scholarly journals Dissection of Complex, Fitness-Related Traits in Multiple Drosophila Mapping Populations Offers Insight into the Genetic Control of Stress Resistance

Genetics ◽  
2019 ◽  
Vol 211 (4) ◽  
pp. 1449-1467 ◽  
Author(s):  
Elizabeth R. Everman ◽  
Casey L. McNeil ◽  
Jennifer L. Hackett ◽  
Clint L. Bain ◽  
Stuart J. Macdonald
2014 ◽  
Vol 14 (1) ◽  
pp. 40 ◽  
Author(s):  
Francisco J Escaray ◽  
Valentina Passeri ◽  
Florencia M Babuin ◽  
Francisco Marco ◽  
Pedro Carrasco ◽  
...  

2021 ◽  
Author(s):  
Arin B Aurora ◽  
Vishal Khivansara ◽  
Ashley Leach ◽  
Jennifer G Gill ◽  
Misty Martin-Sandoval ◽  
...  

The pentose phosphate pathway is a major source of NADPH for oxidative stress resistance in cancer cells but there is limited insight into its role in metastasis, when some cancer cells experience high levels of oxidative stress. To test this, we mutated the substrate binding site of Glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pentose phosphate pathway, in patient-derived melanomas. G6PD mutant melanomas had significantly decreased G6PD enzymatic activity and depletion of intermediates in the oxidative branch of the pentose phosphate pathway. Reduced G6PD function had little effect on the formation of primary subcutaneous tumors but when these tumors spontaneously metastasized the frequency of circulating melanoma cells in the blood and metastatic disease burden were significantly reduced. G6PD mutant melanomas exhibited increased levels of reactive oxygen species (ROS), decreased NADPH levels, and depleted glutathione as compared to control melanomas. G6PD mutant melanomas compensated for this increase in oxidative stress by increasing the production of NADPH through glutaminolysis. This generated a new metabolic vulnerability as G6PD mutant melanomas were more dependent upon glutamine as compared to control melanomas. The oxidative pentose phosphate pathway and compensatory glutaminolysis thus confer layered protection against oxidative stress during metastasis.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Dmitry E Andreev ◽  
Maxim Arnold ◽  
Stephen J Kiniry ◽  
Gary Loughran ◽  
Audrey M Michel ◽  
...  

Translation initiation is the rate-limiting step of protein synthesis that is downregulated during the Integrated Stress Response (ISR). Previously, we demonstrated that most human mRNAs that are resistant to this inhibition possess translated upstream open reading frames (uORFs), and that in some cases a single uORF is sufficient for the resistance. Here we developed a computational model of Initiation Complexes Interference with Elongating Ribosomes (ICIER) to gain insight into the mechanism. We explored the relationship between the flux of scanning ribosomes upstream and downstream of a single uORF depending on uORF features. Paradoxically, our analysis predicts that reducing ribosome flux upstream of certain uORFs increases initiation downstream. The model supports the derepression of downstream translation as a general mechanism of uORF-mediated stress resistance. It predicts that stress resistance can be achieved with long slowly decoded uORFs that do not favor translation reinitiation and that start with initiators of low leakiness.


2009 ◽  
Vol 296 (6) ◽  
pp. R1847-R1854 ◽  
Author(s):  
Molly K. Burke ◽  
Michael R. Rose

Experimental evolution is a powerful approach that can be used for the study of adaptation. Evolutionary biologists often use Drosophila as a model organism in experiments that test theories about the evolution of traits related to fitness. Such evolution experiments can take three forms: direct selection for a trait of interest; surveys of traits of interest in populations selected for other traits; and reverse selection. We review some of the Drosophila experiments that have provided insight into both the evolution of particular physiological traits and the correlations between physiological and life history traits, focusing on stress resistance. The most common artifacts that can obscure the results from evolution experiments are discussed. We also include a treatment of genomic technologies that are now available for the Drosophila model. The primary goal of this review is to introduce the kind of experimental evolution strategies and technologies that evolutionary physiologists might use in the future.


2017 ◽  
Vol 83 (22) ◽  
Author(s):  
Wen Liu ◽  
Lijuan Cui ◽  
Haiyan Xu ◽  
Zhaoxia Zhu ◽  
Xiang Gao

ABSTRACT A dense exopolysaccharide (EPS) matrix is crucial for cyanobacterial survival in terrestrial xeric environments, in which cyanobacteria undergo frequent expansion and shrinkage processes during environmental desiccation-rehydration cycles. However, it is unclear how terrestrial cyanobacteria coordinate the structural dynamics of the EPS matrix upon expansion and shrinkage to avoid potential mechanical stress while benefiting from the matrix. In the present study, we sought to answer this question by investigating the gene expression, protein dynamics, enzymatic characteristics, and biological roles of WspA, an abundantly secreted protein, in the representative terrestrial cyanobacterium Nostoc flagelliforme. The results demonstrated that WspA is a novel β-galactosidase that facilitates softening of the EPS matrix by breaking the polysaccharide backbone under substantial moisture or facilitates the thickening and relinkage of the broken matrix during the drying process, and thus these regulations are well correlated with moisture availability or desiccation-rehydration cycles. This coordination of flexibility and rigidity of the cyanobacterial extracellular matrix may contribute to a favorable balance of cell growth and stress resistance in xeric environments. IMPORTANCE How the exopolysaccharide matrix is dynamically coordinated by exoproteins to cope with frequent expansion and shrinkage processes in terrestrial colonial cyanobacteria remains unclear. Here we elucidated the biochemical identity and biological roles of a dominant exoprotein in these regulation processes. Our study thus gained insight into this regulative mechanism in cyanobacteria to combat periodic desiccation. In addition, the filamentous drought-adapted cyanobacterium Nostoc flagelliforme serves as an ideal model for us to explore this issue in this study.


2019 ◽  
Vol 19 (3) ◽  
Author(s):  
Chun-Hong Zhang ◽  
Min-Jing Zhang ◽  
Xiao-Xiao Shi ◽  
Cungui Mao ◽  
Zeng-Rong Zhu

Abstract Alkaline ceramidase (Dacer) in Drosophila melanogaster was demonstrated to be resistant to paraquat-induced oxidative stress. However, the underlying mechanism for this resistance remained unclear. Here, we showed that sphingosine feeding triggered the accumulation of hydrogen peroxide (H2O2). Dacer-deficient D. melanogaster (Dacer mutant) has higher catalase (CAT) activity and CAT transcription level, leading to higher resistance to oxidative stress induced by paraquat. By performing a quantitative proteomic analysis, we identified 79 differentially expressed proteins in comparing Dacer mutant to wild type. Three oxidoreductases, including two cytochrome P450 (CG3050, CG9438) and an oxoglutarate/iron-dependent dioxygenase (CG17807), were most significantly upregulated in Dacer mutant. We presumed that altered antioxidative activity in Dacer mutant might be responsible for increased oxidative stress resistance. Our work provides a novel insight into the oxidative antistress response in D. melanogaster.


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