Strength of selection potentiates distinct adaptive responses in an evolution experiment with outcrossing yeast

Selection intensity is expected to influence the magnitude and genetic architecture of adaptive responses, yet it is rarely evaluated as a standalone variable in experimental evolution studies. Here, we evolved outcrossing populations of Saccharomyces cerevisiae for ∼200 generations across a spectrum of environmental stress from zero to moderate to high ethanol exposure, to examine how genomic responses vary with stress intensity. Across treatments, adaptation proceeded through many subtle allele and haplotype frequency shifts rather than large changes at single loci, consistent with a highly polygenic response. At loci associated with ethanol adaptation, the high stress treatment led to larger allele frequency changes compared with the moderate or no ethanol stress treatments, with the genomic architecture of adaptation becoming increasingly polygenic as selection intensity decreased. Moderate and high stress conditions engaged partially distinct biological pathways, indicating that selection intensity shapes both the magnitude and targets of adaptive change. Within this stress continuum, we also observed substantial, ongoing adaptation in control populations despite extensive prior domestication. Many alleles associated with this adaptation showed reduced or absent responses under ethanol stress, consistent with antagonistic pleiotropy. Consequently, laboratory adaptation can represent a major component of evolutionary change and may confound treatment-specific inferences when not explicitly accounted for. Broadly, our results demonstrate that selection intensity structures adaptive responses in experimental evolution and that continued laboratory adaptation remains an important force in these studies. Our findings underscore the importance of clearly-defined controls and careful consideration of selection intensity when interpreting or comparing across experimental evolution studies.