Project description:The antagonistic pleiotropy theory of aging predicts genetic trade-offs between early-life and late-life fitness. However, empirical evidence for these trade-offs in vertebrates remains scarce, particularly in the context of ecologically relevant life histories. Here, we identify vestigial-like 3 (vgll3), a transcription cofactor previously linked with age at maturity in humans and Atlantic salmon through GWAS studies, as an antagonistically pleiotropic gene in turquoise killifish (Nothobranchius furzeri). By disrupting two conserved vgll3 isoforms, we show that reduction of vgll3, in an isoform- or dose-dependent manner, accelerated male growth and reproductive development. This indicates that vgll3 regulates male sexual maturity. However, early-life benefits come at a late-life cost, as older mutant males with a disrupted long isoform develop melanoma-like tumors, validated via transplantation into immunodeficient rag2 models, and exhibit increased age-related mortality rate. These findings highlight vgll3 as a key regulator of vertebrate life-history trade-offs, balancing early-life fitness with late-life disease risks.
Project description:Exploring molecular details of carbon utilization trade-offs in galactose-evolved yeast Adaptively evolved yeast mutants on galactose for around 400 generations showed diminished growth and carbon uptake rates on glucose. Genome-scale approaches were applied to characterize the molecular genetic basis of these trade-offs in carbon source utilization. Engineered mutants showing trade-offs in a specific carbon uptake rate between both carbons were used as controls. The transcriptional responses of the evolved mutants were almost identical during growth on both carbon sources. These carbon-independent conserved patterns were clearly observed in specific pathways and genes. Up-regulation of PGM2, a confirmed beneficial genetic change for improving galactose utilization was preserved on both carbons. In addition, HXK1, GLK1 and genes involved in reserve carbohydrate metabolism were up-regulated, while HXK2 was down-regulated. Genes that have a transcription factor binding site for Gis1p, Rph1p, Msn2/4p and Nrg1p were up-regulated. These results indicated changes in the metabolic pathways involved in metabolism of both carbons and in nutrient signaling pathway. The concentration profile of trehalose and glycogen supported these findings. Mutations in RAS2 and ERG5 genes were selected because of their beneficial and neutral effect on galactose utilization, respectively in our previous study. Site-directed mutants containing galactose-beneficial mutations in RAS2 only resulted in a significant decrease in glucose utilization. Integration of all these analyses clearly suggest an antagonistic pleiotropic trade-off in carbon source utilization caused by changes in regulatory region, and we hereby demonstrate how systems biology can be used to gain insight into evolutionary processes at the molecular level. Yeast galactose evolved mutants having improved galactose availability were grown on aerobic batch with glucose as carbon source
Project description:The transcriptome and DGE analysis of the fat body and ovary of L. migratoria based on the Illumina short-read sequencing technology and De novo assembly. Research on the trade-offs between immunity and reproduction is contributing significantly to the understanding of the fitness of organisms in nature.
2017-05-01 | GSE57437 | GEO
Project description:Trade-offs constrain adaptive pathways to T6SS survival
Project description:Exploring molecular details of carbon utilization trade-offs in galactose-evolved yeast Adaptively evolved yeast mutants on galactose for around 400 generations showed diminished growth and carbon uptake rates on glucose. Genome-scale approaches were applied to characterize the molecular genetic basis of these trade-offs in carbon source utilization. Engineered mutants showing trade-offs in a specific carbon uptake rate between both carbons were used as controls. The transcriptional responses of the evolved mutants were almost identical during growth on both carbon sources. These carbon-independent conserved patterns were clearly observed in specific pathways and genes. Up-regulation of PGM2, a confirmed beneficial genetic change for improving galactose utilization was preserved on both carbons. In addition, HXK1, GLK1 and genes involved in reserve carbohydrate metabolism were up-regulated, while HXK2 was down-regulated. Genes that have a transcription factor binding site for Gis1p, Rph1p, Msn2/4p and Nrg1p were up-regulated. These results indicated changes in the metabolic pathways involved in metabolism of both carbons and in nutrient signaling pathway. The concentration profile of trehalose and glycogen supported these findings. Mutations in RAS2 and ERG5 genes were selected because of their beneficial and neutral effect on galactose utilization, respectively in our previous study. Site-directed mutants containing galactose-beneficial mutations in RAS2 only resulted in a significant decrease in glucose utilization. Integration of all these analyses clearly suggest an antagonistic pleiotropic trade-off in carbon source utilization caused by changes in regulatory region, and we hereby demonstrate how systems biology can be used to gain insight into evolutionary processes at the molecular level.
Project description:The sole gain of laterally acquired virulence genes does not fully explain the transition of environmental strains into human pathogens. To date, the specific molecular drivers and fitness trade-offs that enable some strains within a population to undergo this process remain enigmatic. Here, we describe a small RNA (sRNA) with a unique modular structure that shapes the evolution of toxigenic Vibrio cholerae, the agent of cholera. The sRNA comprises of a highly variable 5’ module located within the ompU ORF and a conserved 3’ one downstream from the gene. The bimodular nature of the OmpU-encoded sRNA (OueS) generates allelic variants that differentially contribute to the emergence of virulence potential in some strains and associated fitness trade-offs between human infection and environmental survival. Unlike environmental counterparts, the OueS allele from toxigenic strains controls phenotypes essential during host colonization: a) stringently inhibits biofilm formation by suppressing the iron-responsive sRNA RyhB, and b) confers resistance against intestinal bacteriophages by activating the CBASS phage defense system. Toxigenic OueS is also required for successful intestinal colonization and acts as a functional surrogate of the master virulence regulator ToxR, controlling over 84% of its regulome. On the other hand, strains encoding environmental alleles of OueS exhibit higher competitive fitness than those harboring toxigenic ones during colonization of natural reservoirs such as crustaceans (Artemia salina) and phytoplankton (Microcystis aeruginosa). These results uncover the fitness trade-offs between human infection and environmental survival and costs associated with pathogen emergence.
Project description:The sole gain of laterally acquired virulence genes does not fully explain the transition of environmental strains into human pathogens. To date, the specific molecular drivers and fitness trade-offs that enable some strains within a population to undergo this process remain enigmatic. Here, we describe a small RNA (sRNA) with a unique modular structure that shapes the evolution of toxigenic Vibrio cholerae, the agent of cholera. The sRNA comprises of a highly variable 5’ module located within the ompU ORF and a conserved 3’ one downstream from the gene. The bimodular nature of the OmpU-encoded sRNA (OueS) generates allelic variants that differentially contribute to the emergence of virulence potential in some strains and associated fitness trade-offs between human infection and environmental survival. Unlike environmental counterparts, the OueS allele from toxigenic strains controls phenotypes essential during host colonization: a) stringently inhibits biofilm formation by suppressing the iron-responsive sRNA RyhB, and b) confers resistance against intestinal bacteriophages by activating the CBASS phage defense system. Toxigenic OueS is also required for successful intestinal colonization and acts as a functional surrogate of the master virulence regulator ToxR, controlling over 84% of its regulome. On the other hand, strains encoding environmental alleles of OueS exhibit higher competitive fitness than those harboring toxigenic ones during colonization of natural reservoirs such as crustaceans (Artemia salina) and phytoplankton (Microcystis aeruginosa). These results uncover the fitness trade-offs between human infection and environmental survival and costs associated with pathogen emergence.
2026-04-03 | GSE272767 | GEO
Project description:Negative trade-offs shape the evolution of dosage sensitivity
Project description:Under disease stress, activation of defense response in plants often comes with the cost of a reduction in growth and yield, which is referred as the growth-defense trade-off. The microorganisms which can be recruited by plants to mitigate the growth-defense trade-off are of great value in crop breeding. The proteomic, physiological and transcriptional profiling data offer insights into the molecular basis underlying the balancing between defense and growth in endophyte-rice symbiont. The findings provide an example for the endophyte-mediated modulation of growth-defense trade-offs in plants and indicated the promising application of endophytic actinobacterial strains in agriculture to breed “microbe-optimized crops”.