scholarly journals The importance of controlling genetic variation – remarks on ‘Appropriate rearing density in domesticated zebrafish to avoid masculinization: links with the stress response’

2017 ◽  
Vol 220 (21) ◽  
pp. 4078-4078 ◽  
Author(s):  
Thomas A. Delomas ◽  
Konrad Dabrowski
2021 ◽  
Author(s):  
Nikki D. Russell ◽  
Clement Y. Chow

AbstractGenotype x Environment (GxE) interactions occur when environmental conditions drastically change the effect of a genetic variant. In order to truly understand the effect of genetic variation, we need to incorporate multiple environments into our analyses. Many variants, under steady state conditions, may be silent or even have the opposite effect under stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with tissue type and cellular stress. Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. This triggers the unfolded protein response (UPR), a large transcriptional response which attempts to return the cell to homeostasis. This transcriptional response, despite being a well conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal system to study GxE effects. In this study, we sought to better understand how genetic variation alters expression across tissues, in the presence and absence of ER stress. The use of different mouse strains and their F1s allow us to also identify context specific cis- and trans-regulatory mechanisms underlying variable transcriptional responses. We found hundreds of genes that respond to ER stress in a tissue- and/or genotype-dependent manner. Genotype-dependent ER stress-responsive genes are enriched for processes such as protein folding, apoptosis, and protein transport, indicating that some of the variability occurs in canonical ER stress factors. The majority of regulatory mechanisms underlying these variable transcriptional responses derive from cis-regulatory variation and are unique to a given tissue or ER stress state. This study demonstrates the need for incorporating multiple environments in future studies to better elucidate the effect of any particular genetic factor in basic biological pathways, like the ER stress response.Author SummaryThe effect of genetic variation is dependent on environmental context. Here we use genetically diverse mouse strains to understand how genetic variation interacts with stress state to produce variable transcriptional profiles. In this study, we take advantage of the endoplasmic reticulum (ER) stress response which is a large transcriptional response to misfolded proteins. Using this system, we uncovered tissue- and ER stress-specific effects of genetic variation on gene expression. Genes with genotype-dependent variable expression levels in response to ER stress were enriched for canonical ER stress functions, such as protein folding and transport. These variable effects of genetic variation are driven by unique sets of regulatory variation that are only active under context-specific circumstances. The results of this study highlight the importance of including multiple environments and genetic backgrounds when studying the ER stress response and other cellular pathways.


2019 ◽  
Author(s):  
T.M. Houslay ◽  
R.L. Earley ◽  
S.J. White ◽  
W. Lammers ◽  
A.J. Grimmer ◽  
...  

AbstractThe vertebrate stress response comprises a suite of behavioural and physiological traits that must be functionally integrated to ensure organisms cope adaptively with acute stressors. The expectation that natural selection has favoured functional integration leads to a prediction of genetic integration: genetic variation in the stress response should include covariation between its component behavioural and physiological traits. Despite the implications of such genetic integration for our understanding of human and animal health, as well as evolutionary responses to natural and anthropogenic stressors, formal quantitative genetic tests of this prediction are lacking. Here we demonstrate that Trinidadian guppies (Poecilia reticulata) show genetic variation in a suite of behavioural and physiological components of the acute stress response, and that these are indeed integrated into a single major axis of genetic variation. This axis appears to reflect continuous variation in the magnitude of integrated stress responsiveness, rather than variation in ‘coping style’ (a verbal model that postulates equal levels of stress responsiveness will manifest differently across individuals). The genetic integration we find here could either facilitate or constrain evolutionary responses to selection, depending upon the extent to which the direction of selection aligns with this single major axis of genetic covariation among stress response traits. Such integration also suggests that, while stress-related disease typically arises from physiological components of the stress response, selection on the genetically correlated behavioural responses to stress could offer a viable non-invasive route to the genetic improvement of health and welfare in captive animal populations.


1992 ◽  
Vol 4 (1) ◽  
pp. 1-6 ◽  
Author(s):  
M. J. Kebus ◽  
M. T. Collins ◽  
M. S. Brownfield ◽  
C. H. Amundson ◽  
T. B. Kayes ◽  
...  

2019 ◽  
Author(s):  
Rebecca A. Zabinsky ◽  
Jonathan Mares ◽  
Richard She ◽  
Michelle K. Zeman ◽  
Thomas R. Silvers ◽  
...  

ABSTRACTRapid mutation fuels the evolution of many cancers and pathogens. Much of the ensuing genetic variation is detrimental, but cells can survive by limiting the cost of accumulating mutation burden. We investigated this behavior by propagating hypermutating yeast lineages to create independent populations harboring thousands of distinct genetic variants. Mutation rate and spectrum remained unchanged throughout the experiment, yet lesions that arose early were more deleterious than those that arose later. Although the lineages shared no mutations in common, each mounted a similar transcriptional response to mutation burden. The proteins involved in this response formed a highly connected network that has not previously been identified. Inhibiting this response increased the cost of accumulated mutations, selectively killing highly mutated cells. A similar gene expression program exists in hypermutating human cancers and is linked to survival. Our data thus define a conserved stress response that buffers the cost of accumulating genetic lesions and further suggest that this network could be targeted therapeutically.


2019 ◽  
Author(s):  
Amarinder Singh Thind ◽  
Valerio Vitali ◽  
Mario R. Guarracino ◽  
Francesco Catania

AbstractThe pervasiveness of sex despite its well-known costs is a long-standing puzzle in evolutionary biology. Current explanations for the success of sex in nature largely rely on the adaptive significance of the new or rare genotypes that sex may generate. Less explored is the possibility that sex-underlying molecular mechanisms can enhance fitness and convey benefits to the individuals that bear the immediate costs of sex. Here we show that self-fertilization can increase stress resistance in the ciliate Paramecium tetraurelia. This advantage is independent of new genetic variation, coupled with a reduced nutritional input, and offers fresh insights into the mechanistic origin of sex. In addition to providing evidence that the molecular underpinnings of sexual reproduction and the stress response are linked in P. tetraurelia, these findings supply an explanation for the persistence of self-fertilization in this ciliate.


Nature ◽  
2008 ◽  
Vol 452 (7190) ◽  
pp. 997-1001 ◽  
Author(s):  
Zhifeng Zhou ◽  
Guanshan Zhu ◽  
Ahmad R. Hariri ◽  
Mary-Anne Enoch ◽  
David Scott ◽  
...  

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