%0 Journal Article %A François Mallard %A Viola Nolte %A Ray Tobler %A Martin Kapun %A Christian Schlötterer %T A simple genetic basis of adaptation to a novel thermal environment results in complex metabolic rewiring in Drosophila %D 2017 %R 10.1101/174011 %J bioRxiv %P 174011 %X Population genetic theory predicts that rapid adaptation is largely driven by complex traits encoded by many loci of small effect. Because large effect loci are quickly fixed in natural populations, they should not contribute much to rapid adaptation. To investigate the genetic architecture of thermal adaptation - a highly complex trait - we performed experimental evolution on a natural Drosophila simulans population. Transcriptome and respiration measurements revealed extensive metabolic rewiring after only ∼60 generations in a hot environment. Analysis of genome-wide polymorphisms identified two interacting selection targets, Sestrin and SNF4Aγ, pointing to AMPK, a central metabolic switch, as a key factor for thermal adaptation. Our results demonstrate that large-effect loci segregating at intermediate allele frequencies can allow natural populations to rapidly respond to selection. Because SNF4Aγ also exhibits clinal variation in various Drosophila species, we suggest that this large effect polymorphism is maintained by temporal and spatial temperature variation in natural environments. %U https://www.biorxiv.org/content/biorxiv/early/2017/08/11/174011.full.pdf