scholarly journals The Role of Ancestral Duplicated Genes in Adaptation to Growth on Lactate, a Non-Fermentable Carbon Source for the Yeast Saccharomyces cerevisiae

2021 ◽  
Vol 22 (22) ◽  
pp. 12293
Author(s):  
Florian Mattenberger ◽  
Mario A. Fares ◽  
Christina Toft ◽  
Beatriz Sabater-Muñoz

The cell central metabolism has been shaped throughout evolutionary times when facing challenges from the availability of resources. In the budding yeast, Saccharomyces cerevisiae, a set of duplicated genes originating from an ancestral whole-genome and several coetaneous small-scale duplication events drive energy transfer through glucose metabolism as the main carbon source either by fermentation or respiration. These duplicates (~a third of the genome) have been dated back to approximately 100 MY, allowing for enough evolutionary time to diverge in both sequence and function. Gene duplication has been proposed as a molecular mechanism of biological innovation, maintaining balance between mutational robustness and evolvability of the system. However, some questions concerning the molecular mechanisms behind duplicated genes transcriptional plasticity and functional divergence remain unresolved. In this work we challenged S. cerevisiae to the use of lactic acid/lactate as the sole carbon source and performed a small adaptive laboratory evolution to this non-fermentative carbon source, determining phenotypic and transcriptomic changes. We observed growth adaptation to acidic stress, by reduction of growth rate and increase in biomass production, while the transcriptomic response was mainly driven by repression of the whole-genome duplicates, those implied in glycolysis and overexpression of ROS response. The contribution of several duplicated pairs to this carbon source switch and acidic stress is also discussed.

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Beatriz Sabater-Muñoz ◽  
Florian Mattenberger ◽  
Mario A. Fares ◽  
Christina Toft

ABSTRACT Ethanol is the main by-product of yeast sugar fermentation that affects microbial growth parameters, being considered a dual molecule, a nutrient and a stressor. Previous works demonstrated that the budding yeast arose after an ancient hybridization process resulted in a tier of duplicated genes within its genome, many of them with implications in this ethanol “produce-accumulate-consume” strategy. The evolutionary link between ethanol production, consumption, and tolerance versus ploidy and stability of the hybrids is an ongoing debatable issue. The implication of ancestral duplicates in this metabolic rewiring, and how these duplicates differ transcriptionally, remains unsolved. Here, we study the transcriptomic adaptive signatures to ethanol as a nonfermentative carbon source to sustain clonal yeast growth by experimental evolution, emphasizing the role of duplicated genes in the adaptive process. As expected, ethanol was able to sustain growth but at a lower rate than glucose. Our results demonstrate that in asexual populations a complete transcriptomic rewiring was produced, strikingly by downregulation of duplicated genes, mainly whole-genome duplicates, whereas small-scale duplicates exhibited significant transcriptional divergence between copies. Overall, this study contributes to the understanding of evolution after gene duplication, linking transcriptional divergence with duplicates’ fate in a multigene trait as ethanol tolerance. IMPORTANCE Gene duplication events have been related with increasing biological complexity through the tree of life, but also with illnesses, including cancer. Early evolutionary theories indicated that duplicated genes could explore alternative functions due to relaxation of selective constraints in one of the copies, as the other remains as ancestral-function backup. In unicellular eukaryotes like yeasts, it has been demonstrated that the fate and persistence of duplicates depend on duplication mechanism (whole-genome or small-scale events), shaping their actual genomes. Although it has been shown that small-scale duplicates tend to innovate and whole-genome duplicates specialize in ancestral functions, the implication of duplicates’ transcriptional plasticity and transcriptional divergence on environmental and metabolic responses remains largely obscure. Here, by experimental adaptive evolution, we show that Saccharomyces cerevisiae is able to respond to metabolic stress (ethanol as nonfermentative carbon source) due to the persistence of duplicated genes. These duplicates respond by transcriptional rewiring, depending on their transcriptional background. Our results shed light on the mechanisms that determine the role of duplicates, and on their evolvability.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Peter Higgins ◽  
Cooper A Grace ◽  
Soon A Lee ◽  
Matthew R Goddard

Abstract Saccharomyces cerevisiae is extensively utilized for commercial fermentation, and is also an important biological model; however, its ecology has only recently begun to be understood. Through the use of whole-genome sequencing, the species has been characterized into a number of distinct subpopulations, defined by geographical ranges and industrial uses. Here, the whole-genome sequences of 104 New Zealand (NZ) S. cerevisiae strains, including 52 novel genomes, are analyzed alongside 450 published sequences derived from various global locations. The impact of S. cerevisiae novel range expansion into NZ was investigated and these analyses reveal the positioning of NZ strains as a subgroup to the predominantly European/wine clade. A number of genomic differences with the European group correlate with range expansion into NZ, including 18 highly enriched single-nucleotide polymorphism (SNPs) and novel Ty1/2 insertions. While it is not possible to categorically determine if any genetic differences are due to stochastic process or the operations of natural selection, we suggest that the observation of NZ-specific copy number increases of four sugar transporter genes in the HXT family may reasonably represent an adaptation in the NZ S. cerevisiae subpopulation, and this correlates with the observations of copy number changes during adaptation in small-scale experimental evolution studies.


1989 ◽  
Vol 9 (2) ◽  
pp. 442-451
Author(s):  
M Nishizawa ◽  
R Araki ◽  
Y Teranishi

To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UASPYK1) located between 634 and 653 nucleotides upstream of the initiating ATG codon. The promoter activity of the PYK 5'-noncoding region was abolished when the sequence containing the UASPYK1 was deleted from the region. Synthetic UASPYK1 (26mer), in either orientation, was able to restore the transcriptional activity of UAS-depleted mutants when placed upstream of the TATA sequence located at -199 (ATG as +1). While the UASPYK1 was required for basal to intermediate levels of transcriptional activation, a sequence between -714 and -811 was found to be necessary for full activation. On the other hand, a sequence between -344 and -468 was found to be responsible for transcriptional repression of the PYK gene when yeast cells were grown on nonfermentable carbon sources. This upstream repressible sequence also repressed transcription, although to a lesser extent, when glucose was present in the medium. The possible mechanism for carbon source-dependent regulation of PYK expression through these cis-acting regulatory elements is discussed.


1978 ◽  
Vol 24 (6) ◽  
pp. 637-642 ◽  
Author(s):  
K. C. Thomas ◽  
Mary Spencer

Effects of the carbon source and oxygen on ethylene production by the yeast Saccharomyces cerevisiae have been studied. The amounts of ethylene evolved by the yeast culture were less than those detected in the blank (an equal volume of uninoculated medium), suggesting a net absorption of ethylene by the yeast cells. Addition of glucose to the lactate-grown yeast culture induced ethylene production. This glucose-induced stimulation of ethylene production was inhibited to a great extent by cycloheximide. Results suggested that the yeast cells in the presence of glucose synthesized an ethylene precursor and passed it into the medium. The conversion of this precursor to ethylene might be stimulated by oxygen. The fact that ethylene was produced by the yeast growing anaerobically and also by respiration-deficient mutants isolated from the wild-type yeast suggested that mitochondrial ATP synthesis was not an absolute requirement for ethylene biogenesis.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3359
Author(s):  
Dimitris Liakopoulos

In the yeast Saccharomyces cerevisiae DNA replication and spindle assembly can overlap. Therefore, signaling mechanisms modulate spindle dynamics in order to ensure correct timing of chromosome segregation relative to genome duplication, especially when replication is incomplete or the DNA becomes damaged. This review focuses on the molecular mechanisms that coordinate DNA replication and spindle dynamics, as well as on the role of spindle-dependent forces in DNA repair. Understanding the coupling between genome duplication and spindle function in yeast cells can provide important insights into similar processes operating in other eukaryotic organisms, including humans.


1995 ◽  
Vol 15 (4) ◽  
pp. 1915-1922 ◽  
Author(s):  
D Hedges ◽  
M Proft ◽  
K D Entian

The expression of gluconeogenic fructose-1,6-bisphosphatase (encoded by the FBP1 gene) depends on the carbon source. Analysis of the FBP1 promoter revealed two upstream activating elements, UAS1FBP1 and UAS2FBP1, which confer carbon source-dependent regulation on a heterologous reporter gene. On glucose media neither element was activated, whereas after transfer to ethanol a 100-fold derepression was observed. This gene activation depended on the previously identified derepression genes CAT1 (SNF1) (encoding a protein kinase) and CAT3 (SNF4) (probably encoding a subunit of Cat1p [Snf1p]). Screening for mutations specifically involved in UAS1FBP1 derepression revealed the new recessive derepression mutation cat8. The cat8 mutants also failed to derepress UAS2FBP1, and these mutants were unable to grow on nonfermentable carbon sources. The CAT8 gene encodes a zinc cluster protein related to Saccharomyces cerevisiae Gal4p. Deletion of CAT8 caused a defect in glucose derepression which affected all key gluconeogenic enzymes. Derepression of glucose-repressible invertase and maltase was still normally regulated. A CAT8-lacZ promoter fusion revealed that the CAT8 gene itself is repressed by Cat4p (Mig1p). These results suggest that gluconeogenic genes are derepressed upon binding of Cat8p, whose synthesis depends on the release of Cat4p (Mig1p) from the CAT8 promoter. However, gluconeogenic promoters are still glucose repressed in cat4 mutants, which indicates that in addition to its transcription, the Cat8p protein needs further activation. The observation that multicopy expression of CAT8 reverses the inability of cat1 and cat3 mutants to grow on ethanol indicates that Cat8p might be the substrate of the Cat1p/Cat3p protein kinase.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi271-vi271
Author(s):  
Sophie Fiola ◽  
Eli Ganni ◽  
Rita Lo ◽  
Ka Yee Lok ◽  
Elena Kuzmin ◽  
...  

Abstract High levels of D-2-hydroxyglutarate (D2HG) are found in several types of cancers, most notably low grade gliomas (LGGs). The accumulation of D-2HG contributes to tumorigenesis through a variety of mechanisms including decreased utilization of oxidative phosphorylation and histone hypermethylation. The use of the budding yeast Saccharomyces cerevisiae as a model system to study cancer allows for faster, more efficient elucidation of various molecular mechanisms, including functional genomics via genomic array screening. S. cerevisiae encodes two homologs of the human D-2HG dehydrogenase: the mitochondrial Dld2 and cytosolic Dld3. We detected an increase in the production of D-2HG in the dld3∆ knockout strain by LC-MS. In addition, the dld3∆ knockout strain shows decreased survival and a growth impairment in glucose-containing liquid media. However, this strain did not show a significant growth impairment on glucose or glycerol-containing solid media. Using publicly available Synthetic Genomic Array (SGA) analysis data from TheCellMap.org, we investigated the top negative gene interactions for our dld3 knockout strain. GO analysis of these negative gene interactions showed enrichment of targets locating to the mitochondria, suggesting that the increase of 2-HG leads to mitochondrial impairment, consistent with previous observations in other models of LGGs. The top two targets of the SGA screen were mdm35, a mitochondrial interspace membrane protein involved in assembly of the mitochondrial respiratory chain complex and cdc8, a component of the de novo pyrimidine biosynthesis pathway. Taken together, these results suggest that the dld3∆ knockout strain is an appropriate model in which to study the D-2HG-driven changes that occur during tumorigenesis.


PLoS Genetics ◽  
2013 ◽  
Vol 9 (1) ◽  
pp. e1003176 ◽  
Author(s):  
Mario A. Fares ◽  
Orla M. Keane ◽  
Christina Toft ◽  
Lorenzo Carretero-Paulet ◽  
Gary W. Jones

2015 ◽  
Vol 65 (6) ◽  
pp. 444
Author(s):  
Ramesh C. Meena ◽  
Amitabha Chakrabarti

<p>The versatility of the yeast experimental model has aided in innumerable ways in the understanding of fundamental cellular functions and has also contributed towards the elucidation of molecular mechanisms underlying several pathological conditions in humans. Genome-wide expression, functional, localization and interaction studies on the yeast Saccharomyces cerevisiae exposed to various stressors have made profound contributions towards the understanding of stress response pathways. Analysis of gene expression data from S. cerevisiae cells indicate that the expression of a common set of genes is altered upon exposure to all the stress conditions examined. This common response to multiple stressors is known as the Environmental stress response. Knowledge gained from studies on the yeast model has now become helpful in understanding stress response pathways and associated disease conditions in humans. Cross-species microarray experiments and analysis of data with ever improving computational methods has led to a better comparison of gene expression data between diverse organisms that include yeast and humans.</p>


1983 ◽  
Vol 29 (9) ◽  
pp. 1200-1204 ◽  
Author(s):  
E. Valdivia ◽  
J. Martinez ◽  
J. M. Ortega ◽  
E. Montoya

The effect of carbon source and oxygen tension on catalase and peroxidase levels and on the intermediates of the biosynthesis of the prosthetic group of both enzymes has been studied. Oxygen produces an increase of both enzymatic activities, even in presence of glucose. On the other hand it seems probable that glucose does not have a direct inhibitory effect on the biosynthesis of 5-aminolevulinic acid (ALA) and porphyrins.


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