PT  - JOURNAL ARTICLE
AU  - Cedric A. Brimacombe
AU  - Jordan E. Burke
AU  - Jahan-Yar Parsa
AU  - Jessica N. Witchley
AU  - Laura S. Burrack
AU  - Hiten D. Madhani
AU  - Suzanne M. Noble
TI  - Chromatin rewiring mediates programmed evolvability via aneuploidy
AID  - 10.1101/407841
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 407841
4099  - http://biorxiv.org/content/early/2018/09/06/407841.short
4100  - http://biorxiv.org/content/early/2018/09/06/407841.full
AB  - Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis1, and yet specific aneuploidies can be adaptive during environmental stress2,3. Here, we identify a chromatin-based system for inducible aneuploidy in a human pathogen. Candida albicans utilizes chromosome missegregation to acquire resistance to antifungal drugs4,5 and for ploidy reduction after mating6. 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 kinase7, a key regulator of chromosome segregation1. Expression of this variant controls the rates of aneuploidy and antibiotic resistance in this species. Moreover, 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.