scholarly journals ADAPTIVE MUTAGENESIS IN THE YEAST SACCHAROMYCES CEREVISIAE

2006 ◽  
Vol 4 (3) ◽  
pp. 20-28 ◽  
Author(s):  
Nora Babudri ◽  
Angela Lucaccioni ◽  
Alessandro Achilli

The nature of mutation in microorganisms has been debated for a long time. Two theories have been at odds: random spontaneous mutagenesis vs. adaptive mutagenesis. "random mutagenesis" means that mutations occur in proliferating cells before they encountered the selective agent. "adaptive mutagenesis" means that advantageous mutations form in the environment where they have been selected, in non-replicating or poorly replicating cells even though other, non-selected, mutations occur at the same time. In the last 20 years it has been definitely shown that random as well as adaptive mutagenesis occur in bacteria and yeast. microorganisms in nature do not divide or divide poorly because of adverse environmental conditions; therefore adaptive mutations could provide cells with a selective advantage and allow evolution of populations. Here we will focus on some fundamental aspects of adaptive mutagenesis in the yeast Saccharomyces cerevisiae. We begin with a historical overview on the nature of mutation. We then focus on experimental systems aimed at proving or disproving adaptive mutagenesis. We have briefly summarized the results obtained in this field, with particular attention to genetic and molecular mechanisms.

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.


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.


2019 ◽  
Vol 20 (9) ◽  
pp. 2133 ◽  
Author(s):  
Antonella Locascio ◽  
Nuria Andrés-Colás ◽  
José Miguel Mulet ◽  
Lynne Yenush

Sodium and potassium are two alkali cations abundant in the biosphere. Potassium is essential for plants and its concentration must be maintained at approximately 150 mM in the plant cell cytoplasm including under circumstances where its concentration is much lower in soil. On the other hand, sodium must be extruded from the plant or accumulated either in the vacuole or in specific plant structures. Maintaining a high intracellular K+/Na+ ratio under adverse environmental conditions or in the presence of salt is essential to maintain cellular homeostasis and to avoid toxicity. The baker’s yeast, Saccharomyces cerevisiae, has been used to identify and characterize participants in potassium and sodium homeostasis in plants for many years. Its utility resides in the fact that the electric gradient across the membrane and the vacuoles is similar to plants. Most plant proteins can be expressed in yeast and are functional in this unicellular model system, which allows for productive structure-function studies for ion transporting proteins. Moreover, yeast can also be used as a high-throughput platform for the identification of genes that confer stress tolerance and for the study of protein–protein interactions. In this review, we summarize advances regarding potassium and sodium transport that have been discovered using the yeast model system, the state-of-the-art of the available techniques and the future directions and opportunities in this field.


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>


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.


Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 400 ◽  
Author(s):  
Christian Oporto ◽  
Carlos Villarroel ◽  
Sebastián Tapia ◽  
Verónica García ◽  
Francisco Cubillos

Patulin (4-hydroxy-4H-furo[3,2c]pyran-2[6H]-one) is a mycotoxin produced by a suite of fungi species. Patulin is toxic to humans and is a sporadic contaminant in products that were made from fungi-infected fruits. The baker yeast Saccharomyces cerevisiae (S. cerevisiae) has been shown to decrease patulin levels likely by converting it to the less harmful E-ascladiol, yet this capacity is dependent on the strain utilized. In this study we show that four representative strains of different S. cerevisiae lineages differ in their ability to tolerate and decrease patulin levels in solution, demonstrating that some strains are better suitable for patulin biocontrol. Indeed, we tested the biocontrol capacities of the best patulin-reducer strain (WE) in contaminated apple juice and demonstrated their potential role as an efficient natural biocontrol solution. To investigate the mechanisms behind the differences between strains, we explored transcriptomic changes of the top (WE strain) and worst (WA strain) patulin-biocontroller strains after being exposed to this toxin. Large and significant gene expression differences were found between these two strains, the majority of which represented genes associated with protein biosynthesis, cell wall composition and redox homeostasis. Interestingly, the WE isolate exhibited an overrepresentation of up-regulated genes involved in membrane components, suggesting an active role of the membrane towards patulin detoxification. In contrast, WA upregulated genes were associated with RNA metabolism and ribosome biogenesis, suggesting a patulin impact upon transcription and translation activity. These results suggest that different genotypes of S. cerevisiae encounter different stresses from patulin toxicity and that different rates of detoxification of this toxin might be related with the plasma membrane composition. Altogether, our data demonstrates the different molecular mechanisms in S. cerevisiae strains withstanding patulin exposure and opens new avenues for the selection of new patulin biocontroller strains.


2011 ◽  
Vol 10 (10) ◽  
pp. 1367-1369 ◽  
Author(s):  
Shigeyuki Kawai ◽  
Jörg Urban ◽  
Manuele Piccolis ◽  
Nicolas Panchaud ◽  
Claudio De Virgilio ◽  
...  

ABSTRACTTORC1-dependent phosphorylation ofSaccharomyces cerevisiaeSch9 was dramatically reduced upon exposure to a protonophore or in respiration-incompetent ρ0cells but not in respiration-incompetentpetmutants, providing important insight into the molecular mechanisms governing interorganellar signaling in general and retrograde signaling in particular.


Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 9-21 ◽  
Author(s):  
D F Steele ◽  
S Jinks-Robertson

Abstract Reversion to Lys+ prototrophy in a haploid yeast strain containing a defined lys2 frameshift mutation has been examined. When cells were plated on synthetic complete medium lacking only lysine, the numbers of Lys+ revertant colonies accumulated in a time-dependent manner in the absence of any detectable increase in cell number. An examination of the distribution of the numbers of early appearing Lys+ colonies from independent cultures suggests that the mutations to prototrophy occurred randomly during nonselective growth. In contrast, an examination of the distribution of late appearing Lys+ colonies indicates that the underlying reversion events occurred after selective plating. No accumulation of Lys+ revertants occurred when cells were starved for tryptophan, leucine or both lysine and tryptophan prior to plating selectively for Lys+ revertants. These results indicate that mutations accumulate more frequently when they confer a selective advantage, and are thus consistent with the occurrence of adaptive mutations in yeast.


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