Widespread Occurrence of Dosage Compensation in Candida albicans

Abstract

The important human pathogen Candida albicans possesses an unusual form of gene regulation, in which the copy number of an entire specific chromosome or a large portion of a specific chromosome changes in response to a specific adverse environment, thus, insuring survival. In the absence of the adverse environment, the altered portion of the genome can be restored to its normal condition. One major question is how C. albicans copes with gene imbalance arising by transitory aneuploid states. Here, we compared transcriptomes from cells with either two copies or one copy of chromosome 5 (Ch5) in, respectively, a diploid strain 3153A and its representative derivative Sor55. Statistical analyses revealed that at least 40% of transcripts from the monosomic Ch5 are fully compensated to a disomic level, thus, indicating the existence of a genome-wide mechanism maintaining cellular homeostasis. Only approximately 15% of transcripts were diminished twofold in accordance with what would be expected for Ch5 monosomy. Another minor portion of approximately 6% of transcripts, unexpectedly, increased up to twofold and higher than the disomic level, demonstrating indirect control by monosomy. Array comparative genome hybridization revealed that only few out of approximately 500 genes on the monosomic Ch5b were duplicated, thus, not causing a global up regulation. Dosage compensation was confirmed with several representative genes from another monosomic Ch5a in the mutant Sor60. We suggest that C. albicans's unusual regulation of gene expression by the loss and gain of entire chromosomes is coupled with widespread compensation of gene dosage at the transcriptional level.

Tolerance to Caspofungin in Candida albicans Is Associated with at Least Three Distinctive Mechanisms That Govern Expression of FKS Genes and Cell Wall Remodeling

“…Presumably, in mutants with the monosomic Ch5, a single copy of either MID1 or CNB1 is upregulated to the disomic level, whereas in mutants carrying iso-Ch5R, three copies of each of these genes are downregulated to the disomic level. We previously reported transcriptional dosage compensation on the monosomic Ch5 (28). Transcriptional dosage compensation on a trisomic chromosome will be reported elsewhere (E. Rustchenko, unpublished data).…”

Chromosome 5 of Human Pathogen Candida albicans Carries Multiple Genes for Negative Control of Caspofungin and Anidulafungin Susceptibility

“…We also determined that, as could be expected, the abovementioned genes are downregulated on the monosomic Ch5 in the representative tolerant mutants that were generated by exposure to caspofungin, but these genes were not downregulated when Ch5 was reduplicated. This is significant, as genes on the monosomic Ch5 can be also upregulated to the disomic or above the disomic level (31).…”

Dosage compensation and inverse effects in triple X metafemales of Drosophila

“…Studies of gene expression in yeasts and mammals in disomics or trisomics have reported differing results as to compensation and trans-effects (e.g., refs. [35][36][37][38] vs. claims of primarily dosage effects of the varied genes (e.g., refs. 39, 40).…”