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Mol Biol Evol. 2013 Feb;30(2):448-56. doi: 10.1093/molbev/mss248. Epub 2012 Oct 27.

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

Author information

1
Department of Ecology and Evolution, Stony Brook University, USA. joshua.rest@stonybrook.edu

Abstract

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.

PMID:
23104081
PMCID:
PMC3548308
DOI:
10.1093/molbev/mss248
[Indexed for MEDLINE]
Free PMC Article

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