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

Abstract

Adaptation to new environments arises from multiple forms of genetic variation, including single-nucleotide polymorphisms (SNPs) and structural variants such as copy number variations (CNVs). Although both mutation classes have been implicated in evolutionary change, their relative contributions during adaptation remain incompletely understood and may depend strongly on environmental context. Here we investigated genome evolution during experimental adaptation of diploid Saccharomyces cerevisiae populations propagated for 1200 generations in two alternative carbon sources, glucose or galactose. Whole-genome sequencing of replicate populations at multiple evolutionary time points revealed relatively few SNPs but widespread copy number variation across the genome. Strikingly, CNV dynamics differed markedly between environments. Populations evolved in glucose exhibited extensive early deletions followed by later genomic remodeling that reduced the overall deletion burden. In contrast, populations evolved in galactose accumulated persistent subtelomeric duplications throughout the experiment. Many loci displayed opposing copy number changes in the two environments, with genes deleted during evolution in glucose frequently duplicated during evolution in galactose. These contrasting trajectories indicate that structural genomic changes repeatedly arise during adaptation and that their direction and persistence depend strongly on environmental conditions. Together, our results illustrate how distinct genomic routes can emerge during adaptation of genetically identical populations and highlight the importance of considering multiple classes of mutations when studying evolutionary responses to environmental change. Impact statementThis study demonstrates that copy number variations (CNVs), rather than single-nucleotide polymorphisms, dominate genome evolution during adaptation of diploid Saccharomyces cerevisiae to alternative carbon sources. By evolving genetically identical populations in glucose and galactose, the work reveals that environmental context drives strikingly opposing CNV trajectories, widespread deletions in glucose and persistent duplications in galactose, often targeting the same genomic loci in opposite directions. These findings provide direct evidence that structurally mediated gene dosage changes are a primary and environment-dependent mechanism of adaptation, reshaping metabolic networks and specialization strategies. More broadly, the study challenges the prevailing SNP-centric view of adaptive evolution and highlights CNVs as a predictable and major axis of genome remodeling in microbial systems.