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Fitness Effects of Cis-Regulatory Variants in the Saccharomyces cerevisiae TDH3 Promoter.

ABSTRACT: Variation in gene expression is widespread within and between species, but fitness consequences of this variation are generally unknown. Here, we use mutations in the Saccharomyces cerevisiae TDH3 promoter to assess how changes in TDH3 expression affect cell growth. From these data, we predict the fitness consequences of de novo mutations and natural polymorphisms in the TDH3 promoter. Nearly all mutations and polymorphisms in the TDH3 promoter were found to have no significant effect on fitness in the environment assayed, suggesting that the wild-type allele of this promoter is robust to the effects of most new cis-regulatory mutations.

SUBMITTER: Duveau F

PROVIDER: S-EPMC5850770 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Fitness Effects of Cis-Regulatory Variants in the Saccharomyces cerevisiae TDH3 Promoter.

Duveau Fabien F Toubiana William W Wittkopp Patricia J PJ

Molecular biology and evolution 20171101 11

Variation in gene expression is widespread within and between species, but fitness consequences of this variation are generally unknown. Here, we use mutations in the Saccharomyces cerevisiae TDH3 promoter to assess how changes in TDH3 expression affect cell growth. From these data, we predict the fitness consequences of de novo mutations and natural polymorphisms in the TDH3 promoter. Nearly all mutations and polymorphisms in the TDH3 promoter were found to have no significant effect on fitness ...[more]

PMID: 28961929

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Project description:Heritable variation in gene expression is common within species. Much of this variation is due to genetic differences outside of the gene with altered expression and is trans-acting. This trans-regulatory variation is often polygenic, with individual variants typically having small effects, making the genetic architecture and evolution of trans-regulatory variation challenging to study. Consequently, key questions about trans-regulatory variation remain, including the variability of trans-regulatory variation within a species, how selection affects trans-regulatory variation, and how trans-regulatory variants are distributed throughout the genome and within a species. To address these questions, we isolated and measured trans-regulatory differences affecting TDH3 promoter activity among 56 strains of Saccharomyces cerevisiae, finding that trans-regulatory backgrounds varied approximately twofold in their effects on TDH3 promoter activity. Comparing this variation to neutral models of trans-regulatory evolution based on empirical measures of mutational effects revealed that despite this variability in the effects of trans-regulatory backgrounds, stabilizing selection has constrained trans-regulatory differences within this species. Using a powerful quantitative trait locus mapping method, we identified ∼100 trans-acting expression quantitative trait locus in each of three crosses to a common reference strain, indicating that regulatory variation is more polygenic than previous studies have suggested. Loci altering expression were located throughout the genome, and many loci were strain specific. This distribution and prevalence of alleles is consistent with recent theories about the genetic architecture of complex traits. In all mapping experiments, the nonreference strain alleles increased and decreased TDH3 promoter activity with similar frequencies, suggesting that stabilizing selection maintained many trans-acting variants with opposing effects. This variation may provide the raw material for compensatory evolution and larger scale regulatory rewiring observed in developmental systems drift among species.

Project description:BackgroundSaccharomyces cerevisiae is widely studied for production of biofuels and biochemicals. To improve production efficiency under industrially relevant conditions, coordinated expression of multiple genes by manipulating promoter strengths is an efficient approach. It is known that gene expression is highly dependent on the practically used environmental conditions and is subject to dynamic changes. Therefore, investigating promoter activities of S. cerevisiae under different culture conditions in different time points, especially under stressful conditions is of great importance.ResultsIn this study, the activities of various promoters in S. cerevisiae under stressful conditions and in the presence of xylose were characterized using yeast enhanced green fluorescent protein (yEGFP) as a reporter. The stresses include toxic levels of acetic acid and furfural, and high temperature, which are related to fermentation of lignocellulosic hydrolysates. In addition to investigating eight native promoters, the synthetic hybrid promoter P3xC-TEF1 was also evaluated. The results revealed that P TDH3 and the synthetic promoter P3xC-TEF1 showed the highest strengths under almost all the conditions. Importantly, these two promoters also exhibited high stabilities throughout the cultivation. However, the strengths of P ADH1 and P PGK1 , which are generally regarded as 'constitutive' promoters, decreased significantly under certain conditions, suggesting that cautions should be taken to use such constitutive promoters to drive gene expression under stressful conditions. Interestingly, P HSP12 and P HSP26 were able to response to both high temperature and acetic acid stress. Moreover, P HSP12 also led to moderate yEGFP expression when xylose was used as the sole carbon source, indicating that this promoter could be used for inducing proper gene expression for xylose utilization.ConclusionThe results here revealed dynamic changes of promoter activities in S. cerevisiae throughout batch fermentation in the presence of inhibitors as well as using xylose. These results provide insights in selection of promoters to construct S. cerevisiae strains for efficient bioproduction under practical conditions. Our results also encouraged applications of synthetic promoters with high stability for yeast strain development.

Dataset Information

Fitness Effects of Cis-Regulatory Variants in the Saccharomyces cerevisiae TDH3 Promoter.

Publications

Fitness Effects of Cis-Regulatory Variants in the Saccharomyces cerevisiae TDH3 Promoter.

Similar Datasets

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