scholarly journals Genetic variation in aneuploidy prevalence and tolerance across Saccharomyces cerevisiae lineages

Genetics ◽  
2021 ◽  
Vol 217 (4) ◽  
Author(s):  
Eduardo F C Scopel ◽  
James Hose ◽  
Douda Bensasson ◽  
Audrey P Gasch
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Variation ◽  
Genetic Background ◽  
Species Variation ◽  
Unanswered Question ◽  
Fitness Costs ◽  
Chromosome Gain ◽  
Evolutionary Trajectories ◽  
Ecological Associations ◽  
Genetic Makeup

Abstract Individuals carrying an aberrant number of chromosomes can vary widely in their expression of aneuploidy phenotypes. A major unanswered question is the degree to which an individual’s genetic makeup influences its tolerance of karyotypic imbalance. Here we investigated within-species variation in aneuploidy prevalence and tolerance, using Saccharomyces cerevisiae as a model for eukaryotic biology. We analyzed genotypic and phenotypic variation recently published for over 1,000 S. cerevisiae strains spanning dozens of genetically defined clades and ecological associations. Our results show that the prevalence of chromosome gain and loss varies by clade and can be better explained by differences in genetic background than ecology. The relationships between lineages with high aneuploidy frequencies suggest that increased aneuploidy prevalence emerged multiple times in S. cerevisiae evolution. Separate from aneuploidy prevalence, analyzing growth phenotypes revealed that some genetic backgrounds—such as the European Wine lineage—show fitness costs in aneuploids compared to euploids, whereas other clades with high aneuploidy frequencies show little evidence of major deleterious effects. Our analysis confirms that chromosome gain can produce phenotypic benefits, which could influence evolutionary trajectories. These results have important implications for understanding genetic variation in aneuploidy prevalence in health, disease, and evolution.

scholarly journals Genetic variation in aneuploidy prevalence and tolerance across the Saccharomyces cerevisiae phylogeny

2020 ◽  
Author(s):  
Eduardo FC Scopel ◽  
James Hose ◽  
Douda Bensasson ◽  
Audrey Gasch
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Variation ◽  
Genetic Background ◽  
Unanswered Question ◽  
Fitness Costs ◽  
Chromosome Duplication ◽  
Evolutionary Trajectories ◽  
Selective Forces ◽  
Ecological Associations ◽  
Genetic Makeup

Individuals carrying an aberrant number of chromosomes can vary widely in their expression of aneuploidy phenotypes. A major unanswered question is the degree to which an individual's genetic makeup influences its tolerance of karyotypic imbalance. Here we took a population genetics perspective to investigate the selective forces influencing aneuploidy prevalence in Saccharomyces cerevisiae populations as a model for eukaryotic biology. We analyzed genotypic and phenotypic variation recently published for over 1,000 S. cerevisiae strains spanning dozens of genetically defined clades and ecological associations. Our results show that the prevalence of chromosome gain and loss varies by clade and can be better explained by differences in genetic background than ecology. The phylogenetic context of lineages showing high aneuploidy rates suggests that increased aneuploidy frequency arose multiple times in S. cerevisiae evolution. Separate from aneuploidy frequency, analyzing growth phenotypes reveals that some backgrounds – such as European Wine strains – show fitness costs upon chromosome duplication, whereas other clades with high aneuploidy rates show little evidence of major deleterious effects. Our analysis confirms that chromosome amplification can produce phenotypic benefits that can influence evolutionary trajectories. These results have important implications for understanding genetic variation in aneuploidy prevalence in health, disease, and evolution.

scholarly journals Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories

2021 ◽  
Author(s):  
DeElegant Robinson ◽  
Michael Place ◽  
James Hose ◽  
Adam Jochem ◽  
Audrey P Gasch
Keyword(s):  
Genetic Background ◽  
Natural Variation ◽  
Gene Overexpression ◽  
Fitness Costs ◽  
Resource Limitations ◽  
Specific Effects ◽  
Term Evolution ◽  
Number Variation ◽  
Evolutionary Trajectories

Copy number variation (CNV) through gene or chromosome amplification provides a route for rapid phenotypic variation and supports long-term evolution of gene functions. Although the evolutionary importance of CNV is known, little is understood about how genetic background influences CNV tolerance. Here, we measured fitness costs of over 4,000 over-expressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds.

scholarly journals Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
DeElegant Robinson ◽  
Mike Place ◽  
James Hose ◽  
Adam Jochem ◽  
Audrey P Gasch
Keyword(s):  
Genetic Background ◽  
Natural Variation ◽  
Gene Overexpression ◽  
Fitness Costs ◽  
Resource Limitations ◽  
Specific Effects ◽  
Term Evolution ◽  
Number Variation ◽  
Evolutionary Trajectories

Copy number variation (CNV) through gene or chromosome amplification provides a route for rapid phenotypic variation and supports long-term evolution of gene functions. Although the evolutionary importance of CNV is known, little is understood about how genetic background influences CNV tolerance. Here, we measured fitness costs of over 4,000 over-expressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds.

Genetic background of cholesterol absorption efficacy. The role of Niemann–Pick C1-like 1 receptor and its genetic variation in lipid metabolism

2010 ◽  
Vol 151 (34) ◽  
pp. 1376-1383 ◽  
Author(s):  
Mariann Harangi ◽  
István Balogh ◽  
János Harangi ◽  
György Paragh
Keyword(s):  
Genetic Variation ◽  
Lipid Metabolism ◽  
Genetic Background ◽  
Cholesterol Absorption ◽  
Niemann Pick

A Niemann–Pick C1-like-1 egy szterolfelismerő domént tartalmazó membránfehérje, amelyet nagy számban expresszálnak csúcsi felszínükön a bélhámsejtek. Az utóbbi évek vizsgálatai azt igazolták, hogy ez a fehérje szükséges a szabad koleszterin bejutásához a bélhámsejtekbe a bél lumenéből. Biokémiai vizsgálatok azt igazolták, hogy a Niemann–Pick C1-like-1-hez kötődik az ezetimib, amely egy hatékony koleszterinfelszívódást gátló szer. A bélből történő koleszterinfelszívódás ütemében és az ezetimibkezelés hatékonyságában tapasztalt egyéni eltérések hátterében felmerült néhány Niemann–Pick C1-like-1 génvariáció oki szerepe.

scholarly journals Specific phenotypic, genomic, and fitness evolutionary trajectories toward streptomycin resistance induced by pesticide co-stressors in Escherichia coli

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Yue Xing ◽  
Xiaoxi Kang ◽  
Siwei Zhang ◽  
Yujie Men
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Selective Pressure ◽  
Fold Increase ◽  
Streptomycin Resistance ◽  
Evolutionary Stage ◽  
Fitness Costs ◽  
Evolutionary Trajectories ◽  
K 12 ◽  
Late Stages

AbstractTo explore how co-occurring non-antibiotic environmental stressors affect evolutionary trajectories toward antibiotic resistance, we exposed susceptible Escherichia coli K-12 populations to environmentally relevant levels of pesticides and streptomycin for 500 generations. The coexposure substantially changed the phenotypic, genotypic, and fitness evolutionary trajectories, resulting in much stronger streptomycin resistance (>15-fold increase) of the populations. Antibiotic target modification mutations in rpsL and rsmG, which emerged and dominated at late stages of evolution, conferred the strong resistance even with less than 1% abundance, while the off-target mutations in nuoG, nuoL, glnE, and yaiW dominated at early stages only led to mild resistance (2.5–6-fold increase). Moreover, the strongly resistant mutants exhibited lower fitness costs even without the selective pressure and had lower minimal selection concentrations than the mildly resistant ones. Removal of the selective pressure did not reverse the strong resistance of coexposed populations at a later evolutionary stage. The findings suggest higher risks of the selection and propagation of strong antibiotic resistance in environments potentially impacted by antibiotics and pesticides.

Abstract 11511: Genetic Variation in Retinal Vascular Patterning Predicts Variation in Pial Collateral Extent and Infarct Volume After Middle Cerebral Artery Occlusion

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pranay Prabhakar ◽  
Hua Zhang ◽  
De Chen ◽  
Stephen Lockett ◽  
James E Faber
Keyword(s):  
Genetic Variation ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Genetic Background ◽  
Infarct Volume ◽  
Indirect Evidence ◽  
Artery Occlusion ◽  
Stroke Severity ◽  
Cerebral Artery Occlusion

Introduction: The presence of a native (pre-existing) collateral circulation in tissues lessens injury in stroke and other occlusive diseases. However, differences in genetic background are accompanied by wide variation in the number and diameter (extent) of native collaterals in mice, resulting in large variation in protection. Indirect evidence suggests a similar wide variation also exists in humans. However, methods of measurement in humans are indirect, invasive and not widely available. Hypothesis: We sought to determine if differences in genetic background in mice result in variation in branch-patterning of the retinal circulation, and if these differences predict differences in collateral extent and, in turn, differences in severity of ischemic stroke. Methods: Patterning metrics were obtained for the retinal arterial trees of 10 mouse strains (n=8 per strain) that differ widely in collateral extent in brain and other tissues. We also obtained pial collateral number and diameter, and infarct volume 24h after permanent middle cerebral artery occlusion. Forward- and reverse-stepwise multivariate regression analysis was conducted and model performance assessed using K-fold cross-validation. Results: Twenty-one metrics varied significantly with genetic strain (p<0.01). Ten metrics (eg, vessel caliber, bifurcation angle, lacunarity, optimality, branch length) strongly predicted collateral number and diameter across 7 regression models. The best models closely predicted (p<0.0001) collateral number (K-fold R 2 =0.83-0.98), diameter (0.73-0.88) and infarct volume (0.85-0.87). Conclusions: Differences in retinal tree patterning are specified by genetic background and closely predict genetic variation in pial collateral extent and, in turn, stroke severity. If these findings can be confirmed in humans, and given that genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could be developed as a biomarker for collateral extent in brain and other tissues. This could aid prediction of the risk-severity of tissue injury in occlusive disease as well as stratification of patients for treatment options and enrollment in clinical studies.

The coevolution of host resistance and parasitoid virulence

Parasitology ◽  
1998 ◽  
Vol 116 (S1) ◽  
pp. S29-S45 ◽  
Author(s):  
A. R. Kraaijeveld ◽  
J. J. M. Van Alphen ◽  
H. C. J. Godfray
Keyword(s):  
Genetic Variation ◽  
Artificial Selection ◽  
Host Resistance ◽  
Genetic Basis ◽  
Isofemale Line ◽  
Fitness Costs ◽  
Geographical Patterns ◽  
Wide Range ◽  
Great Scope ◽  
Fertile Area

SummaryHost-parasitoid interactions are abundant in nature and offer great scope for the study of coevolution. A particularly fertile area is the interaction between internal feeding parasitoids and their hosts. Hosts have evolved a variety of means of combating parasitoids, in particular cellular encapsulation, while parasitoids have evolved a wide range of countermeasures. Studies of the evolution of host resistance and parasitoid virulence are reviewed, with an emphasis on work involvingDrosophilaand its parasitoids. Genetic variation in both traits has been demonstrated using isofemale line and artificial selection techniques. Recent studies have investigated the fitness costs of maintaining the ability to resist parasitoids, the comparative fitness of flies that have successfully defended themselves against parasitoids, and the degree to which resistance and virulence act against one or more species of host or parasitoid. A number of studies have examined geographical patterns, and sought to look for local adaptation; or have compared the traits across a range of species. Finally, the physiological and genetic basis of change in resistance and virulence is being investigated. While concentrating onDrosophila, the limited amount of work on different systems is reviewed, and other possible areas of coevolution in host-parasitoid interactions are briefly discussed.

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