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Antigen-receptor stimulation drives purifying selection against pathogenic mitochondrial DNA variants that dysregulate lymphocyte responses

ABSTRACT: Antigen-receptor stimulation drives purifying selection against pathogenic mitochondrial DNA variants that dysregulate lymphocyte responses

PROVIDER: PRJNA758153 | ENA |

REPOSITORIES: ENA

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Antigen-receptor stimulation drives purifying selection against pathogenic mitochondrial DNA variants that dysregulate lymphocyte responses

Project description:Metabolic transcriptomic signatures of CD8+ T cells during timecourse activation were profiled in CD8 T cells isolated from 4 WT and 4 C5024T mice. Mice were age (2-month-old) and sex matched. Briefly, for each mouse, freshly purified (negative selection) splenic naïve CD8+ T cells were seeded at a density of 200,000 cells/well and activated using a 1:1 (bead:cell) ratio with Dynabeads Mouse T-Activator CD3/CD28 for 6 and 96 hr at 37oC (5% CO2) . 200,000 ex vivo purify ed naïve CD8+ T cells were collected for baseline (0 hr) measurement.

2021-08-27 | GSE182887 | GEO

Purifying selection acting on the sequence of highly expressed proteins in the microevolution

Project description:Constraints on the rate of protein sequence evolution have been a central question in evolutionary biology. Orthology analysis between closely related species has revealed that the evolutionary speed is constrained by the expression level, with highly expressed proteins evolving slowly. This negative correlation between expression levels and evolutionary rates (known as the E-R anticorrelation) has already been widely observed in past macroevolution between species, for example, between Escherichia coli and Salmonella. However, it remains unclear whether this seemingly general law also governs microevolution, including past and de novo, within a species. To explore the ubiquitous impact of expression level on molecular evolution in bacteria, we analysed genome sequences for 99 strains of E. coli for microevolution in nature. We also analysed genomic mutations accumulated under laboratory conditions as a model of de novo microevolution. Here, we show that the E-R anticorrelation is significant in both past microevolution and de novo evolution in E. coli. Our data also indicate that purifying selection acting on highly expressed genes contributes to the ubiquity of the E-R anticorrelation. This study confirmed ongoing purifying selection acting on highly expressed genes, and implied that expression level has a ubiquitous impact on the speed of molecular diversification evolution in bacteria.

2022-09-01 | GSE189008 | GEO

Plant Y-chromosome degeneration is retarded by haploid purifying selection.

Project description:Plant Y-chromosome degeneration is retarded by haploid purifying selection.

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Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells.

Project description:Many mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA). Patients' cells contain a mixture of mutant and nonmutant mtDNA (a phenomenon called heteroplasmy). The proportion of mutant mtDNA varies across patients and among tissues within a patient. We simultaneously assayed single-cell heteroplasmy and cell state in thousands of blood cells obtained from three unrelated patients who had A3243G-associated mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. We observed a broad range of heteroplasmy across all cell types but also found markedly reduced heteroplasmy in T cells, a finding consistent with purifying selection within this lineage. We observed this pattern in six additional patients who had heteroplasmic A3243G without strokelike episodes. (Funded by the Marriott Foundation and others.).

| S-EPMC7593775 | biostudies-literature

altered bovine lymphocyte secretome after pokeweed mitogen stimulation

Project description:Vaccination with a new vaccine against bovine viral diarrhea (BVD) caused unwanted immune reactions through alloreactive antibody production in 5–10% of vaccinated cows. Transfer of these alloreactive antibodies via colostrum caused highly lethal (90%) bovine neonatal pancytopenia (BNP) in calves. Despite the assumption of an immune deviant lymphocyte (PBL) phenotype, the exact immunological mechanisms driving these unwanted immune reactions are not fully understood to date. To gain deeper insight into these mechanisms, we analyzed the PBL secretome from alloreactive antibody producers (BNP cows) and non-alloreactive responders (controls) after stimulation with pokeweed mitogen (PWM).

2022-02-10 | PXD017892 | Pride

Changes in bovine Lymphocyte proteome after stimulation with pokeweed mitogen

Project description:A new vaccine against bovine viral diarrhea (BVD) induced unwanted immune reactions with production of alloreactive antibodies in 5–10% of vaccinated cows. Transfer of these antibodies via colostrum caused bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date, however, an immune deviant phenotype of immune cells is assumed. To gain deeper insight into disease onset and pathogenesis, we analyzed the lymphocyte (PBL) proteome from alloreactive antibody producers (BNP cows) and non-responders (controls) after stimulation with PWM.

2022-02-10 | PXD017350 | Pride

The genomic distribution of transposable elements is driven by spatially variable purifying selection

Project description:The genomic distribution of transposable elements is driven by spatially variable purifying selection

| PRJEB54573 | ENA

Purifying selection acting on the sequence of highly expressed proteins in the microevolution

Project description:Purifying selection acting on the sequence of highly expressed proteins in the microevolution

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Analysis of Efg1 co-purifying proteins

Project description:Analysis of Efg1 co-purifying proteins in comparison to Kre33 particle

2023-11-27 | PXD036987 | Pride

Analysis of Efg1 co-purifying proteins

Project description:Analysis of Efg1 co-purifying proteins in comparison to Bud22 particle