Ecological speciation promoted by divergent regulation of functional genes within African cichlid fishes

2022 ◽  
Author(s):  
Madeleine Carruthers ◽  
Duncan E Edgley ◽  
Andrew D Saxon ◽  
Nestory P Gabagambi ◽  
Asilatu Shechonge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Adaptive Immune System ◽  
Ecological Speciation ◽  
System Response ◽  
East African ◽  
Significant Differential Expression ◽  
Adaptive Diversification ◽  
Regulatory Variants

Rapid ecological speciation along depth gradients has taken place independently and repeatedly in freshwater fishes. While the extent of genomic divergence between ecomorphs is often well understood, the molecular mechanisms facilitating such rapid diversification are typically unclear. In Lake Masoko, an East African crater lake, the cichlid Astatotilapia calliptera has diverged into shallow littoral and deep benthic ecomorphs with strikingly different jaw structures within the last 1,000 years. Using genome-wide transcriptome data from jaw tissue, we explore two major regulatory transcriptional mechanisms, expression and splicing QTL variants and examine their contribution to differential gene expression underpinning functional phenotypes. We identified 7,550 genes with significant differential expression between ecomorphs, of which 4.2% were regulated by cis-regulatory expression QTLs, and 6.4% were regulated by cis-regulatory splicing QTLs. There were also strong signals of divergent selection of differentially expressed genes that showed divergent regulation from expression, splicing or both QTL variants, including genes associated with major jaw plasticity and adaptation networks, adaptive immune system response, and oxidoreductase processes. These results suggest that transcriptome plasticity and modification have important roles during early-stage ecological speciation and demonstrate the role of regulatory-variants as important targets of selection driving ecologically-relevant divergence in gene expression that is associated with adaptive diversification.

scholarly journals Mechanically Sensitive HSF1 is a Key Regulator of Left-Right Symmetry Breaking in Zebrafish Embryos

2021 ◽  
Author(s):  
Jing Du ◽  
Shu-Kai Li ◽  
Liu-Yuan Guan ◽  
Zheng Guo ◽  
Jiang-Fan Yin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Symmetry Breaking ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Gene Expression Regulation ◽  
Early Stage ◽  
Expression Regulation ◽  
Zebrafish Embryos ◽  
Mechanical Stimuli ◽  
Nodal Flow

AbstractThe left-right symmetry breaking of vertebrate embryos requires fluid flow (called nodal flow in zebrafish). However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. In this paper, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kuppfer’s vesicle at the early stage of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 could be immediately activated by fluid shear stress. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and the Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation triggered by mechanical clues during embryonic development and other physiological and pathological transformations.

scholarly journals Reprogramming of the Wheat Transcriptome in Response to Infection with Claviceps Purpurea, the Causal Agent of Ergot

2020 ◽  
Author(s):  
Lesley A. Boyd ◽  
Eleni Tente ◽  
Nelzo Ereful ◽  
Anyela Camargo Rodriguez ◽  
Paul Grant ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Early Stage ◽  
Receptor Protein ◽  
Claviceps Purpurea ◽  
Long Distance ◽  
Transmitting Tissue ◽  
Significant Differential Expression ◽  
Differential Gene ◽  
Wheat Transcriptome

Abstract Background: Ergot, caused by the fungal pathogen Claviceps purpurea, infects the female flowers of a range of cereal crops, including wheat. To understand the interaction between C. purpurea and hexaploid wheat we undertook an extensive examination of the reprogramming of the wheat transcriptome in response to C. purpurea infection through floral tissues (i.e. the stigma, transmitting and base ovule tissues of the ovary) and over time. Results: C. purpurea hyphae were observed to have grown into and down the stigma at 24 hours (H) after inoculation. By 48H hyphae had grown through the transmitting tissue into the base, while by 72H hyphae had surrounded the ovule. By 5 days (D) the ovule had been replaced by fungal tissue. Significant differential gene expression was first observed at 1H in the stigma tissue. Many of the wheat genes differentially transcribed in response to C. purpurea infection were associated with plant hormones and included the ethylene (ET), auxin, cytokinin, gibberellic acid (GA), salicylic acid and jasmonic acid (JA) biosynthetic and signaling pathways. Hormone-associated genes were first detected in the stigma and base tissues at 24H, but not in the transmitting tissue. Genes associated with GA and JA pathways were seen in the stigma at 24H, while JA and ET-associated genes were identified in the base at 24H. In addition, several defence-associated genes were differential expressed in response to C. purpurea infection, including antifungal proteins, endocytosis/exocytosis-related proteins, NBS-LRR class proteins, genes involved in programmed cell death, receptor protein kinases and transcription factors. Of particular interest was the identification of significant differential expression of wheat genes in the base tissue well before the appearance of fungal hyphae, suggesting that a mobile signal, either pathogen or plant-derived, is delivered to the base prior to colonisation.Conclusions: Multiple host hormonal biosynthesis and signalling pathways were significantly perturbed from an early stage in the wheat – C. purpurea interaction. Significant differential gene expression at the base of the ovary, ahead of arrival of the pathogen, indicated the potential presence of a long-distance signal modifying host gene expression.

Abstract 17064: Enrichment of Cardiotoxic Gene Expression Profile in Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes in Response to Tyrosine Kinase Inhibitor Nilotinib

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Praful Aggarwal ◽  
Matthew White ◽  
Andrea Matter ◽  
Amy Turner ◽  
Benjamin Olson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tyrosine Kinase ◽  
Gene Expression Profile ◽  
Cell Lines ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
P Value ◽  
Significant Differential Expression ◽  
Cell Index ◽  
Beat Rate

Small molecule tyrosine kinase inhibitors (TKIs) are a valuable class of therapeutics with widespread clinical utility against multiple cancers. However, there is strong evidence that TKIs are associated with cardiotoxicity and adverse cardiovascular events. Our understanding of the underlying mechanisms related to TKI induced cardiotoxicity is limited. Human iPSC derived cardiomyocytes (hiPSC-CMs) provide a flexible platform and unique model to study the underlying molecular mechanisms associated with TKI associated cardiotoxicity. In this study we describe the gene expression profile between hiPSC-CM cell lines which exhibit susceptibility vs. resistance. RNA-seq analysis was performed in hiPSC-CM cell lines from six participants in the NHLBI HyperGEN study (A to F). Experiments were performed in triplicate using sunitinib (SUN), vandetanib (VAN), gefitinib (GEF) and nilotinib (NIL). We analyzed beat rate, cell index and ATP viability as physiological measurements of CM toxicity and defined a 20% change from the normalized control as TKI susceptibility. Differential gene expression analysis was performed using DESeq2. We observed significant physiological differences between the different hiPSC-CMs after TKI treatment (beat rate, cell index and ATP viability). The most variable cell index and beat rate response was observed for NIL. Based on cell index, lines B, D, E were resistant while A, C, F were significantly more susceptible to NIL. Principal component analysis showed that the variance in gene expression was the highest after NIL treatment when compared to controls (16% for NIL; 11% for VAN; 6% for SUN and 5% for GEF). A total of 567 genes exhibited significant differential expression changes (adj. p-value ≤ 0.1) after NIL treatment in susceptible versus resistant lines. Pathway analysis showed significant enrichment for cardiotoxicity including pathways implicated in cardiac infarction, fibrosis, hypertrophy, and congestive cardiac failure. Taken together, our results identify unique gene expression changes associated with TKI cardiotoxicity. Furthermore, the variability in TKI susceptibility between different hiPSC-CM lines highlights the need to comprehensively assess cardiotoxicity in a diverse set of lines on a physiological and molecular level.

scholarly journals Comprehensive analysis of gene expression in human retina and supporting tissues

2014 ◽  
Vol 23 (15) ◽  
pp. 4001-4014 ◽  
Author(s):  
Mingyao Li ◽  
Cheng Jia ◽  
Krista L. Kazmierkiewicz ◽  
Anita S. Bowman ◽  
Lifeng Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Phenotypic Diversity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Posterior Part ◽  
Age Related Macular Degeneration ◽  
Human Retina ◽  
Significant Differential Expression ◽  
Age Related

Understanding the influence of gene expression on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. We have carried out whole transcriptome expression analysis on a series of eight normal human postmortem eyes by RNA sequencing. Here we present data showing that ∼80% of the transcriptome is expressed in the posterior layers of the eye and that there is significant differential expression not only between the layers of the posterior part of the eye but also between locations of a tissue layer. These differences in expression also extend to alternative splicing and splicing factors. Differentially expressed genes are enriched for genes associated with psychiatric, immune and cardiovascular disorders. Enrichment categories for gene ontology included ion transport, synaptic transmission and visual and sensory perception. Lastly, allele-specific expression was found to be significant forCFH,C3 andCFB, which are known risk genes for age-related macular degeneration. These expression differences should be useful in determining the underlying biology of associations with common diseases of the human retina, retinal pigment epithelium and choroid and in guiding the analysis of the genomic regions involved in the control of normal gene expression.

scholarly journals Shared genetic effects on chromatin and gene expression reveal widespread enhancer priming in immune response

2017 ◽  
Author(s):  
Kaur Alasoo ◽  
Julia Rodrigues ◽  
Subhankar Mukhopadhyay ◽  
Andrew J. Knights ◽  
Alice L. Mann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Large Fraction ◽  
Chromatin Accessibility ◽  
Genetic Effects ◽  
Small Subset ◽  
Regulatory Variants ◽  
Large Numbers ◽  
Cell Type Specific ◽  
Context Specific

AbstractNoncoding regulatory variants are often highly context-specific, modulating gene expression in a small subset of possible cellular states. Although these genetic effects are likely to play important roles in disease, the molecular mechanisms underlying context-specificity are not well understood. Here, we identify shared quantitative trait loci (QTLs) for chromatin accessibility and gene expression (eQTLs) and show that a large fraction (∼60%) of eQTLs that appear following macrophage immune stimulation alter chromatin accessibility in unstimulated cells, suggesting they perturb enhancer priming. We show that such variants are likely to influence the binding of cell type specific transcription factors (TFs), such as PU.1, which then indirectly alter the binding of stimulus-specific TFs, such as NF-κB or STAT2. Our results imply that, although chromatin accessibility assays are powerful for fine mapping causal noncoding variants, detecting their downstream impact on gene expression will be challenging, requiring profiling of large numbers of stimulated cellular states and timepoints.

scholarly journals A comprehensive catalogue of regulatory variants in the cattle transcriptome

2020 ◽  
Author(s):  
Shuli Liu ◽  
Yahui Gao ◽  
Oriol Canela-Xandri ◽  
Sheng Wang ◽  
Ying Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Agronomic Traits ◽  
Economic Value ◽  
Tissue Expression ◽  
Genetic Associations ◽  
Rna Sequences ◽  
Regulatory Variants ◽  
Expression Atlas ◽  
Regulatory Effects

AbstractCharacterization of genetic regulatory variants acting on the transcriptome of livestock is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here, we build a cattle Genotype-Tissue Expression atlas (cGTEx, http://cgtex.roslin.ed.ac.uk/) for the research community based on 11,642 RNA sequences from publicly available datasets representing over 100 cattle tissues. We describe the landscape of the transcriptome across tissues and report hundreds of thousands of cis- and trans- genetic associations with gene expression and alternative splicing for 24 major tissues. We evaluate the specificity/similarity of these genetic regulatory effects across tissues, and functionally annotate them using a combination of multi-omics data. Finally, we link gene expression in different tissues to 43 economically important traits using a large transcriptome-wide association study (TWAS) to provide novel biological insights into the molecular regulatory mechanisms underpinning agronomic traits in cattle.

scholarly journals Transcriptomic Analysis of Changes in Gene Expression During Flowering Induction in Sugarcane Under Controlled Photoperiodic Conditions

2021 ◽  
Vol 12 ◽  
Author(s):  
João Ricardo Vieira Manechini ◽  
Paulo Henrique da Silva Santos ◽  
Elisson Romanel ◽  
Michael dos Santos Brito ◽  
Maximiliano Salles Scarpari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
System Development ◽  
Expression Patterns ◽  
Group Analysis ◽  
Lignin Biosynthesis ◽  
Enrichment Analysis ◽  
Vegetative Development ◽  
Sugarcane Cultivar

Flowering is of utmost relevance for the agricultural productivity of the sugarcane bioeconomy, but data and knowledge of the genetic mechanisms underlying its photoperiodic induction are still scarce. An understanding of the molecular mechanisms that regulate the transition from vegetative to reproductive growth in sugarcane could provide better control of flowering for breeding. This study aimed to investigate the transcriptome of +1 mature leaves of a sugarcane cultivar subjected to florally inductive and non-inductive photoperiodic treatments to identify gene expression patterns and molecular regulatory modules. We identified 7,083 differentially expressed (DE) genes, of which 5,623 showed significant identity to other plant genes. Functional group analysis showed differential regulation of important metabolic pathways involved in plant development, such as plant hormones (i.e., cytokinin, gibberellin, and abscisic acid), light reactions, and photorespiration. Gene ontology enrichment analysis revealed evidence of upregulated processes and functions related to the response to abiotic stress, photoprotection, photosynthesis, light harvesting, and pigment biosynthesis, whereas important categories related to growth and vegetative development of plants, such as plant organ morphogenesis, shoot system development, macromolecule metabolic process, and lignin biosynthesis, were downregulated. Also, out of 76 sugarcane transcripts considered putative orthologs to flowering genes from other plants (such as Arabidopsis thaliana, Oryza sativa, and Sorghum bicolor), 21 transcripts were DE. Nine DE genes related to flowering and response to photoperiod were analyzed either at mature or spindle leaves at two development stages corresponding to the early stage of induction and inflorescence primordia formation. Finally, we report a set of flowering-induced long non-coding RNAs and describe their level of conservation to other crops, many of which showed expression patterns correlated against those in the functionally grouped gene network.

scholarly journals Blood and brain gene expression trajectories mirror neuropathology and clinical deterioration in neurodegeneration

Brain ◽  
2020 ◽  
Vol 143 (2) ◽  
pp. 661-673 ◽  
Author(s):  
Yasser Iturria-Medina ◽  
Ahmed F Khan ◽  
Quadri Adewale ◽  
Amir H Shirazi ◽  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Learning Algorithm ◽  
Late Onset ◽  
Clinical Deterioration ◽  
System Response ◽  
Molecular Pathways ◽  
Disease Evolution ◽  
Promising Tool

Abstract Most prevalent neurodegenerative disorders take decades to develop and their early detection is challenged by confounding non-pathological ageing processes. For all neurodegenerative conditions, we continue to lack longitudinal gene expression data covering their large temporal evolution, which hinders the understanding of the underlying dynamic molecular mechanisms. Here, we overcome this key limitation by introducing a novel gene expression contrastive trajectory inference (GE-cTI) method that reveals enriched temporal patterns in a diseased population. Evaluated on 1969 subjects in the spectrum of late-onset Alzheimer’s and Huntington’s diseases (from ROSMAP, HBTRC and ADNI datasets), this unsupervised machine learning algorithm strongly predicts neuropathological severity (e.g. Braak, amyloid and Vonsattel stages). Furthermore, when applied to in vivo blood samples at baseline (ADNI), it significantly predicts clinical deterioration and conversion to advanced disease stages, supporting the identification of a minimally invasive (blood-based) tool for early clinical screening. This technique also allows the discovery of genes and molecular pathways, in both peripheral and brain tissues, that are highly predictive of disease evolution. Eighty-five to ninety per cent of the most predictive molecular pathways identified in the brain are also top predictors in the blood. These pathways support the importance of studying the peripheral-brain axis, providing further evidence for a key role of vascular structure/functioning and immune system response. The GE-cTI is a promising tool for revealing complex neuropathological mechanisms, with direct implications for implementing personalized dynamic treatments in neurology.

scholarly journals Robust Sampling of Defective Pathways in Multiple Myeloma

2019 ◽  
Vol 20 (19) ◽  
pp. 4681 ◽  
Author(s):  
Juan Luis Fernández-Martínez ◽  
Enrique J. de Andrés-Galiana ◽  
Francisco Javier Fernández-Ovies ◽  
Ana Cernea ◽  
Andrzej Kloczkowski
Keyword(s):  
Gene Expression ◽  
Infectious Disease ◽  
Multiple Myeloma ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
System Response ◽  
Genetic Pathways ◽  
Immune System Response ◽  
The Difference

We present the analysis of defective pathways in multiple myeloma (MM) using two recently developed sampling algorithms of the biological pathways: The Fisher’s ratio sampler, and the holdout sampler. We performed the retrospective analyses of different gene expression datasets concerning different aspects of the disease, such as the existing difference between bone marrow stromal cells in MM and healthy controls (HC), the gene expression profiling of CD34+ cells in MM and HC, the difference between hyperdiploid and non-hyperdiploid myelomas, and the prediction of the chromosome 13 deletion, to provide a deeper insight into the molecular mechanisms involved in the disease. Our analysis has shown the importance of different altered pathways related to glycosylation, infectious disease, immune system response, different aspects of metabolism, DNA repair, protein recycling and regulation of the transcription of genes involved in the differentiation of myeloid cells. The main difference in genetic pathways between hyperdiploid and non-hyperdiploid myelomas are related to infectious disease, immune system response and protein recycling. Our work provides new insights on the genetic pathways involved in this complex disease and proposes novel targets for future therapies.

scholarly journals Impact of the X chromosome and sex on regulatory variation

2015 ◽  
Author(s):  
Kimberly R Kukurba ◽  
Princy Parsana ◽  
Kevin S Smith ◽  
Zachary Zappala ◽  
David A Knowles ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Specific Gene ◽  
Specific Expression ◽  
Regulatory Variation ◽  
Regulatory Variants ◽  
Genome Wide ◽  
The Impact

The X chromosome, with its unique mode of inheritance, contributes to differences between the sexes at a molecular level, including sex-specific gene expression and sex-specific impact of genetic variation. We have conducted an analysis of the impact of both sex and the X chromosome on patterns of gene expression identified through transcriptome sequencing of whole blood from 922 individuals. We identified that genes on the X chromosome are more likely to have sex-specific expression compared to the autosomal genes. Furthermore, we identified a depletion of regulatory variants on the X chromosome, especially among genes under high selective constraint. In contrast, we discovered an enrichment of sex-specific regulatory variants on the X chromosome. To resolve the molecular mechanisms underlying such effects, we generated and connected sex-specific chromatin accessibility to sex-specific expression and regulatory variation. As sex-specific regulatory variants can inform sex differences in genetic disease prevalence, we have integrated our data with genome-wide association study data for multiple immune traits and to identify traits with significant sex biases. Together, our study provides genome-wide insight into how the X chromosome and sex shape human gene regulation and disease.

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