Nonlinear fitness consequences of variation in expression level of a eukaryotic gene

Levels of gene expression show considerable variation in eukaryotes, but no fine-scale maps have been made of the fitness consequences of such variation in controlled genetic backgrounds and environments. To address this, we assayed fitness at many levels of up- and down-regulated expression of a si...

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Bibliographic Details
Published in:Molecular biology and evolution 2013-02, Vol.30 (2), p.448-456
Main Authors: Rest, Joshua S, Morales, Christopher M, Waldron, John B, Opulente, Dana A, Fisher, Julius, Moon, Seungjae, Bullaughey, Kevin, Carey, Lucas B, Dedousis, Demitri
Format: Article
Language:English
Subjects:
Biological Evolution
Biosynthesis
Carrier Proteins - genetics
Carrier Proteins - metabolism
Discoveries
Environment
Eukaryotes
Fitness
Fitness function
Gene expression
Gene Expression Regulation, Fungal
Gene mapping
Gene regulation
Gene regulatory evolution
Genetic diversity
Genetic Fitness
Genetics
Genomics
Metabolisme
Osmotic stress
Protein Binding
Regulació genètica
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Serine C-Palmitoyltransferase - genetics
Serine C-Palmitoyltransferase - metabolism
Sphingolipids
Stress response
Yeast
Yeasts
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Summary:Levels of gene expression show considerable variation in eukaryotes, but no fine-scale maps have been made of the fitness consequences of such variation in controlled genetic backgrounds and environments. To address this, we assayed fitness at many levels of up- and down-regulated expression of a single essential gene, LCB2, involved in sphingolipid synthesis in budding yeast Saccharomyces cerevisiae. Reduced LCB2 expression rapidly decreases cellular fitness, yet increased expression has little effect. The wild-type expression level is therefore perched on the edge of a nonlinear fitness cliff. LCB2 is upregulated when cells are exposed to osmotic stress; consistent with this, the entire fitness curve is shifted upward to higher expression under osmotic stress, illustrating the selective force behind gene regulation. Expression levels of LCB2 are lower in wild yeast strains than in the experimental lab strain, suggesting that higher levels in the lab strain may be idiosyncratic. Reports indicate that the effect sizes of alleles contributing to variation in complex phenotypes differ among environments and genetic backgrounds; our results suggest that such differences may be explained as simple shifts in the position of nonlinear fitness curves.
ISSN:0737-4038
1537-1719
DOI:10.1093/molbev/mss248