Strain background of interacts with to alter phenotypic switching.

The genetic background between strains of a single species and within a single strain lineage can significantly impact the expression of biological traits. This genetic variation may also reshape epigenetic mechanisms of cell identity and environmental responses that are controlled by interconnected transcriptional networks and chromatin-modifying enzymes. Histone deacetylases, including sirtuins, are critical regulators of chromatin state and have been directly implicated in governing the phenotypic transition between the 'sterile' white state and the mating-competent opaque state in a common fungal commensal and pathogen of humans. Here, we found that a previously ambiguous role for the sirtuin in phenotypic switching is likely linked to the genetic background of mutant strains produced in the RM lineage of SC5314. mutants in a specific lineage of BWP17 displayed increased frequencies of switching to the opaque state compared to the wild-type. Loss of in other SC5314-derived backgrounds, including newly constructed BWP17 Δ/Δ mutants, failed to recapitulate the increased white-opaque switching frequencies observed in the original BWP17 Δ/Δ mutant background. Whole-genome sequencing revealed the presence of multiple imbalanced chromosomes and large loss of heterozygosity tracts that likely interact with to increase phenotypic switching in this BWP17 Δ/Δ mutant lineage. These genomic changes are not found in other SC5314-derived Δ/Δ mutants that do not display increased opaque cell formation. Thus, complex karyotypes can emerge during strain construction that modify mutant phenotypes and highlight the importance of validating strain background when interpreting phenotypes.