Adaptive responses to antifungal selection depend on dose and drug combination in experimentally evolved yeast

In Saccharomyces cerevisiae evolved for >50 generations, antifungal genomic responses show little overlap across drug concentrations and combinations, with additivity expectations departing.

• Why it matters: Natural antifungal exposure varies in intensity and drug composition, but lab evolution often tests single, fixed stressors, leaving theory on compounded selection largely untested.
• What they did: Twelve replicate populations from a genetically diverse ancestor were evolve-and-resequenced under low or high caspofungin or clotrimazole alone, their combination, or no drug, using pooled-population sequencing at three timepoints.
• The result: Candidate loci rarely overlapped across environments; FKS1 appeared in all caspofungin treatments, while a putative gain of the ERG11-containing chromosome VIII occurred in 9 of 12 high-clotrimazole populations, with little fitness cost in drug-free medium.