ADAPTIVE DIVERGENCE BETWEEN FRESHWATER AND MARINE STICKLEBACKS: INSIGHTS INTO THE ROLE OF PHENOTYPIC PLASTICITY FROM AN INTEGRATED ANALYSIS OF CANDIDATE GENE EXPRESSION

ObjectiveThe pathophysiology of aldosterone-producing adenomas (APA) has been investigated intensively through genetic and genomic approaches. However, the role of epigenetics in APA is not fully understood. In the present study, we explored the relationship between gene expression and DNA methylation status in APA.MethodsWe conducted an integrated analysis of transcriptome and methylome data of paired APA-adjacent adrenal gland (AAG) samples from the same patient. The adrenal specimens were obtained from seven Japanese patients with APA who underwent adrenalectomy. Gene expression and genome-wide CpG methylation profiles were obtained from RNA and DNA samples that were extracted from those seven paired tissues.ResultsMethylome analysis showed global CpG hypomethylation in APA relative to AAG. The integration of gene expression and methylation status showed that 34 genes were up-regulated with CpG hypomethylation in APA. Of these, three genes (CYP11B2, MC2R, and HPX) may be related to aldosterone production, and five genes (PRRX1, RAB38, FAP, GCNT2, and ASB4) are potentially involved in tumorigenesis.ConclusionThe present study is the first methylome analysis to compare APA with AAG in the same patients. Our integrated analysis of transcriptome and methylome revealed DNA hypomethylation in APA and identified several up-regulated genes with DNA hypomethylation that may be involved in aldosterone production and tumorigenesis.

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Epigenetic Influences on Plant Responses to the Environment [University of Wisconsin - Oshkosh]

Journal of Student Research ◽

10.47611/jsr.vi.624 ◽

2019 ◽

Author(s):

Angela L Vickman ◽

Travis Smith ◽

Hayley Vandenboom ◽

Lisa A. Dorn

Keyword(s):

Gene Expression ◽

Phenotypic Plasticity ◽

Molecular Mechanisms ◽

Molecular Level ◽

Physical Structure ◽

Plant Responses ◽

Appropriate Behavior ◽

Stressful Environment ◽

University Of Wisconsin

Plants and animals may respond to changes in the environment at the molecular level by changing the amount of a gene product (a protein) to generate the appropriate behavior or physical structure (a phenotype) for that environment. For example, an extremely stressful environment can cause plants to reproduce immediately rather than waiting for conditions to improve. The molecular mechanisms for changing phenotype with environment (phenotypic plasticity) are not clear, however previous studies have shown plasticity may be the result of failing to change expression to maintain a phenotype or a deliberate change in expression altering the phenotype. To explore the molecular mechanisms underlying phenotypic plasticity, I am using a minION sequencing apparatus to re-sequence three inbred lines of Arabidopsis thaliana with extreme phenotypic plasticity differences and gene expression differences with the environment. I will specifically explore the role of methylated cytosines and adenines in gene expression.

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Genetic and Epigenetic Alterations Induced by Pesticide Exposure: Integrated Analysis of Gene Expression, microRNA Expression and DNA Methylation Datasets

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168697 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8697

Author(s):

Federica Giambò ◽

Gian Leone ◽

Giuseppe Gattuso ◽

Roberta Rizzo ◽

Alessia Cosentino ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Pesticide Exposure ◽

Methylation Status ◽

Microrna Expression ◽

Integrated Analysis ◽

Epigenetic Alterations ◽

Expression Levels ◽

Prediction Tools

Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.

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Systematic integrated analysis of genetic and epigenetic variation in diabetic kidney disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2005905117 ◽

2020 ◽

Vol 117 (46) ◽

pp. 29013-29024

Author(s):

Xin Sheng ◽

Chengxiang Qiu ◽

Hongbo Liu ◽

Caroline Gluck ◽

Jesse Y. Hsu ◽

...

Keyword(s):

Gene Expression ◽

Kidney Disease ◽

Kidney Function ◽

Diabetic Kidney Disease ◽

Genetic Variations ◽

Integrated Analysis ◽

Disease Development ◽

Diabetic Kidney ◽

Genotype Effect

Poor metabolic control and host genetic predisposition are critical for diabetic kidney disease (DKD) development. The epigenome integrates information from sequence variations and metabolic alterations. Here, we performed a genome-wide methylome association analysis in 500 subjects with DKD from the Chronic Renal Insufficiency Cohort for DKD phenotypes, including glycemic control, albuminuria, kidney function, and kidney function decline. We show distinct methylation patterns associated with each phenotype. We define methylation variations that are associated with underlying nucleotide variations (methylation quantitative trait loci) and show that underlying genetic variations are important drivers of methylation changes. We implemented Bayesian multitrait colocalization analysis (moloc) and summary data-based Mendelian randomization to systematically annotate genomic regions that show association with kidney function, methylation, and gene expression. We prioritized 40 loci, where methylation and gene-expression changes likely mediate the genotype effect on kidney disease development. Functional annotation suggested the role of inflammation, specifically, apoptotic cell clearance and complement activation in kidney disease development. Our study defines methylation changes associated with DKD phenotypes, the key role of underlying genetic variations driving methylation variations, and prioritizes methylome and gene-expression changes that likely mediate the genotype effect on kidney disease pathogenesis.

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The role of genomic vs. epigenomic variation in shaping patterns of convergent transcriptomic variation across continents in a young species complex

10.1101/784231 ◽

2019 ◽

Author(s):

Clément Rougeux ◽

Martin Laporte ◽

Pierre-Alexandre Gagnaire ◽

Louis Bernatchez

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Adaptive Divergence ◽

Relative Role ◽

Gene Expression Variation ◽

Genomic Changes ◽

Expression Variation ◽

Relative Contribution ◽

Variation Explained

ABSTRACTRepeated adaptive divergence in replicates of phenotypic diversification offers a propitious context to identify the molecular bases associated to adaptive divergence. A currently hotly debated topic pertains to the relative role of genomic vs. epigenomic variation in shaping patterns of phenotypic variation at the gene expression level. Here, we combined genomic, epigenomic and transcriptomic information from 64 individuals in order to quantify the relative role of SNPs and DNA methylation variation in the repeated evolution of four limnetic-benthic whitefish species pairs from Europe and North America. We first found evidence for 149 convergent differentially methylated regions (DMRs) between species across continents, which significantly influenced levels of gene expression. Hyper-methylated DMRs in the limnetic species were globally associated to an expression repression relatively to benthic species, and inversely. Furthermore, we identified 108 convergent genetic variants (eQTLs) associated to gene expression differences between species. Gene expression differences were more pronounced in genes harbouring eQTL compared to those associated with DMRs, thus revealing a greater effect of eQTLs on gene expression. Multivariate analyses allowed partitioning the relative contribution of epi-/genomic changes and their association to gene expression variation. Most of the gene expression variation was significantly explained by genomic (4.1%) and putatively genomic-epigenomic interactive variation (46.7%), while “pure” epigenomic variation explained marginally 2.3% of the gene expression variation across continents. This study provides a rare qualitative and quantitative documentation of the relative role of genomic, DNA methylation and their interaction in shaping patterns of convergent gene expression during the process of ecological speciation.

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Disordered chromatin packing regulates phenotypic plasticity

Science Advances ◽

10.1126/sciadv.aax6232 ◽

2020 ◽

Vol 6 (2) ◽

pp. eaax6232 ◽

Cited By ~ 4

Author(s):

Ranya K. A. Virk ◽

Wenli Wu ◽

Luay M. Almassalha ◽

Greta M. Bauer ◽

Yue Li ◽

...

Keyword(s):

Gene Expression ◽

Phenotypic Plasticity ◽

Molecular Diffusion ◽

Three Dimensional ◽

Physical Factors ◽

Binding Affinities ◽

Model Predictions ◽

Chromatin Packing ◽

Chromatin Density

Three-dimensional supranucleosomal chromatin packing plays a profound role in modulating gene expression by regulating transcription reactions through mechanisms such as gene accessibility, binding affinities, and molecular diffusion. Here, we use a computational model that integrates disordered chromatin packing (CP) with local macromolecular crowding (MC) to study how physical factors, including chromatin density, the scaling of chromatin packing, and the size of chromatin packing domains, influence gene expression. We computationally and experimentally identify a major role of these physical factors, specifically chromatin packing scaling, in regulating phenotypic plasticity, determining responsiveness to external stressors by influencing both intercellular transcriptional malleability and heterogeneity. Applying CPMC model predictions to transcriptional data from cancer patients, we identify an inverse relationship between patient survival and phenotypic plasticity of tumor cells.

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The role of epigenetic regulation in adaptive phenotypic plasticity of plants

Ukrainian Botanical Journal ◽

10.15407/ukrbotj78.05.347 ◽

2021 ◽

Vol 78 (5) ◽

pp. 347-359

Author(s):

E.L. Kordyum ◽

◽

D.V. Dubyna ◽

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Phenotypic Plasticity ◽

Epigenetic Regulation ◽

Molecular Mechanisms ◽

Regulation Of Gene Expression ◽

Model Species ◽

Wide Range ◽

Adaptive Phenotypic Plasticity

In recent decades, knowledge about the role of epigenetic regulation of gene expression in plant responses to external stimuli and in adaptation of plants to adverse environmental fluctuations have extended significantly. DNA methylation is considered as the main molecular mechanism that provides genomic information and contributes to the understanding of the molecular basis of phenotypic variations based on epigenetic modifications. Unfortunately, the vast majority of research in this area has been performed on the model species Arabidopsis thaliana. The development of the methylation-sensitive amplified polymorphism (MSAP) method has made it possible to implement the large-scale detection of DNA methylation alterations in wild non-model and agricultural plants with large and highly repetitive genomes in natural and manipulated habitats. The article presents current information on DNA methylation in species of natural communities and crops and its importance in plant development and adaptive phenotypic plasticity, along with brief reviews of current ideas about adaptive phenotypic plasticity and epigenetic regulation of gene expression. The great potential of further studies of the epigenetic role in phenotypic plasticity of a wide range of non-model species in natural populations and agrocenoses for understanding the molecular mechanisms of plant existence in the changing environment in onto- and phylogeny, directly related to the key tasks of forecasting the effects of global warming and crop selection, is emphasized. Specific taxa of the Ukrainian flora, which, in authors’ opinion, are promising and interesting for this type of research, are recommended.

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The importance of alternative splicing in adaptive evolution

10.32942/osf.io/wak9g ◽

2021 ◽

Author(s):

Pooja Singh ◽

Ehsan Pashay Ahi

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Adaptive Evolution ◽

Adaptive Divergence ◽

Mrna Isoforms ◽

Evolutionary Transitions ◽

Splice Variation ◽

Gene Regulatory ◽

Splice Forms

Although alternative splicing is a ubiquitous gene regulatory mechanism in plants and animals, its contribution to evolutionary transitions is understudied. Splicing enables different mRNA isoforms to be generated from the same gene, expanding transcriptomic and proteomic diversity. While the role of gene expression in adaptive evolution is widely accepted, biologists still debate the functional impact of alternative isoforms on phenotype. In light of recent empirical research linking splice variation to ecological adaptations, we propose that alternative splicing is an important substrate for adaptive evolution and speciation, particularly at short timescales. We synthesise what is known about the role of splicing in adaptive evolution. We discuss the contribution of standing splice variation to phenotypic plasticity and how hybridisation can produce novel splice forms. Going forwards, we propose that splicing be included as a standard analysis alongside gene expression analysis so we can better understand of how splicing contributes to adaptive divergence at the micro- and macroevolutionary levels.

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Conserved patterns of alternative splicing in response to cold acclimation in fish

10.1101/429704 ◽

2018 ◽

Cited By ~ 1

Author(s):

Timothy M. Healy ◽

Patricia M. Schulte

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Phenotypic Plasticity ◽

Cold Acclimation ◽

Gasterosteus Aculeatus ◽

Expression Patterns ◽

Functional Enrichment ◽

Cold Temperatures ◽

Qualitative Changes

AbstractPhenotypic plasticity is an important aspect of an organism’s response to environmental change that often requires the modulation of gene expression. These changes in gene expression can be quantitative as a result of increases or decreases in the amounts of specific transcripts, or qualitative as a result of the expression of alternative transcripts from the same gene (e.g., via alternative splicing of pre-mRNAs). Although the role of quantitative changes in gene expression in phenotypic plasticity is well known, relatively few studies have examined the role of qualitative changes. Here, we use skeletal muscle RNA-seq data from Atlantic killifish (Fundulus heteroclitus), threespine stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio) to investigate the extent of qualitative changes in gene expression in response to cold. Fewer genes demonstrated alternative splicing than differential expression as a result of cold acclimation; however, differences in splicing were detected for between 426 and 866 genes depending on species, indicating that large numbers of qualitative changes in gene expression are associated with cold acclimation. Many of these alternatively spliced genes were also differentially expressed, and there was functional enrichment for involvement in muscle contraction among the genes demonstrating qualitative changes in response to cold acclimation. Additionally, there was a common group of 29 genes with cold-acclimation-mediated changes in splicing in all three species, suggesting that there may be a conserved set of genes with expression patterns that respond qualitatively to prolonged cold temperatures across fishes.Summary statementQualitative changes in gene expression, such as those mediated by alternative splicing of mRNAs, are involved in phenotypic plasticity in response to prolonged cold acclimation in ectothermic animals

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Role of small nuclear RNAs in eukaryotic gene expression

Essays in Biochemistry ◽

10.1042/bse0540079 ◽

2013 ◽

Vol 54 ◽

pp. 79-90 ◽

Cited By ~ 34

Author(s):

Saba Valadkhan ◽

Lalith S. Gunawardane

Keyword(s):

Gene Expression ◽

Protein Interactions ◽

Rna Stability ◽

Splice Sites ◽

Branch Site ◽

Small Nuclear Rnas ◽

Eukaryotic Gene Expression ◽

Eukaryotic Gene ◽

Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

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