DescriptionAdaptation is the process by which organisms respond to and become more fit for the environment they live in. This process is driven by mutations to the genome that create phenotypic variation in a population upon which natural selection can act. While links between mutations and phenotypes are sometimes obvious, how these relate to fitness is often less clear. Mutations in protein coding regions can produce adaptive phenotypes, but so too can mutations that change the timing, amount, or location of expression of genes. However, the extent that mutations that affect these molecular phenotypes contribute to adaptation is unknown. In this work, we perform high-throughput, genome-wide studies of an experimental evolution system to study how changes to RNA abundance, translation of these RNAs, and their effects at the metabolic level contribute to adaptation in a system with defined fitness and genetic changes but few links between them. We show that despite varying sets of mutations, similar gene expression patterns emerge in the system, suggesting that the shaping of a particular expression profile can be a mode of adaptation to a novel environment. We further show that changes to gene expression profiles can exert their effects at the metabolic level. Overall, our strategy of relating mutations, expression changes, and their effects on the metabolome provides a more complete picture of how, at the molecular level, organisms adapt to their environment.