and limited food availability-through a suite of phenotypes, including eye and pigment loss, enhanced sensory systems, altered sleep and feeding behaviors and remarkable metabolic remodeling. This Perspective brings together major advances over the past two decades in our understanding of these phenotypes, with a focus on the metabolic adaptations used by cavefish. Here we also highlight the experimental tools, web tools and other resources that are expanding the utility of A. mexicanus for mechanistic and translational research. A comparison with other model organisms used in metabolic studies is also included. Finally, we opine how a precision medicine approach to cavefish research can provide insights into human health and disease.