Polymorphisms in the yeast galactose sensor underlie a natural continuum of nutrient-decision phenotypes

Lee, Kayla; Wang, Jue; Palme, Julius; Escalante-Chong, Renan; Hua, Bo; Springer, Michael

doi:10.1371/journal.pgen.1006766

Cited by 20 publications

(41 citation statements)

References 95 publications

(170 reference statements)

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“…A previous study identified GAL3 as an important genetic determinant for this decision: The concentration ratio at which cells turn GAL expression ON differs between strains harboring different natural alleles of GAL3 (Lee et al , ). We asked if this variation, visible in the steady‐state exposure to both glucose and galactose, was correlated with the variation observed on the dynamics of network induction upon exposure to galactose only.…”

Section: Resultsmentioning

confidence: 99%

“…We asked if this variation, visible in the steady‐state exposure to both glucose and galactose, was correlated with the variation observed on the dynamics of network induction upon exposure to galactose only. We chose four strains that showed different decision thresholds because of different GAL3 alleles (Lee et al , ; Fig B), and we monitored their dynamics of induction at three different concentrations of galactose (with no glucose). We then used our model to assign ρ Gal3 and K Gal parameter values to each strain.…”

Section: Resultsmentioning

confidence: 99%

“…Genotype was validated by PCR and sequencing. Strains of Fig were MPJ125‐E06 ( GAL3 BY ), MPJ143‐H01 ( GAL3 YJM428 ), MPJ143‐F01 ( GAL3 YJM421 ), and MPJ125‐A07 ( GAL3 BC187 ), which were described in another study (Lee et al , ); they all derived from a S288c hoΔ::GAL1pr‐YFP‐mTagBFP2‐kanMX4; gal3∆::hphNT1 parental strain. Strains GY2180 and GY2181 carrying mutations GAL3 W117A and GAL3 W117T , respectively, were obtained using CRISPR/Cas9: Oligonucleotides 1P29 and 1P30 were annealed and cloned in the SwaI, BclI sites of the pML104 plasmid (Laughery et al , ) to produce pGY514.…”

Section: Methodsmentioning

confidence: 99%

“…Expression of GAL3 is itself under Gal4p/Gal80p control (positive feedback). In addition, the sequence of GAL3 differs between natural isolates of S. cerevisiae and this allelic variation was recently associated with different sensitivities of the network to galactose (Lee et al , ). There are multiple ways that a GAL3 variant could affect the dynamics of induction: by modifying the production or degradation rates of the Gal3p protein or of its messenger RNA, by changing the affinity of Gal3p to galactose or ATP, by changing the capacity of Gal3p to dimerize, by changing the nucleocytoplasmic ratio of Gal3p molecules, or by changing the affinity of Gal3p to Gal80p.…”

Section: Introductionmentioning

confidence: 99%

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Assigning function to natural allelic variation via dynamic modeling of gene network induction

Richard

Chuffart

Duplus-Bottin

et al. 2018

Molecular Systems Biology

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More and more natural DNA variants are being linked to physiological traits. Yet, understanding what differences they make on molecular regulations remains challenging. Important properties of gene regulatory networks can be captured by computational models. If model parameters can be “personalized” according to the genotype, their variation may then reveal how DNA variants operate in the network. Here, we combined experiments and computations to visualize natural alleles of the yeast GAL3 gene in a space of model parameters describing the galactose response network. Alleles altering the activation of Gal3p by galactose were discriminated from those affecting its activity (production/degradation or efficiency of the activated protein). The approach allowed us to correctly predict that a non‐synonymous SNP would change the binding affinity of Gal3p with the Gal80p transcriptional repressor. Our results illustrate how personalizing gene regulatory models can be used for the mechanistic interpretation of genetic variants.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assigning function to natural allelic variation via dynamic modeling of gene network induction

Richard

Chuffart

Duplus-Bottin

et al. 2018

Molecular Systems Biology

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“…This Gal1-mCherry expression correlated with a fitness benefit in 0.2% glucose + 1.8% galactose medium. In this medium, once glucose is exhausted after ~7h of growth, naïve cells exhibited a significant lag before adapting to galactose (Figure 1G; refs 27, 29, 30). However, during memory or in the presence of ectopic Gal1, this lag was absent and cells adapted immediately to galactose (Figure 1G).…”

Section: Resultsmentioning

confidence: 99%

Genetic and Epigenetic Strategies Potentiate Gal4 Activation to Enhance Fitness in Recently Diverged Yeast Species

Sood

Brickner

2017

Current Biology

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Summary Certain genes show rapid reactivation after several generations of repression, a conserved phenomenon called epigenetic transcriptional memory. Following previous growth in galactose, GAL gene transcriptional memory confers a strong fitness benefit in Saccharomyces cerevisiae adapting to growth in galactose for up to 8 generations. A genetic screen for mutants defective for GAL gene memory revealed new insights into the molecular mechanism, adaptive consequences and evolutionary history of memory. A point mutation in the Gal1 coactivator that disrupts the interaction with the Gal80 inhibitor specifically and completely disrupted memory. This mutation confirms that cytoplasmically-inherited Gal1 produced during previous growth in galactose directly interferes with Gal80 repression to promote faster induction of GAL genes. This mitotically heritable mode of regulation is recently evolved; in a diverged Saccharomyces species, GAL genes show constitutively faster activation due to genetically-encoded basal expression of Gal1. Thus, recently diverged species utilize either epigenetic or genetic strategies to regulate the same molecular mechanism. The screen also revealed that the central domain of the Gal4 transcription factor both regulates the stochasticity of GAL gene expression and potentiates stronger GAL gene activation in the presence of Gal1. The central domain is critical for GAL gene transcriptional memory; Gal4 lacking the central domain fails to potentiate GAL gene expression and is unresponsive to previous Gal1 expression.

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Long-Term Adaptation to Galactose as a Sole Carbon Source Selects for Mutations Outside the Canonical GAL Pathway

et al. 2022

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Galactose is a secondary fermentable sugar that requires specific regulatory and structural genes for its assimilation, which are under catabolite repression by glucose. When glucose is absent, the catabolic repression is attenuated, and the structural GAL genes are fully activated. In Saccharomyces cerevisiae , the GAL pathway is under selection in environments where galactose is present. However, it is unclear the adaptive strategies in response to long-term propagation in galactose as a sole carbon source in laboratory evolution experiments. Here, we performed a 4,000-generation evolution experiment using 48 diploid Saccharomyces cerevisiae populations to study adaptation in galactose. We show that fitness gains were greater in the galactose-evolved population than in identically evolved populations with glucose as a sole carbon source. Whole-genome sequencing of 96 evolved clones revealed recurrent de novo single nucleotide mutations in candidate targets of selection, copy number variations, and ploidy changes. We find that most mutations that improve fitness in galactose lie outside of the canonical GAL pathway. Reconstruction of specific evolved alleles in candidate target of selection, SEC23 and IRA1 , showed a significant increase in fitness in galactose compared to glucose. In addition, most of our evolved populations (28/46; 61%) fixed aneuploidies on Chromosome VIII, suggesting a parallel adaptive amplification. Finally, we show greater loss of extrachromosomal elements in our glucose-evolved lineages compared with previous glucose evolution. Broadly, these data further our understanding of the evolutionary pressures that drive adaptation to less-preferred carbon sources. Supplementary Information The online version contains supplementary material available at 10.1007/s00239-022-10079-9.

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Polymorphisms in the yeast galactose sensor underlie a natural continuum of nutrient-decision phenotypes

Cited by 20 publications

References 95 publications

Assigning function to natural allelic variation via dynamic modeling of gene network induction

Assigning function to natural allelic variation via dynamic modeling of gene network induction

Genetic and Epigenetic Strategies Potentiate Gal4 Activation to Enhance Fitness in Recently Diverged Yeast Species

Long-Term Adaptation to Galactose as a Sole Carbon Source Selects for Mutations Outside the Canonical GAL Pathway

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