scholarly journals Gene Regulatory Evolution During Speciation in a Songbird

2015 ◽  
Author(s):  
Christopher N. Balakrishnan ◽  
John H. Davidson
Keyword(s):  
High Rate ◽  
F1 Hybrids ◽  
Rna Seq ◽  
Comprehensive Understanding ◽  
Regulatory Evolution ◽  
Tremendous Progress ◽  
Postzygotic Reproductive Isolation ◽  
Gene Regulatory ◽  
Slow Evolution ◽  
In Cis

Over the last decade tremendous progress has been made towards a comparative understanding of gene regulatory evolution. However, we know little about how gene regulation evolves in birds, and how divergent genomes interact in their hybrids. Because of unique features of birds - female heterogamety, a highly conserved karyotype, and the slow evolution of reproductive incompatibilities - an understanding of regulatory evolution in birds is critical to a comprehensive understanding of regulatory evolution and its implications for speciation. Using a novel complement of analyses of replicated RNA-seq libraries, we demonstrate abundant divergence in gene expression between subspecies of zebra finches Taeniopygia guttata. By comparing parental populations and their F1 hybrids, we also show that gene misexpression is relatively rare, a pattern that may partially explain the slow buildup of postzygotic reproductive isolation observed in birds relative to other taxa. Although we expected that the action of genetic drift on the island-dwelling zebra finch subspecies would be manifested in a high rate of trans regulatory divergence, we found that most divergence was in cis regulation, following a pattern commonly observed in other taxa. Thus our study highlights both unique and shared features of avian regulatory evolution.

scholarly journals Contributions of cis- and trans-Regulatory Evolution to Transcriptomic Divergence across Populations in the Drosophila mojavensis Larval Brain

2020 ◽  
Vol 12 (8) ◽  
pp. 1407-1418
Author(s):  
Kyle M Benowitz ◽  
Joshua M Coleman ◽  
Carson W Allan ◽  
Luciano M Matzkin
Keyword(s):  
Gene Expression ◽  
Population Level ◽  
F1 Hybrids ◽  
Evolutionary Divergence ◽  
Drosophila Mojavensis ◽  
Regulatory Evolution ◽  
Larval Brain ◽  
Expression Evolution ◽  
Trans Regulation ◽  
In Cis

Abstract Natural selection on gene expression was originally predicted to result primarily in cis- rather than trans-regulatory evolution, due to the expectation of reduced pleiotropy. Despite this, numerous studies have ascribed recent evolutionary divergence in gene expression predominantly to trans-regulation. Performing RNA-seq on single isofemale lines from genetically distinct populations of the cactophilic fly Drosophila mojavensis and their F1 hybrids, we recapitulated this pattern in both larval brains and whole bodies. However, we demonstrate that improving the measurement of brain expression divergence between populations by using seven additional genotypes considerably reduces the estimate of trans-regulatory contributions to expression evolution. We argue that the finding of trans-regulatory predominance can result from biases due to environmental variation in expression or other sources of noise, and that cis-regulation is likely a greater contributor to transcriptional evolution across D. mojavensis populations. Lastly, we merge these lines of data to identify several previously hypothesized and intriguing novel candidate genes, and suggest that the integration of regulatory and population-level transcriptomic data can provide useful filters for the identification of potentially adaptive genes.

scholarly journals Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bharat Mishra ◽  
Mohammad Athar ◽  
M. Shahid Mukhtar
Keyword(s):  
Immune Responses ◽  
Gene Regulatory Networks ◽  
Racial Disparity ◽  
Regulatory Networks ◽  
Target Genes ◽  
Decisive Role ◽  
Rna Seq ◽  
Comprehensive Understanding ◽  
Regulatory Behavior ◽  
Gene Regulatory

AbstractMacrophages are ubiquitous custodians of tissues, which play decisive role in maintaining cellular homeostasis through regulatory immune responses. Within tissues, macrophage exhibit extremely heterogeneous population with varying functions orchestrated through regulatory response, which can be further exacerbated in diverse genetic backgrounds. Gene regulatory networks (GRNs) offer comprehensive understanding of cellular regulatory behavior by unfolding the transcription factors (TFs) and regulated target genes. RNA-Seq coupled with ATAC-Seq has revolutionized the regulome landscape influenced by gene expression modeling. Here, we employ an integrative multi-omics systems biology-based analysis and generated GRNs derived from the unstimulated bone marrow-derived macrophages of five inbred genetically defined murine strains, which are reported to be linked with most of the population-wide human genetic variants. Our probabilistic modeling of a basal hemostasis pan regulatory repertoire in diverse macrophages discovered 96 TFs targeting 6279 genes representing 468,291 interactions across five inbred murine strains. Subsequently, we identify core and distinctive GRN sub-networks in unstimulated macrophages to describe the system-wide conservation and dissimilarities, respectively across five murine strains. Our study concludes that discrepancies in unstimulated macrophage-specific regulatory networks not only drives the basal functional plasticity within genetic backgrounds, additionally aid in understanding the complexity of racial disparity among the human population during stress.

scholarly journals Inferring gene regulatory networks from single-cell RNA-seq temporal snapshot data requires higher-order moments

Patterns ◽  
2021 ◽  
Vol 2 (9) ◽  
pp. 100332
Author(s):  
N. Alexia Raharinirina ◽  
Felix Peppert ◽  
Max von Kleist ◽  
Christof Schütte ◽  
Vikram Sunkara
Keyword(s):  
Single Cell ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Higher Order ◽  
Rna Seq ◽  
Higher Order Moments ◽  
Gene Regulatory

scholarly journals Somatic Cell Nuclear Transfer Embryos Show Massive Dysregulation of Genes Involved in Transcription Pathway

2020 ◽  
Author(s):  
Chunshen Long ◽  
Hanshuang Li ◽  
Xinru Li ◽  
Yongchun Zuo
Keyword(s):  
Embryo Development ◽  
Nuclear Transfer ◽  
Normal Embryo ◽  
Cloning Efficiency ◽  
Rna Seq ◽  
Activation Of Transcription ◽  
Potential Association ◽  
Gene Regulatory ◽  
Genome Activation ◽  
Zygotic Genome

AbstractTranscription is the most fundamental molecular event that occurs with zygotic genome activation (ZGA) during embryo development. However, the potential association between transcription pathways and low cloning efficiency of nuclear transfer (NT) embryos remains elusive. Here, we integrated a series of RNA-seq data on NT embryos to deciphering the molecular barriers of NT embryo development. Comparative transcriptome analysis indicated that incomplete activation of transcription pathways functions as a barrier for NT embryos. Then, the gene regulatory network (GRN) identified that crucial factors responsible for transcription play a coordinated role in epigenome erasure and pluripotency regulation during normal embryo development. But in NT embryos, massive genes involved in transcription pathways were varying degrees of inhibition. Our study therefore provides new insights into understanding the barriers to NT embryo reprogramming.

scholarly journals Tissue-specific cis-regulatory divergence implicates a fatty acid elongase necessary for inhibiting interspecies mating in Drosophila

2018 ◽  
Author(s):  
Peter A. Combs ◽  
Joshua J. Krupp ◽  
Neil M. Khosla ◽  
Dennis Bua ◽  
Dmitri A. Petrov ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Candidate Genes ◽  
Molecular Mechanisms ◽  
Sister Species ◽  
F1 Hybrids ◽  
Rna Seq ◽  
Fatty Acid Elongase ◽  
Tissue Specific ◽  
Regulatory Changes ◽  
Wide Range

AbstractPheromones known as cuticular hydrocarbons are a major component of reproductive isolation in Drosophila. Individuals from morphologically similar sister species produce different sets of hydrocarbons that allow potential mates to identify them as a suitable partner. In order to explore the molecular mechanisms underlying speciation, we performed RNA-seq in F1 hybrids to measure tissue-specific cis-regulatory divergence between the sister species D. simulans and D. sechellia. By focusing on cis-regulatory changes specific to female oenocytes, we rapidly identified a small number of candidate genes. We found that one of these, the fatty acid elongase eloF, broadly affects both the complement of hydrocarbons present on D. sechellia females and the propensity of D. simulans males to mate with those females. In addition, knockdown of eloF in the more distantly related D. melanogaster led to a similar shift in hydrocarbons as well as lower interspecific mate discrimination by D. simulans males. Thus, cis-regulatory changes in eloF appear to be a major driver in the sexual isolation of D. simulans from multiple other species. More generally, our RNA-seq approach proved to be far more efficient than QTL mapping in identifying candidate genes; the same framework can be used to pinpoint cis-regulatory drivers of divergence in a wide range of traits differing between any interfertile species.

scholarly journals Uncovering the mesendoderm gene regulatory network through multi-omic data integration

2020 ◽  
Author(s):  
Camden Jansen ◽  
Kitt D. Paraiso ◽  
Jeff J. Zhou ◽  
Ira L. Blitz ◽  
Margaret B. Fish ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cell Fate ◽  
Data Sets ◽  
List Type ◽  
Rna Seq ◽  
Data Types ◽  
Cell Fate Decisions ◽  
Gene Regulatory ◽  
Genome Scale ◽  
Omic Data

SummaryMesendodermal specification is one of the earliest events in embryogenesis, where cells first acquire distinct identities. Cell differentiation is a highly regulated process that involves the function of numerous transcription factors (TFs) and signaling molecules, which can be described with gene regulatory networks (GRNs). Cell differentiation GRNs are difficult to build because existing mechanistic methods are low-throughput, and high-throughput methods tend to be non-mechanistic. Additionally, integrating highly dimensional data comprised of more than two data types is challenging. Here, we use linked self-organizing maps to combine ChIP-seq/ATAC-seq with temporal, spatial and perturbation RNA-seq data from Xenopus tropicalis mesendoderm development to build a high resolution genome scale mechanistic GRN. We recovered both known and previously unsuspected TF-DNA/TF-TF interactions and validated through reporter assays. Our analysis provides new insights into transcriptional regulation of early cell fate decisions and provides a general approach to building GRNs using highly-dimensional multi-omic data sets.HighlightsBuilt a generally applicable pipeline to creating GRNs using highly-dimensional multi-omic data setsPredicted new TF-DNA/TF-TF interactions during mesendoderm developmentGenerate the first genome scale GRN for vertebrate mesendoderm and expanded the core mesendodermal developmental network with high fidelityDeveloped a resource to visualize hundreds of RNA-seq and ChIP-seq data using 2D SOM metaclusters.

scholarly journals Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shoujun Gu ◽  
Rafal Olszewski ◽  
Ian Taukulis ◽  
Zheng Wei ◽  
Daniel Martin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Adult Mouse ◽  
Stria Vascularis ◽  
Cell Types ◽  
Rna Seq ◽  
Root Cells ◽  
Transcriptional Profiles ◽  
Gene Regulatory

Abstract The stria vascularis (SV) in the cochlea generates and maintains the endocochlear potential, thereby playing a pivotal role in normal hearing. Knowing transcriptional profiles and gene regulatory networks of SV cell types establishes a basis for studying the mechanism underlying SV-related hearing loss. While we have previously characterized the expression profiles of major SV cell types in the adult mouse, transcriptional profiles of rare SV cell types remained elusive due to the limitation of cell capture in single-cell RNA-Seq. The role of these rare cell types in the homeostatic function of the adult SV remain largely undefined. In this study, we performed single-nucleus RNA-Seq on the adult mouse SV in conjunction with sample preservation treatments during the isolation steps. We distinguish rare SV cell types, including spindle cells and root cells, from other cell types, and characterize their transcriptional profiles. Furthermore, we also identify and validate novel specific markers for these rare SV cell types. Finally, we identify homeostatic gene regulatory networks within spindle and root cells, establishing a basis for understanding the functional roles of these cells in hearing. These novel findings will provide new insights for future work in SV-related hearing loss and hearing fluctuation.

scholarly journals COL2A1 Is a Novel Biomarker of Melanoma Tumor Repopulating Cells

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 360
Author(s):  
Bhavana Talluri ◽  
Kshitij Amar ◽  
Michael Saul ◽  
Tasnim Shireen ◽  
Vjollca Konjufca ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Line ◽  
Aerobic Glycolysis ◽  
Parental Control ◽  
Control Cell ◽  
Differentially Expressed Gene ◽  
Gene Clusters ◽  
Rna Seq ◽  
Novel Biomarkers ◽  
Gene Regulatory

Soft 3D-fibrin-gel selected tumor repopulating cells (TRCs) from the B16F1 melanoma cell line exhibit extraordinary self-renewal and tumor-regeneration capabilities. However, their biomarkers and gene regulatory features remain largely unknown. Here, we utilized the next-generation sequencing-based RNA sequencing (RNA-seq) technique to discover novel biomarkers and active gene regulatory features of TRCs. Systems biology analysis of RNA-seq data identified differentially expressed gene clusters, including the cell adhesion cluster, which subsequently identified highly specific and novel biomarkers, such as Col2a1, Ncam1, F11r, and Negr1. We validated the expression of these genes by real-time qPCR. The expression level of Col2a1 was found to be relatively low in TRCs but twenty-fold higher compared to the parental control cell line, thus making the biomarker very specific for TRCs. We validated the COL2A1 protein by immunofluorescence microscopy, showing a higher expression of COL2A1 in TRCs compared to parental control cells. KEGG pathway analysis showed the JAK/STAT, hypoxia, and Akt signaling pathways to be active in TRCs. Besides, the aerobic glycolysis pathway was found to be very active, indicating a typical Warburg Effect on highly tumorigenic cells. Together, our study revealed highly specific biomarkers and active cell signaling pathways of melanoma TRCs that can potentially target and neutralize TRCs.

scholarly journals Transcriptomic Analysis Reveals Hormonal Control of Shoot Branching in Salix matsudana

Forests ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 287
Author(s):  
Juanjuan Liu ◽  
Bingbing Ni ◽  
Yanfei Zeng ◽  
Caiyun He ◽  
Jianguo Zhang
Keyword(s):  
Molecular Level ◽  
Hormonal Control ◽  
Molecular Techniques ◽  
Differentially Expressed ◽  
Shoot Branching ◽  
Rna Seq ◽  
Comprehensive Understanding ◽  
Regulatory Pathways ◽  
Salix Matsudana ◽  
Transcriptome Expression

Shoot branching is regulated by axillary bud activities, which subsequently grow into branches. Phytohormones play a central role in shoot branching control, particularly with regard to auxin, cytokinins (CKs), strigolactones (SLs), and gibberellins (GAs). To further study the molecular basis for the shoot branching in Salix matsudana, how shoot branching responds to hormones and regulatory pathways was investigated, and potential genes involved in the regulation of shoot branching were identified. However, how these positive and inhibitory processes work on the molecular level remains unknown. RNA-Seq transcriptome expression analysis was used to elucidate the mechanisms underlying shoot branching. In total, 102 genes related to auxin, CKs, SLs, and GAs were differentially expressed in willow development. A majority of the potential genes associated with branching were differentially expressed at the time of shoot branching in S. matsudana, which have more number of branching. These findings are consistent with the growth and physiological results. A regulatory network model was proposed to explain the interaction between the four hormones that control shoot branching. Collectively, the results presented here contribute to a more comprehensive understanding of the hormonal effects on shoot branching in S. matsudana. In the future, these findings will help uncover the interactions among auxin, SLs, CKs, and GAs that control shoot branching in willow, which could help improve plant structures through the implementation of molecular techniques in targeted breeding.

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