scholarly journals Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution

2017 ◽  
Author(s):  
Juliana G. Roscito ◽  
Katrin Sameith ◽  
Genis Parra ◽  
Bjoern E. Langer ◽  
Andreas Petzold ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Morphological Traits ◽  
Morphological Changes ◽  
Sequence Divergence ◽  
Regulatory Elements ◽  
Genomic Changes ◽  
Genome Wide ◽  
Subterranean Mammals ◽  
And Function ◽  
Regulatory Landscape

AbstractDetecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes in cis-regulatory elements are important for morphological changes. Here, we combine genome sequencing and functional genomics with genome-wide comparative analyses to investigate the fate of regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of relevant transcription factor binding sites. Importantly, diverged regulatory elements are associated with key genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results provide the first evidence that genome-wide decay of the phenotype-specific cis-regulatory landscape is a hallmark of lost morphological traits.

scholarly journals Transcriptional Regulation of RUNX1: An Informatics Analysis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1175
Author(s):  
Amarni L. Thomas ◽  
Judith Marsman ◽  
Jisha Antony ◽  
William Schierding ◽  
Justin M. O’Sullivan ◽  
...  
Keyword(s):  
Association Studies ◽  
Regulatory Elements ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Runx1 Gene ◽  
Gene Regulatory Elements ◽  
Important Regulator ◽  
Aml1 Gene ◽  
Regulatory Landscape

The RUNX1/AML1 gene encodes a developmental transcription factor that is an important regulator of haematopoiesis in vertebrates. Genetic disruptions to the RUNX1 gene are frequently associated with acute myeloid leukaemia. Gene regulatory elements (REs), such as enhancers located in non-coding DNA, are likely to be important for Runx1 transcription. Non-coding elements that modulate Runx1 expression have been investigated over several decades, but how and when these REs function remains poorly understood. Here we used bioinformatic methods and functional data to characterise the regulatory landscape of vertebrate Runx1. We identified REs that are conserved between human and mouse, many of which produce enhancer RNAs in diverse tissues. Genome-wide association studies detected single nucleotide polymorphisms in REs, some of which correlate with gene expression quantitative trait loci in tissues in which the RE is active. Our analyses also suggest that REs can be variant in haematological malignancies. In summary, our analysis identifies features of the RUNX1 regulatory landscape that are likely to be important for the regulation of this gene in normal and malignant haematopoiesis.

scholarly journals Genomic basis of striking fin shapes and colours in the fighting fish

2021 ◽  
Author(s):  
Le Wang ◽  
Fei Sun ◽  
Zi Yi Wan ◽  
Baoqing Ye ◽  
Yanfei Wen ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Association Studies ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Major Effect ◽  
Betta Splendens ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Phenotypic Variations ◽  
Genomic Basis

Abstract Resolving the genomic basis underlying phenotypic variations is a question of great importance in evolutionary biology. However, understanding how genotypes determine the phenotypes is still challenging. Centuries of artificial selective breeding for beauty and aggression resulted in a plethora of colors, long fin varieties, and hyper-aggressive behavior in the air-breathing Siamese fighting fish (Betta splendens), supplying an excellent system for studying the genomic basis of phenotypic variations. Combining whole genome sequencing, QTL mapping, genome-wide association studies and genome editing, we investigated the genomic basis of huge morphological variation in fins and striking differences in coloration in the fighting fish. Results revealed that the double tail, elephant ear, albino and fin spot mutants each were determined by single major-effect loci. The elephant ear phenotype was likely related to differential expression of a potassium ion channel gene, kcnh8. The albinotic phenotype was likely linked to a cis-regulatory element acting on the mitfa gene and the double tail mutant was suggested to be caused by a deletion in a zic1/zic4 co-enhancer. Our data highlight that major loci and cis-regulatory elements play important roles in bringing about phenotypic innovations and establish Bettas as new powerful model to study the genomic basis of evolved changes.

scholarly journals Genome-wide identification and characterization of lectin receptor-like kinase gene family in cucumber and expression profiling analysis under different treatments

2020 ◽  
Author(s):  
Duo Lv ◽  
Gang Wang ◽  
Yue Chen ◽  
Liang-Rong Xiong ◽  
Jing-Xian Sun ◽  
...  
Keyword(s):  
Gene Family ◽  
Stress Responses ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Kinase Gene ◽  
Cucumis Sativus L ◽  
Lectin Receptor ◽  
Genome Wide ◽  
Cucumber Genome ◽  
And Function

Abstract Background Lectin receptor-like kinases (LecRLKs) are a class of membrane proteins found in plants that are involved in diverse functions, including plant development and stress responses. Although LecRLK families have been identified in a variety of plants, a comprehensive analysis has not yet been undertaken in cucumber ( Cucumis sativus L.).Results In this study, 46 putative LecRLK genes were identified in cucumber genome, including 23 G-type, 22 L-type and 1 C-type LecRLK genes. They unequally distributed on all 7 chromosomes with a clustering trendency. Most of the genes in the cucumber LecRLK (Cs LecRLK) gene family lacked introns. In addition, there were many regulatory elements associated with phytohormone and stress on these genes’ promoters. Transcriptome data demonstrated that distinct expression patterns of CsLecRLK genes in various tissues. Furthermore, we found that each member of the CsLecRLK family had its own unique expression pattern under hormone and stress treatment by the quantitative real time PCR (qRT-PCR) analysis.Conclusion This study provides a better understanding of the evolution and function of LecRLK gene family in cucumber, and opens the possibility to explore the roles that LecRLK s might play in the life cycle of cucumber.

scholarly journals Single-cell ATAC-seq Signal Extraction and Enhancement with SCATE

2019 ◽  
Author(s):  
Zhicheng Ji ◽  
Weiqiang Zhou ◽  
Hongkai Ji
Keyword(s):  
Single Cell ◽  
State Of The Art ◽  
Single Cells ◽  
Regulatory Elements ◽  
Single Cell Sequencing ◽  
Statistical Framework ◽  
Genome Wide ◽  
Cell Subpopulations ◽  
Accessible Chromatin ◽  
Regulatory Landscape

AbstractSingle-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscape in single cells. Single-cell ATAC-seq data are sparse and noisy. Analyzing such data is challenging. Existing computational methods cannot accurately reconstruct activities of individual cis-regulatory elements (CREs) in individual cells or rare cell subpopulations. We present a new statistical framework, SCATE, that adaptively integrates information from co-activated CREs, similar cells, and publicly available regulome data to substantially increase the accuracy for estimating activities of individual CREs. We show that using SCATE, one can better reconstruct the regulatory landscape of a heterogeneous sample.

scholarly journals Integrative analysis of epigenetics data identifies gene-specific regulatory elements

2019 ◽  
Author(s):  
Florian Schmidt ◽  
Alexander Marx ◽  
Marie Hebel ◽  
Martin Wegner ◽  
Nina Baumgarten ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Genome Wide ◽  
A Genome ◽  
Gene Level ◽  
Regulatory Landscape ◽  
Regulatory Sites ◽  
Validation Experiments

AbstractUnderstanding the complexity of transcriptional regulation is a major goal of computational biology. Because experimental linkage of regulatory sites to genes is challenging, computational methods considering epigenomics data have been proposed to create tissue-specific regulatory maps. However, we showed that these approaches are not well suited to account for the variations of the regulatory landscape between cell-types. To overcome these drawbacks, we developed a new method called STITCHIT, that identifies and links putative regulatory sites to genes. Within STITCHIT, we consider the chromatin accessibility signal of all samples jointly to identify regions exhibiting a signal variation related to the expression of a distinct gene. STITCHIToutperforms previous approaches in various validation experiments and was used with a genome-wide CRISPR-Cas9 screen to prioritize novel doxorubicin-resistance genes and their associated non-coding regulatory regions. We believe that our work paves the way for a more refined understanding of transcriptional regulation at the gene-level.

scholarly journals Recapitulating Evolutionary Divergence in a Single Cis-Regulatory Element Is Sufficient to Cause Expression Changes of the Lens Gene Tdrd7

2020 ◽  
Author(s):  
Juliana G Roscito ◽  
Kaushikaram Subramanian ◽  
Ronald Naumann ◽  
Mihail Sarov ◽  
Anna Shevchenko ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Mrna Level ◽  
Regulatory Elements ◽  
Evolutionary Divergence ◽  
Phenotypic Differences ◽  
Evolutionary Changes ◽  
Mole Rat ◽  
Regulatory Mutations ◽  
Subterranean Mammals ◽  
And Function

Abstract Mutations in cis-regulatory elements play important roles for phenotypic changes during evolution. Eye degeneration in the blind mole rat (BMR; Nannospalax galili) and other subterranean mammals is significantly associated with widespread divergence of eye regulatory elements, but the effect of these regulatory mutations on eye development and function has not been explored. Here, we investigate the effect of mutations observed in the BMR sequence of a conserved noncoding element upstream of Tdrd7, a pleiotropic gene required for lens development and spermatogenesis. We first show that this conserved element is a transcriptional repressor in lens cells and that the BMR sequence partially lost repressor activity. Next, we recapitulated evolutionary changes in this element by precisely replacing the endogenous regulatory element in a mouse line by the orthologous BMR sequence with CRISPR–Cas9. Strikingly, this repressor replacement caused a more than 2-fold upregulation of Tdrd7 in the developing lens; however, increased mRNA level does not result in a corresponding increase in TDRD7 protein nor an obvious lens phenotype, possibly explained by buffering at the posttranscriptional level. Our results are consistent with eye degeneration in subterranean mammals having a polygenic basis where many small-effect mutations in different eye-regulatory elements collectively contribute to phenotypic differences.

scholarly journals Genome-wide identification and characterization of lectin receptor-like kinase gene family in cucumber and expression profiling analysis under different treatments

2020 ◽  
Author(s):  
Duo Lv ◽  
Gang Wang ◽  
Liang-Rong Xiong ◽  
Jing-Xian Sun ◽  
Yue Chen ◽  
...  
Keyword(s):  
Gene Family ◽  
Stress Responses ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Pcr Analysis ◽  
Kinase Gene ◽  
Lectin Receptor ◽  
Genome Wide ◽  
Cucumber Genome ◽  
And Function

Abstract Background: Lectin receptor-like kinases (LecRLKs) are a class of membrane proteins found in plants that are involved in diverse functions, including plant development and stress responses. Although LecRLK families have been identified in a variety of plants, a comprehensive analysis has not yet been undertaken in cucumber (Cucumis sativus L.). Results: In this study, 46 putative LecRLK genes were identified in cucumber genome, including 23 G-type, 22 L-type and 1 C-type LecRLK genes. They unequally distributed on all 7 chromosomes with a clustering trendency. Most of the genes in the cucumber LecRLK (CsLecRLK) gene family lacked introns. In addition, there were many regulatory elements associated with phytohormone and stress on these genes’ promoters. Transcriptome data demonstrated that distinct expression patterns of CsLecRLK genes in various tissues. Furthermore, we found that each member of the CsLecRLK family had its own unique expression pattern under hormone and stress treatment by the quantitative real time PCR (qRT-PCR) analysis.Conclusion: This study provides a better understanding of the evolution and function of LecRLK gene family in cucumber, and opens the possibility to explore the roles that LecRLKs might play in the life cycle of cucumber.

scholarly journals Genome-Wide Identification and Characterization of Lectin Receptor-Like Kinase Gene Family in Cucumber and Expression Profiling Analysis under Different Treatments

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1032 ◽  
Author(s):  
Duo Lv ◽  
Gang Wang ◽  
Liang-Rong Xiong ◽  
Jing-Xian Sun ◽  
Yue Chen ◽  
...  
Keyword(s):  
Gene Family ◽  
Stress Responses ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Pcr Analysis ◽  
Kinase Gene ◽  
Cucumis Sativus L ◽  
Lectin Receptor ◽  
Genome Wide ◽  
And Function

Lectin receptor-like kinases (LecRLKs) are a class of membrane proteins found in plants that are involved in diverse functions, including plant development and stress responses. Although LecRLK families have been identified in a variety of plants, a comprehensive analysis has not yet been undertaken in cucumber (Cucumis sativus L.). In this study, 46 putative LecRLK genes were identified in the cucumber genome, including 23 G-type and 22 L-type, and one C-type LecRLK gene. They were unequally distributed on all seven chromosomes, with a clustering tendency. Most of the genes in the cucumber LecRLK (CsLecRLK) gene family lacked introns. In addition, there were many regulatory elements associated with phytohormones and stress on these genes’ promoters. Transcriptome data demonstrated distinct expression patterns of CsLecRLK genes in various tissues. Furthermore, we found that each member of the CsLecRLK family had its own unique expression pattern under hormone and stress treatment by the quantitative real-time PCR (qRT-PCR) analysis. This study provides a better understanding of the character and function of the LecRLK gene family in cucumber and opens up the possibility to exploring the roles that LecRLKs might play in the life cycle of cucumber.

scholarly journals Genomic organization, expression, and phylogenetic analysis of Ca2+ channel β4 genes in 13 vertebrate species

2008 ◽  
Vol 35 (2) ◽  
pp. 133-144 ◽  
Author(s):  
Alicia M. Ebert ◽  
Catherine A. McAnelly ◽  
Anne V. Handschy ◽  
Rachel Lockridge Mueller ◽  
William A. Horne ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Alternative Splicing ◽  
Membrane Trafficking ◽  
Sequence Divergence ◽  
Tissue Expression ◽  
Regulatory Elements ◽  
Evolutionary Divergence ◽  
Voltage Dependent ◽  
Intron Structure ◽  
And Function

The Ca2+ channel β-subunits, encoded by CACNB genes 1–4, are membrane-associated guanylate kinase (MAGUK) proteins. As auxiliary subunits of voltage-gated Ca2+ channels, the β-subunits facilitate membrane trafficking of the pore-forming α1 subunits and regulate voltage-dependent channel gating. In this report, we investigate whether two zebrafish β4 genes, β4.1 and β4.2, have diverged in structure and function over time. Comparative expression analyses indicated that β4.1 and β4.2 were expressed in separable domains within the developing brain and other tissues. Alternative splicing in both genes was subject to differential temporal and spatial regulation, with some organs expressing different subsets of β4.1 and β4.2 transcript variants. We used several genomic tools to identify and compare predicted cDNAs for eight teleost and five tetrapod β4 genes. Teleost species had either one or two β4 paralogs, whereas each tetrapod species contained only one. Teleost β4.1 and β4.2 genes had regions of sequence divergence, but compared with tetrapod β4s, they exhibited similar exon/intron structure, strong conservation of residues involved in α1 subunit binding, and similar 5′ alternative splicing. Phylogenetic results are consistent with the duplicate teleost β4 genes resulting from the teleost whole genome duplication. Following duplication, the β4.1 genes have evolved faster than β4.2 genes. We identified disproportionately large second and third introns in several β4 genes, which we propose may provide regulatory elements contributing to their differential tissue expression. In sum, both mRNA expression data and phylogenetic analysis support the evolutionary divergence of β4.1 and β4.2 subunit function.

scholarly journals Recapitulating evolutionary divergence in a single cis-regulatory element is sufficient to cause expression changes of the lens gene Tdrd7

2020 ◽  
Author(s):  
Juliana G. Roscito ◽  
Kaushikaram Subramanian ◽  
Ronald Naumann ◽  
Mihail Sarov ◽  
Anna Shevchenko ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Mrna Level ◽  
Regulatory Elements ◽  
Evolutionary Divergence ◽  
Phenotypic Differences ◽  
Evolutionary Changes ◽  
Mole Rat ◽  
Regulatory Mutations ◽  
Subterranean Mammals ◽  
And Function

ABSTRACTMutations in cis-regulatory elements play important roles for phenotypic changes during evolution. Eye degeneration in the blind mole rat (BMR) and other subterranean mammals is significantly associated with widespread divergence of eye regulatory elements, but the effect of these regulatory mutations on eye development and function has not been explored. Here, we investigate the effect of mutations observed in the BMR sequence of a conserved non-coding element upstream of Tdrd7, a pleiotropic gene required for lens development and spermatogenesis. We first show that this conserved element is a transcriptional repressor in lens cells and that the BMR sequence partially lost repressor activity. Next, we recapitulated the evolutionary changes by precisely replacing the endogenous regulatory element in a mouse line by the orthologous BMR sequence with CRISPR-Cas9. Strikingly, this repressor element has a large effect, causing a more than two-fold up-regulation of Tdrd7 in developing lens. Interestingly, the increased mRNA level does not result in a corresponding increase in TDRD7 protein nor an obvious lens phenotype, likely explained by buffering at the posttranscriptional level. Our results are consistent with eye degeneration in subterranean mammals having a polygenic basis where many small-effect mutations in different eye-regulatory elements collectively contribute to phenotypic differences.

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