GSE122037
Chromatin rewiring mediates programmed evolvability via aneuploidy
Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis, and yet specific aneuploidies can be adaptive during environmental stress.  Here, we identify a chromatin-based system for inducible aneuploidy in a human pathogen. Candida albicans utilizes chromosome missegregation to acquire resistance to antifungal drugs and for ploidy reduction after mating.  We discovered that the ancestor of C. albicans and two related pathogens evolved a variant of histone H2A that lacks the conserved phosphorylation site for Bub1 kinase, a key regulator of chromosome segregation. Using engineered strains, we show that expression of this variant controls the rates of aneuploidy and antibiotic resistance in this species.  Moreover, whole genome chromatin precipitation analysis reveals that CENP-A/Cse4, the histone H3 that specifies centromeres, is depleted from tetraploid mating products and virtually eliminated from cells exposed to aneuploidy-promoting cues.  Thus, changes in chromatin regulation can confer the capacity for rapid evolution in eukaryotes.  Overall design: ChIP-seq in diploid and tetraploid C. albicans to understand the role of histone variants in chromosome loss.