AbstractMost organismal phenotypes have a polygenic basis, which enables adaptive phenotypic responses on ecological time scales. While adaptive phenotypic changes are highly parallel in replicate populations, this does not apply to the contributing loci. In particular for small populations, the same phenotypic shift can be fueled by different sets of alleles at alternative loci (genetic redundancy). Although this phenomenon is empirically well supported, the molecular basis of the genetic redundancy is not yet understood. To fill this gap, we compared the heterogeneity of the evolutionary transcriptomic and metabolomic response in tenDrosophila simulanspopulations which evolved parallel high-level phenotypic changes in a novel temperature environment but used different allelic combinations of alternative loci. We showed that the metabolome evolved more parallel than the transcriptome, confirming a hierarchical organization of molecular phenotypes. Different sets of genes responded in each evolved population but led to the enrichment of similar biological functions and a consistent metabolic profile. Since even the metabolomic response was still highly heterogeneous across evolved populations, we propose that selection may operate on pathways/networks.