Dissecting Gene Expression Changes Accompanying a Ploidy-Based Phenotypic Switch.
Aneuploidy, a state in which the chromosome number deviates from a multiple of the haploid count, significantly impacts human health. The phenotypic consequences of aneuploidy are believed to arise from gene expression changes associated with the altered copy number of genes on the aneuploid chromosomes. To dissect the mechanisms underlying altered gene expression in aneuploids, we used RNA-seq to measure transcript abundance in colonies of the haploid Saccharomyces cerevisiae strain F45 and two aneuploid derivatives harboring disomies of chromosomes XV and XVI. F45 colonies display complex "fluffy" morphologies, while the disomic colonies are smooth, resembling laboratory strains. Our two disomes displayed similar transcriptional profiles, a phenomenon not driven by their shared smooth colony morphology nor simply by their karyotype. Surprisingly, the environmental stress response (ESR) was induced in F45, relative to the two disomes. We also identified genes whose expression reflected a nonlinear interaction between the copy number of a transcriptional regulatory gene on chromosome XVI, DIG1, and the copy number of other chromosome XVI genes. DIG1 and the remaining chromosome XVI genes also demonstrated distinct contributions to the effect of the chromosome XVI disome on ESR gene expression. Expression changes in aneuploids appear to reflect a mixture of effects shared between different aneuploidies and effects unique to perturbing the copy number of particular chromosomes, including nonlinear copy number interactions between genes. The balance between these two phenomena is likely to be genotype- and environment-specific.
Pacific Northwest Research Institute, Seattle, Washington 98122.
Gareth A
GA
Cromie
Pacific Northwest Research Institute, Seattle, Washington 98122.|Institute of Medical Biology, Agency for Science, Technology and Research, Singapore.
Zhihao
Z
Tan
Molecular and Cellular Biology Program, University of Washington, Seattle, Washington.
Michelle
M
Hays
Pacific Northwest Research Institute, Seattle, Washington 98122.
Eric W
EW
Jeffery
Pacific Northwest Research Institute, Seattle, Washington 98122 aimee.dudley@gmail.com.|Molecular and Cellular Biology Program, University of Washington, Seattle, Washington.
Aimée M
0000-0003-3644-0625
AM
Dudley
D000782:Aneuploidy; D015825:Chromosomes, Fungal / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006238:Haploidy; D006801:Humans; D059785:Karyotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics*
RNA-seq; aneuploidy; colony morphology; gene expression