Opposing Copy Number Variation Dynamics Shape Adaptation to Glucose and Galactose in Diploid Yeast

How do structural variants and point mutations jointly shape long-term adaptation in constant environments? We evolved six replicate diploid Saccharomyces cerevisiae populations for 1,200 generations in glucose or galactose and quantified fitness every 300 generations under controlled history manipulations. Whole-genome sequencing across four time points per population revealed that adaptation was dominated by copy-number variations (CNVs), with single-nucleotide polymorphisms (SNPs) rare across lines and time. CNVs were strongly environment-specific: glucose-evolved populations showed early, widespread telomeric deletions encompassing carbon-use modules, followed by a reduction of deletion burden and appearance of compensatory duplications; galactose-evolved populations accumulated persistent telomeric and sub-telomeric duplications.

Many of the same genes were targeted in opposite directions across environments (deleted in glucose, duplicated in galactose), linking structural remodeling to divergent physiological strategies. History-dependent fitness costs were pronounced early for glucose-evolved lines after galactose preculture but diminished by ∼900 generations, whereas costs deepened in galactose-evolved lines after glucose preculture. A linear modeling framework identified ancestral fitness as the strongest predictor of evolved fitness, with evolutionary time contributing modestly and preconditioning/recovery exerting subtle, time-dependent effects. Together, these results argue that predictable, environment-specific CNV trajectories, rather than SNP accumulation, underlie the bulk of adaptation, and that structural variation operates within constraints imposed by the starting genotype and regulatory architecture.