Understanding the genetic properties of adaptive trait evolution is a
fundamental crux of biological inquiry that links molecular processes to
biological diversity. Important uncertainties persist regarding the
genetic predictability of adaptive trait change, the role of standing
variation, and whether adaptation tends to result in the fixation of
favored variants. Here, we use the recurrent evolution of enhanced
ethanol resistance in Drosophila melanogaster during this species'
worldwide expansion as a promising system to add to our understanding of
the genetics of adaptation. We find that elevated ethanol resistance has
evolved at least three times in different cooler regions of the species'
modern range - not only at high latitude but also in two African high
altitude regions - and that ethanol and cold resistance may have a
partially shared genetic basis. Applying a bulk segregant mapping
framework, we find that the genetic architecture of ethanol resistance
evolution differs substantially not only between our three resistant
populations, but also between two crosses involving the same European
population. We then apply population genetic scans for local adaptation
within our quantitative trait locus regions, and we find potential
contributions of genes with annotated roles in spindle localization,
membrane composition, sterol and alcohol metabolism, and other
processes. We also apply simulation-based analyses that confirm the
variable genetic basis of ethanol resistance and hint at a moderately
polygenic architecture. However, these simulations indicate that
larger-scale studies will be needed to more clearly quantify the genetic
architecture of adaptive evolution, and to firmly connect trait
evolution to specific causative loci.