scholarly journals Hsf1 phosphorylation generates cell-to-cell variation in Hsp90 levels and promotes phenotypic plasticity

2017 ◽  
Author(s):  
Xu Zheng ◽  
Ali Beyzavi ◽  
Joanna Krakowiak ◽  
Nikit Patel ◽  
Ahmad S. Khalil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phenotypic Plasticity ◽  
Important Determinant ◽  
Phenotypic Diversity ◽  
Yeast Cells ◽  
Wide Range ◽  
Differential Tuning ◽  
Gene Expression Heterogeneity ◽  
Noise In Gene Expression ◽  
Cell Variation

ABSTRACTClonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this “noise” in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock transcription factor (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90 – a known “phenotypic capacitor” and canonical Hsf1 target. We show that Hsf1 phosphorylation promotes cell-to-cell variation, and this variation – rather than absolute Hsf1 activity – promotes antifungal resistance. We propose that Hsf1 phosphorylation enables differential tuning of the proteostasis network in individual cells, allowing populations to access a wide range of phenotypic states.

scholarly journals Empirical noise-mean fitness landscapes and the evolution of gene expression

2018 ◽  
Author(s):  
Joern M Schmiedel ◽  
Lucas B. Carey ◽  
Ben Lehner
Keyword(s):  
Gene Expression ◽  
Fitness Landscape ◽  
Fitness Landscapes ◽  
Similar Magnitude ◽  
Expression Systems ◽  
Fitness Effects ◽  
Mean Fitness ◽  
Noise In Gene Expression ◽  
Cell Variation ◽  
Magnitude Sensitivity

The effects of cell-to-cell variation (noise) in gene expression have proven difficult to quantify, in part due to the mechanistic coupling of noise to mean expression. To independently evaluate the effects of changes in expression mean and noise we determined the fitness landscapes in mean-noise expression space for 33 genes in yeast. The landscapes can be decomposed into two principal topologies: the fitness effects of protein shortage and surplus. For most genes, the fitness impact of sustained (mean) and short-lived (noise) deviations away from the expression optimum are linked and of similar magnitude. Sensitivity to both protein shortage and surplus creates a fitness landscape in which an epistatic ratchet uncouples the evolution of noise from mean expression, promoting noise minimization. These results demonstrate that noise is detrimental for many genes and reveal non-trivial consequences of mean-noise-fitness topologies for the evolution of gene expression systems.

scholarly journals The role of epigenetic regulation in adaptive phenotypic plasticity of plants

2021 ◽  
Vol 78 (5) ◽  
pp. 347-359
Author(s):  
E.L. Kordyum ◽  
◽  
D.V. Dubyna ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Phenotypic Plasticity ◽  
Epigenetic Regulation ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Model Species ◽  
Wide Range ◽  
Adaptive Phenotypic Plasticity

In recent decades, knowledge about the role of epigenetic regulation of gene expression in plant responses to external stimuli and in adaptation of plants to adverse environmental fluctuations have extended significantly. DNA methylation is considered as the main molecular mechanism that provides genomic information and contributes to the understanding of the molecular basis of phenotypic variations based on epigenetic modifications. Unfortunately, the vast majority of research in this area has been performed on the model species Arabidopsis thaliana. The development of the methylation-sensitive amplified polymorphism (MSAP) method has made it possible to implement the large-scale detection of DNA methylation alterations in wild non-model and agricultural plants with large and highly repetitive genomes in natural and manipulated habitats. The article presents current information on DNA methylation in species of natural communities and crops and its importance in plant development and adaptive phenotypic plasticity, along with brief reviews of current ideas about adaptive phenotypic plasticity and epigenetic regulation of gene expression. The great potential of further studies of the epigenetic role in phenotypic plasticity of a wide range of non-model species in natural populations and agrocenoses for understanding the molecular mechanisms of plant existence in the changing environment in onto- and phylogeny, directly related to the key tasks of forecasting the effects of global warming and crop selection, is emphasized. Specific taxa of the Ukrainian flora, which, in authors’ opinion, are promising and interesting for this type of research, are recommended.

scholarly journals Adaptive tuning of cell sensory diversity without changes in gene expression

2020 ◽  
Vol 6 (46) ◽  
pp. eabc1087
Author(s):  
K. Kamino ◽  
J. M. Keegstra ◽  
J. Long ◽  
T. Emonet ◽  
T. S. Shimizu
Keyword(s):  
Gene Expression ◽  
Posttranslational Modifications ◽  
Phenotypic Diversity ◽  
Covalent Modification ◽  
Environmental Cues ◽  
Bet Hedging ◽  
Allosteric Coupling ◽  
The Face ◽  
Survival And Growth ◽  
Cell Variation

In the face of uncertainty, cell populations tend to diversify to enhance survival and growth. Previous studies established that cells can optimize such bet hedging upon environmental change by modulating gene expression to adapt both the average and diversity of phenotypes. Here, we demonstrate that cells can tune phenotypic diversity also using posttranslational modifications. In the chemotaxis network of Escherichia coli, we find, for both major chemoreceptors Tar and Tsr, that cell-to-cell variation in response sensitivity is dynamically modulated depending on the presence or absence of their cognate chemoeffector ligands in the environment. Combining experiments with mathematical modeling, we show that this diversity tuning requires only the environment-dependent covalent modification of chemoreceptors and a standing cell-to-cell variation in their allosteric coupling. Thus, when environmental cues are unavailable, phenotypic diversity enhances the population’s readiness for many signals. However, once a signal is perceived, the population focuses on tracking that signal.

scholarly journals Diagnostic assessments of student thinking about stochastic processes

2016 ◽  
Author(s):  
Michael W. Klymkowsky ◽  
Katja Koehler ◽  
Melanie M. Cooper
Keyword(s):  
Gene Expression ◽  
Stochastic Processes ◽  
Open Source ◽  
Biological Systems ◽  
Student Understanding ◽  
Student Thinking ◽  
Death Rates ◽  
Formal Instruction ◽  
Wide Range ◽  
Noise In Gene Expression

AbstractA number of research studies indicate that students often have difficulties in understanding the presence and/or the implications of stochastic processes within biological systems. While critical to a wide range of phenomena, the presence and implications of stochastic processes are rarely explicitly considered in the course of formal instruction. To help instructors identify gaps in student understanding, we have designed and tested six open source activities covering a range of scenarios, from death rates to noise in gene expression, that can be employed, alone or in combination, as diagnostics to reveal student thinking as a prelude to the presentation of stochastic processes within a course or a curriculum.

scholarly journals Thickening of the cell wall increases the resistance of S. cerevisiae to commercial formulations of glyphosate

2019 ◽  
Author(s):  
Apoorva Ravishankar ◽  
Amaury Pupo ◽  
Jennifer E.G. Gallagher
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Adverse Effects ◽  
Mapk Signaling ◽  
Fragile Sites ◽  
Yeast Cells ◽  
Global Changes ◽  
Wide Range ◽  
A Cell

AbstractThe use of glyphosate-based herbicides is widespread and despite its extensive use, its effects are yet to be deciphered completely. The additives in commercial formulations of glyphosate, though labeled as inert when used individually, have adverse effects when used in combination with other additives and the active ingredient. As a species, Saccharomyces cerevisiae has a wide range of resistance to glyphosate-based herbicides. To investigate the underlying genetic differences between sensitive and resistant strains, global changes in gene expression were measured when yeast were exposed to a commercial formulation of glyphosate (CFG). Changes in gene expression involved in numerous pathways such as DNA replication, MAPK signaling, meiosis, and cell wall synthesis. Because so many diverse pathways were affected, these strains were then subjected to in-lab-evolutions (ILE) to select mutations that confer increased resistance. Common fragile sites were found to play a role in adaptation mechanisms used by cells to attain resistance with long-term exposure to CFG. The cell wall structure acts as a protective barrier in alleviating the stress caused by exposure to CFG. The thicker the cell wall, the more resistant the cell is against CFG. Hence, a detailed study of the changes occurring at the genome and transcriptome level is essential to better understand the possible effects of CFG on the cell as a whole.Author SummaryWe are exposed to various chemicals in the environment on a daily basis. Some of these chemicals are herbicides that come in direct contact with the food we consume. This makes the thorough investigation of these chemicals crucial. Some of the most commonly used herbicides around the world are glyphosate-based. Their mode of action effects a biosynthetic pathway that is absent in mammals and insects and so it is deemed safe for consumption. However, there are many additives to these herbicides that increase its effects. Thorough testing of these commercially available herbicides is essential to decipher all the potentially adverse effects that it could have on a cell. Saccharomyces cerevisiae has a wide range of genetic diversity, making it is suitable to test different chemicals and identify any harmful effects. In this study, we exposed yeast cells to some glyphosate-based herbicides available in the market, to understand what effects it could have on a cell. We found that the additives in the herbicides have an effect on the cell wall and the mode of entry of glyphosate into the cell.

scholarly journals Adaptive noise

2013 ◽  
Vol 280 (1767) ◽  
pp. 20131104 ◽  
Author(s):  
Mark Viney ◽  
Sarah E. Reece
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Phenotypic Diversity ◽  
Biological Systems ◽  
Bet Hedging ◽  
Hedging Strategy ◽  
Phenotypic Differences ◽  
Fitness Benefits ◽  
Adaptive Noise ◽  
Noise In Gene Expression

In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.

scholarly journals Single-cell phenotyping and RNA sequencing reveal novel patterns of gene expression heterogeneity and regulation during growth and stress adaptation in a unicellular eukaryote

2018 ◽  
Author(s):  
Malika Saint ◽  
François Bertaux ◽  
Wenhao Tang ◽  
Xi-Ming Sun ◽  
Laurence Game ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Size ◽  
Single Cells ◽  
Yeast Cells ◽  
Stress Adaptation ◽  
Unicellular Eukaryote ◽  
Gene Expression Heterogeneity ◽  
Cell To Cell Variability

Cell-to-cell variability is central for microbial populations and contributes to cell function, stress adaptation and drug resistance. Gene-expression heterogeneity underpins this variability, but has been challenging to study genome-wide. Here, we report an integrated approach for imaging of individual fission yeast cells followed by single-cell RNA sequencing (scRNA-seq) and novel Bayesian normalisation. We analyse >2000 single cells and >700 matching RNA controls in various environmental conditions and identify sets of highly variable genes. Combining scRNA-seq with cell-size measurements provides unique insights into genes regulated during cell growth and division in single cells, including genes whose expression does not scale with cell size. We further analyse the heterogeneity and dynamics of gene expression during adaptive and acute responses to changing environments. Entry into stationary phase is preceded by a gradual, synchronised adaptation in gene regulation, followed by highly variable gene expression when growth decreases. Conversely, a sudden and acute heat-shock leads to a stronger and coordinated response and adaptation across cells. This analysis reveals that the extent and dynamics of global gene-expression heterogeneity is regulated in response to different physiological conditions within populations of a unicellular eukaryote. In summary, this works illustrates the potential of combined transcriptomics and imaging analysis in single cells to provide comprehensive and unbiased mechanistic understanding of cell-to-cell variability in microbial communities.

Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil

2019 ◽  
Vol 19 (5) ◽  
pp. 599-609 ◽  
Author(s):  
Sumathi Sundaravadivelu ◽  
Sonia K. Raj ◽  
Banupriya S. Kumar ◽  
Poornima Arumugamand ◽  
Padma P. Ragunathan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Death ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Normal Cells ◽  
Black Cumin ◽  
In Silico Docking ◽  
Wide Range

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.

Phenotypic plasticity

2018 ◽  
Author(s):  
Karen D. Williams ◽  
Marla B. Sokolowski
Keyword(s):  
Gene Expression ◽  
Phenotypic Plasticity ◽  
Environmental Change ◽  
Behavioral Plasticity ◽  
Behavioral Flexibility ◽  
Insect Behavior ◽  
Behavioral Variability ◽  
Gene By Environment Interactions ◽  
Affect Gene Expression

Why is there so much variation in insect behavior? This chapter will address the sources of behavioral variability, with a particular focus on phenotypic plasticity. Variation in social, nutritional, and seasonal environmental contexts during development and adulthood can give rise to phenotypic plasticity. To delve into mechanism underlying behavioral flexibility in insects, examples of polyphenisms, a type of phenotypic plasticity, will be discussed. Selected examples reveal that environmental change can affect gene expression, which in turn can affect behavioral plasticity. These changes in gene expression together with gene-by-environment interactions are discussed to illuminate our understanding of insect behavioral plasticity.

Sign in / Sign up

Export Citation Format

Share Document