Macroevolutionary divergence of gene expression driven by selection on protein abundance

Science, Год журнала: 2025, Номер 387(6738), С. 1063 - 1068

Опубликована: Март 6, 2025

The regulation of messenger RNA (mRNA) and protein abundances is well-studied, but less known about the evolutionary processes shaping their relationship. To address this, we derived a new phylogenetic model applied it to multispecies mammalian data. Our analyses reveal (i) strong stabilizing selection on over macroevolutionary time, (ii) mutations affecting mRNA minimally impact abundances, (iii) evolve under align with (iv) adapt faster than owing greater mutational opportunity. These conclusions are supported by comparisons parameters independent functional genomic By decomposing selective influences mRNA-protein dynamics, our approach provides framework for discovering rules that drive divergence in gene expression.

Язык: Английский

---

Molecular concepts to explain heterosis in crops

Trends in Plant Science, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Heterosis describes the superior performance of hybrid plants compared with their genetically distinct parents and is a pillar global food security. Here we review current status molecular dissection heterosis. We discuss how extensive intraspecific structural genomic variation between parental genotypes leads to heterosis by genetic complementation in hybrids. Moreover, survey gene expression contributes hundreds additionally active genes hybrids overdominant single mediate several species. Furthermore, highlight prominent role microbiome improving Taken together, understanding will pave way accelerate productivity more sustainable agriculture.

Язык: Английский

---

Evaluating the Performance of Widely Used Phylogenetic Models for Gene Expression Evolution

Genome Biology and Evolution, Год журнала: 2023, Номер 15(12)

Опубликована: Ноя. 24, 2023

Abstract Phylogenetic comparative methods are increasingly used to test hypotheses about the evolutionary processes that drive divergence in gene expression among species. However, it is unknown whether distributional assumptions of phylogenetic models designed for quantitative phenotypic traits realistic data and importantly, reliability conclusions studies may depend on well described by chosen model. To evaluate this, we first fit several trait evolution 8 previously published datasets, comprising a total 54,774 genes with 145,927 unique gene–tissue combinations. Using developed approach, then assessed how best model set an absolute (not just relative) sense. First, find Ornstein–Uhlenbeck models, which values constrained around optimum, were preferred 66% Second, 61% combinations, best-fit was found perform well; rest be performing poorly at least one statistics examined. Third, when simple do not well, this appears typically consequence failing fully account heterogeneity rate evolution. We advocate assessment performance should become routine component studies; doing so can improve inferences inspire development novel models.

Язык: Английский

---

Unifying approaches from statistical genetics and phylogenetics for mapping phenotypes in structured populations

PLoS Biology, Год журнала: 2024, Номер 22(10), С. e3002847 - e3002847

Опубликована: Окт. 9, 2024

In both statistical genetics and phylogenetics, a major goal is to identify correlations between genetic loci or other aspects of the phenotype environment focal trait. these 2 fields, there are sophisticated but disparate traditions aimed at tasks. The disconnect their respective approaches becoming untenable as questions in medicine, conservation biology, evolutionary biology increasingly rely on integrating data from within among species, once-clear conceptual divisions blurred. To help bridge this divide, we lay out general model describing covariance contributions quantitative phenotypes different individuals. Taking approach shows that standard models (e.g., genome-wide association studies; GWAS) phylogenetic comparative regression) can be interpreted special cases more quantitative-genetic model. fact share same core architecture means build unified understanding strengths limitations methods for controlling structure when testing associations. We develop intuition why spurious may occur analytically conduct population-genetic simulations traits. structural similarity problems phylogenetics enables us take methodological advances one field apply them other. demonstrate by showing how GWAS technique-including relatedness matrix (GRM) well its leading eigenvectors, corresponding principal components genotype matrix, regression model-can mitigate analyses. As case study, re-examine an analysis coevolution expression levels genes across fungal phylogeny show including eigenvectors covariates decreases false positive rate while simultaneously increasing true rate. More generally, work provides foundation integrative processes shape it.

Язык: Английский

---

Ethyl Acetate Extract of Cichorium glandulosum Activates the P21/Nrf2/HO-1 Pathway to Alleviate Oxidative Stress in a Mouse Model of Alcoholic Liver Disease

Metabolites, Год журнала: 2025, Номер 15(1), С. 41 - 41

Опубликована: Янв. 10, 2025

Background: Alcoholic liver disease (ALD) is a significant global health concern, primarily resulting from chronic alcohol consumption, with oxidative stress as key driver. The ethyl acetate extract of Cichorium glandulosum (CGE) exhibits antioxidant and hepatoprotective properties, but its detailed mechanism action against ALD remains unclear. This study investigates the effects mechanisms CGE in alleviating alcohol-induced injury. Methods: Ultra-Performance Liquid Chromatography coupled Quadrupole-Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap-MS) was used to identify components. A C57BL/6J mouse model established via daily oral ethanol (56%) for six weeks, treatment at low (100 mg/kg) high doses (200 mg/kg). Silibinin served positive control. Liver function markers, indicators, inflammatory markers were assessed. Transcriptomic network pharmacology analyses identified genes pathways, validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) Western blotting. Results: UPLC-Q-Orbitrap-MS 81 compounds, mainly including terpenoids, flavonoids, phenylpropanoids. significantly ameliorated injury reducing alanine aminotransferase (ALT), aspartate (AST), alkaline phosphatase (ALP) levels enhancing antioxidative such total capacity (T-AOC) superoxide dismutase (T-SOD) while lowering hepatic malondialdehyde (MDA) levels. Inflammation mitigated through reduced Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1 Beta (IL-1β), C-X-C Motif Chemokine Ligand 10 (CXCL-10). analysis revealed seven antioxidant-related genes, HMOX1, RSAD2, BCL6, CDKN1A, THBD, SLC2A4, TGFβ3, RT-qPCR. activated P21/Nuclear Erythroid 2-Related 2 (Nrf2)/Heme Oxygenase-1 (HO-1) signaling axis, increasing P21, Nrf2, HO-1 protein suppressing Kelch-like ECH-associated Protein 1 (Keap1) expression. Conclusions: mitigates activating P21/Nrf2/HO-1 pathway regulating genes. Its multi-target highlight CGE’s potential promising therapeutic candidate treatment.

Язык: Английский

---

Multilevel gene expression changes in lineages containing adaptive copy number variants

Molecular Biology and Evolution, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Abstract Copy-number variants (CNVs) are an important class of genetic variation that can mediate rapid adaptive evolution. Whereas CNVs increase the relative fitness organism, they also incur a cost due to associated increased gene expression and repetitive DNA. We previously evolved populations Saccharomyces cerevisiae over hundreds generations in glutamine-limited (Gln-) chemostats observed recurrent evolution at GAP1 locus. To understand role plays adaptation, both relation adaptation organism selective condition as consequence CNV, we measured transcriptome, translatome, proteome 4 strains yeast, each with unique their ancestor Gln- conditions. find CNV-amplified genes correlate higher mRNA abundance; however, this effect is reduced level proteome, consistent post-transcriptional dosage compensation. By normalizing by abundance preceding step were able identify widespread differences efficiency expression. Genes significantly different translational enriched for potential regulatory mechanisms including either upstream open reading frames (uORFs), RNA binding sites Ssd1, or both. lower protein encoding proteins complexes. Taken together, our study reveals changes multiple levels lineages containing highlighting diverse ways which genome shapes

Язык: Английский

---

Impact of Neuroimmune System Activation by Adolescent Binge Alcohol Exposure on Adult Neurobiology

Advances in experimental medicine and biology, Год журнала: 2025, Номер unknown, С. 179 - 208

Опубликована: Янв. 1, 2025

Язык: Английский

---

Constraints on the optimization of gene product diversity

Molecular Systems Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract RNA and proteins can have diverse isoforms due to post-transcriptional post-translational modifications. A fundamental question is whether these are mostly beneficial or the result of noisy molecular processes. To assess plausibility explanations, we developed mathematical models depicting different regulatory architectures investigated isoform evolution under multiple population genetic regimes. We found that factors beyond selection, such as effective size number cis -acting loci, significantly influence evolutionary outcomes. sub-optimal phenotypes more likely evolve when populations small and/or -loci large. also discovered opposing selection on - trans loci constrain adaptation, leading a non-monotonic relationship between optimization. More generally, our provide quantitative framework for developing statistical tests analyze empirical data; demonstration this, analyzed A-to-I editing levels in coleoids be largely consistent with non-adaptive explanations.

Язык: Английский

---

Expression of WNT Signaling Genes in the Dorsolateral Prefrontal Cortex in Schizophrenia

Brain Sciences, Год журнала: 2024, Номер 14(7), С. 649 - 649

Опубликована: Июнь 27, 2024

Gene expression alterations in postmortem schizophrenia tissue are well-documented and influenced by genetic, medication, epigenetic factors. The Wingless/Integrated (WNT) signaling pathway, critical for cell growth development, is involved various cellular processes including neurodevelopment synaptic plasticity. Despite its importance, WNT remains understudied schizophrenia, a disorder characterized metabolic bioenergetic defects cortical regions. In this study, we examined the gene of 10 key pathway transcripts: IQGAP1, CTNNβ1, GSK3β, FOXO1, LRP6, MGEA5, TCF4, βTRC, PPP1Cβ, DVL2 dorsolateral prefrontal cortex (DLPFC) using from subjects (n = 20, males, females) compared to age, pH, interval (PMI)-matched controls females). Employing R-shiny application Kaleidoscope, conducted silico “lookup” studies published transcriptomic datasets examine cell- region-level these genes. addition, investigated impact antipsychotics on mRNA genes interest rodent brain datasets. Our findings revealed no significant changes transcript expression; however, analyses previously cell-level indicated antipsychotic-specific modulation certain These results suggest that transcripts may be variably expressed at level antipsychotic treatment, providing novel insights into role pathophysiology schizophrenia.

Язык: Английский

---

Therapeutic Potential of P110 Peptide: New Insights into Treatment of Alzheimer’s Disease

Life, Год журнала: 2023, Номер 13(11), С. 2156 - 2156

Опубликована: Ноя. 2, 2023

Mitochondrial degeneration in various neurodegenerative diseases, specifically Alzheimer's disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores dynamics by acting as an inhibitor of fission. However, the role neuroprotective agent AD remains unclear. Therefore, we performed culture studies evaluate effect on amyloid-β accumulation functioning. Human SH-SY5Y neuronal cells were incubated with 1 µM 10 P110, Real-Time PCR Western blot analysis done quantify expression genes pertaining health. Exposure significantly increased APP mRNA levels at µM, while BACE1 both µM. protein P110. Further, treatment ADAM10 Klotho In addition, exposure active mitochondria ROS live concentrations. Taken together, our results indicate might be useful attenuating generation improving health maintaining function neurons.

Язык: Английский

---