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Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.

ABSTRACT: Genetic networks are surprisingly robust to perturbations caused by new mutations. This robustness is conferred in part by compensation for loss of a gene's activity by genes with overlapping functions, such as paralogs. Compensation occurs passively when the normal activity of one paralog can compensate for the loss of the other, or actively when a change in one paralog's expression, localization, or activity is required to compensate for loss of the other. The mechanisms of active compensation remain poorly understood in most cases. Here we investigate active compensation for the loss or reduction in expression of the Saccharomyces cerevisiae gene TDH3 by its paralog TDH2. TDH2 is upregulated in a dose-dependent manner in response to reductions in TDH3 by a mechanism requiring the shared transcriptional regulators Gcr1p and Rap1p. TDH1, a second and more distantly related paralog of TDH3, has diverged in its regulation and is upregulated by another mechanism. Other glycolytic genes regulated by Rap1p and Gcr1p show changes in expression similar to TDH2, suggesting that the active compensation by TDH3 paralogs is part of a broader homeostatic response mediated by shared transcriptional regulators.

SUBMITTER: Vande Zande P

PROVIDER: S-EPMC10752532 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.

Vande Zande Pétra P Siddiq Mohammad A MA Hodgins-Davis Andrea A Kim Lisa L Wittkopp Patricia J PJ

PLoS genetics 20231213 12

Genetic networks are surprisingly robust to perturbations caused by new mutations. This robustness is conferred in part by compensation for loss of a gene's activity by genes with overlapping functions, such as paralogs. Compensation occurs passively when the normal activity of one paralog can compensate for the loss of the other, or actively when a change in one paralog's expression, localization, or activity is required to compensate for loss of the other. The mechanisms of active compensation ...[more]

PMID: 38091349

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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.

Dataset Information

Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.

Publications

Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.

Similar Datasets

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