Gene Regulatory Networks
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Dynamical Gene Regulatory Networks Are Tuned by Transcriptional Autoregulation with Microrna Feedback Thomas G
www.nature.com/scientificreports OPEN Dynamical gene regulatory networks are tuned by transcriptional autoregulation with microRNA feedback Thomas G. Minchington1, Sam Grifths‑Jones2* & Nancy Papalopulu1* Concepts from dynamical systems theory, including multi‑stability, oscillations, robustness and stochasticity, are critical for understanding gene regulation during cell fate decisions, infammation and stem cell heterogeneity. However, the prevalence of the structures within gene networks that drive these dynamical behaviours, such as autoregulation or feedback by microRNAs, is unknown. We integrate transcription factor binding site (TFBS) and microRNA target data to generate a gene interaction network across 28 human tissues. This network was analysed for motifs capable of driving dynamical gene expression, including oscillations. Identifed autoregulatory motifs involve 56% of transcription factors (TFs) studied. TFs that autoregulate have more interactions with microRNAs than non‑autoregulatory genes and 89% of autoregulatory TFs were found in dual feedback motifs with a microRNA. Both autoregulatory and dual feedback motifs were enriched in the network. TFs that autoregulate were highly conserved between tissues. Dual feedback motifs with microRNAs were also conserved between tissues, but less so, and TFs regulate diferent combinations of microRNAs in a tissue‑dependent manner. The study of these motifs highlights ever more genes that have complex regulatory dynamics. These data provide a resource for the identifcation of TFs which regulate the dynamical properties of human gene expression. Cell fate changes are a key feature of development, regeneration and cancer, and are ofen thought of as a “land- scape” that cells move through1,2. Cell fate changes are driven by changes in gene expression: turning genes on or of, or changing their levels above or below a threshold where a cell fate change occurs. -
Systematic Comparison of Sea Urchin and Sea Star Developmental Gene Regulatory Networks Explains How Novelty Is Incorporated in Early Development
ARTICLE https://doi.org/10.1038/s41467-020-20023-4 OPEN Systematic comparison of sea urchin and sea star developmental gene regulatory networks explains how novelty is incorporated in early development Gregory A. Cary 1,3,5, Brenna S. McCauley1,4,5, Olga Zueva1, Joseph Pattinato1, William Longabaugh2 & ✉ Veronica F. Hinman 1 1234567890():,; The extensive array of morphological diversity among animal taxa represents the product of millions of years of evolution. Morphology is the output of development, therefore phenotypic evolution arises from changes to the topology of the gene regulatory networks (GRNs) that control the highly coordinated process of embryogenesis. A particular challenge in under- standing the origins of animal diversity lies in determining how GRNs incorporate novelty while preserving the overall stability of the network, and hence, embryonic viability. Here we assemble a comprehensive GRN for endomesoderm specification in the sea star from zygote through gastrulation that corresponds to the GRN for sea urchin development of equivalent territories and stages. Comparison of the GRNs identifies how novelty is incorporated in early development. We show how the GRN is resilient to the introduction of a transcription factor, pmar1, the inclusion of which leads to a switch between two stable modes of Delta-Notch signaling. Signaling pathways can function in multiple modes and we propose that GRN changes that lead to switches between modes may be a common evolutionary mechanism for changes in embryogenesis. Our data additionally proposes a model in which evolutionarily conserved network motifs, or kernels, may function throughout development to stabilize these signaling transitions. 1 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA. -
An Automatic Design Framework of Swarm Pattern Formation Based on Multi-Objective Genetic Programming
JOURNAL OF LATEX CLASS FILES, VOL. 14, NO. 8, AUGUST 2015 1 An Automatic Design Framework of Swarm Pattern Formation based on Multi-objective Genetic Programming Zhun Fan, Senior Member, IEEE, Zhaojun Wang, Xiaomin Zhu, Bingliang Hu, Anmin Zou, and Dongwei Bao Abstract—Most existing swarm pattern formation methods predetermined trajectory and maintain a specific swarm pattern depend on a predefined gene regulatory network (GRN) structure in the execution of tasks. For example, Jin [11] proposed a that requires designers’ priori knowledge, which is difficult to hierarchical gene regulatory network for adaptive multi-robot adapt to complex and changeable environments. To dynamically adapt to the complex and changeable environments, we propose pattern formation. In this work, the swarm pattern is designed an automatic design framework of swarm pattern formation as a band of circle, which encircles targets in a dynamic based on multi-objective genetic programming. The proposed environments. In the latter case of using adaptive formation, framework does not need to define the structure of the GRN- swarm robots follow an adaptive pattern to encircle targets in based model in advance, and it applies some basic network motifs the environment. For example, Oh et al. [12] have introduced to automatically structure the GRN-based model. In addition, a multi-objective genetic programming (MOGP) combines with an evolving hierarchical gene regulatory network for morpho- NSGA-II, namely MOGP-NSGA-II, to balance the complexity genetic pattern formation in order to generate adaptive patterns and accuracy of the GRN-based model. In evolutionary process, which are adaptable to dynamic environments. an MOGP-NSGA-II and differential evolution (DE) are applied to In addition, swarm pattern formation has been widely ex- optimize the structures and parameters of the GRN-based model plored in recent years, which can be divided into four cate- in parallel. -
Temporal Flexibility of Gene Regulatory Network Underlies a Novel Wing Pattern in Flies
Temporal flexibility of gene regulatory network underlies a novel wing pattern in flies Héloïse D. Dufoura,b, Shigeyuki Koshikawa (越川滋行)a,b,1,2,3, and Cédric Fineta,b,3,4 aHoward Hughes Medical Institute, University of Wisconsin, Madison, WI 53706; and bLaboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706 Edited by Denis Duboule, University of Geneva, Geneva 4, Switzerland, and approved April 6, 2020 (received for review February 3, 2020) Organisms have evolved endless morphological, physiological, and Nevertheless, it does not explain how the new expression of behavioral novel traits during the course of evolution. Novel traits the coopted toolkit genes does not interfere with the develop- were proposed to evolve mainly by orchestration of preexisting ment of the tissue. Some authors have suggested that the reuse genes. Over the past two decades, biologists have shown that of toolkit genes might only happen during late development after cooption of gene regulatory networks (GRNs) indeed underlies completion of the early function of the redeployed genes (21, 22, numerous evolutionary novelties. However, very little is known 29). However, little is known about the properties of a GRN that about the actual GRN properties that allow such redeployment. allow the cooption of one or several of its components/genes Here we have investigated the generation and evolution of the without impairing the development of the tissue. complex wing pattern of the fly Samoaia leonensis. We show that In this study, we use the complex wing pigmentation pattern of the transcription factor Engrailed is recruited independently from the fly species Samoaia leonensis as a model to address how the the other players of the anterior–posterior specification network to generate a new wing pattern. -
A Computational Model Inspired by Gene Regulatory Networks
Rui Miguel Lourenço Lopes A Computational Model Inspired by Gene Regulatory Networks Doctoral thesis submitted to the Doctoral Program in Information Science and Technology, supervised by Full Professor Doutor Ernesto Jorge Fernandes Costa, and presented to the Department of Informatics Engineering of the Faculty of Sciences and Technology of the University of Coimbra. January 2015 A Computational Model Inspired by Gene Regulatory Networks A thesis submitted to the University of Coimbra in partial fulfillment of the requirements for the Doctoral Program in Information Science and Technology by Rui Miguel Lourenço Lopes [email protected] Department of Informatics Engineering Faculty of Sciences and Technology University of Coimbra Coimbra, January 2015 Financial support by Fundação para a Ciência e a Tecnologia, through the PhD grant SFRH/BD/69106/2010. A Computational Model Inspired by Gene Regulatory Networks ©2015 Rui L. Lopes ISBN 978-989-20-5460-5 Cover image: Composition of a Santa Fe trail program evolved by ReNCoDe overlaid on the ancestors, with a 3D model of the DNA crystal structure (by Paul Hakimata). This dissertation was prepared under the supervision of Ernesto J. F. Costa Full Professor of the Department of Informatics Engineering of the Faculty of Sciences and Tecnology of the University of Coimbra In loving memory of my father. Acknowledgements Thank you very much to Prof. Ernesto Costa, for his vision on research and education, for all the support and contributions to my ideas, and for the many life stories that always lighten the mood. Thank you also to Nuno Lourenço for the many discussions, shared books, and his constant helpfulness. -
Spectrum of Mutations and Genotype ± Phenotype Analysis in Currarino Syndrome
European Journal of Human Genetics (2001) 9, 599 ± 605 ã 2001 Nature Publishing Group All rights reserved 1018-4813/01 $15.00 www.nature.com/ejhg ARTICLE Spectrum of mutations and genotype ± phenotype analysis in Currarino syndrome Joachim KoÈchling1, Mohsen Karbasiyan2 and Andre Reis*,2,3 1Department of Pediatric Oncology/Hematology, ChariteÂ, Humboldt University, Berlin, Germany; 2Institute of Human Genetics, ChariteÂ, Humboldt University, Berlin, Germany; 3Institute of Human Genetics, Friedrich- Alexander University Erlangen-NuÈrnberg, Erlangen, Germany The triad of a presacral tumour, sacral agenesis and anorectal malformation constitutes the Currarino syndrome which is caused by dorsal-ventral patterning defects during embryonic development. The syndrome occurs in the majority of patients as an autosomal dominant trait associated with mutations in the homeobox gene HLXB9 which encodes the nuclear protein HB9. However, genotype ± phenotype analyses have been performed only in a few families and there are no reports about the specific impact of HLXB9 mutations on HB9 function. We performed a mutational analysis in 72 individuals from nine families with Currarino syndrome. We identified a total of five HLXB9 mutations, four novel and one known mutation, in four out of four families and one out of five sporadic cases. Highly variable phenotypes and a low penetrance with half of all carriers being clinically asymptomatic were found in three families, whereas affected members of one family showed almost identical phenotypes. However, an obvious genotype ± phenotype correlation was not found. While HLXB9 mutations were diagnosed in 23 patients, no mutation or microdeletion was detected in four sporadic patients with Currarino syndrome. The distribution pattern of here and previously reported HLXB9 mutations indicates mutational predilection sites within exon 1 and the homeobox. -
Solutions for Practice Problems for Molecular Biology, Session 5
Solutions to Practice Problems for Molecular Biology, Session 5: Gene Regulation and the Lac Operon Question 1 a) How does lactose (allolactose) promote transcription of LacZ? 1) Lactose binds to the polymerase and increases efficiency. 2) Lactose binds to a repressor protein, and alters its conformation to prevent it from binding to the DNA and interfering with the binding of RNA polymerase. 3) Lactose binds to an activator protein, which can then help the RNA polymerase bind to the promoter and begin transcription. 4) Lactose prevents premature termination of transcription by directly binding to and bending the DNA. Solution: 2) Lactose binds to a repressor protein, and alters its conformation to prevent it from binding to the DNA and interfering with the binding of RNA polymerase. b) What molecule is used to signal low glucose levels to the Lac operon regulatory system? 1) Cyclic AMP 2) Calcium 3) Lactose 4) Pyruvate Solution: 1) Cyclic AMP. Question 2 You design a summer class where you recreate experiments studying the lac operon in E. coli (see schematic below). In your experiments, the activity of the enzyme b-galactosidase (β -gal) is measured by including X-gal and IPTG in the growth media. X-gal is a lactose analog that turns blue when metabolisize by b-gal, but it does not induce the lac operon. IPTG is an inducer of the lac operon but is not metabolized by b-gal. I O lacZ Plac Binding site for CAP Pi Gene encoding β-gal Promoter for activator protein Repressor (I) a) Which of the following would you expect to bind to β-galactosidase? Circle all that apply. -
Evolutionary Developmental Biology 573
EVOC20 29/08/2003 11:15 AM Page 572 Evolutionary 20 Developmental Biology volutionary developmental biology, now often known Eas “evo-devo,” is the study of the relation between evolution and development. The relation between evolution and development has been the subject of research for many years, and the chapter begins by looking at some classic ideas. However, the subject has been transformed in recent years as the genes that control development have begun to be identified. This chapter looks at how changes in these developmental genes, such as changes in their spatial or temporal expression in the embryo, are associated with changes in adult morphology. The origin of a set of genes controlling development may have opened up new and more flexible ways in which evolution could occur: life may have become more “evolvable.” EVOC20 29/08/2003 11:15 AM Page 573 CHAPTER 20 / Evolutionary Developmental Biology 573 20.1 Changes in development, and the genes controlling development, underlie morphological evolution Morphological structures, such as heads, legs, and tails, are produced in each individual organism by development. The organism begins life as a single cell. The organism grows by cell division, and the various cell types (bone cells, skin cells, and so on) are produced by differentiation within dividing cell lines. When one species evolves into Morphological evolution is driven another, with a changed morphological form, the developmental process must have by developmental evolution changed too. If the descendant species has longer legs, it is because the developmental process that produces legs has been accelerated, or extended over time. -
Gene Regulatory Network Reconstruction Using Bayesian
1 Gene regulatory network reconstruction using Bayesian networks, the Dantzig selector, the Lasso and their meta-analysis Matthieu Vignes1∗, Jimmy Vandel1, David Allouche1, Nidal Ramadan-Alban1, Christine Cierco-Ayrolles1, Thomas Schiex1, Brigitte Mangin1, Simon de Givry1 1 SaAB Team/BIA Unit, INRA Toulouse, Castanet-Tolosan, France ∗ E-mail: [email protected] Abstract Modern technologies and especially next generation sequencing facilities are giving a cheaper access to genotype and genomic data measured on the same sample at once. This creates an ideal situation for multifactorial experiments designed to infer gene regulatory networks. The fifth \Dialogue for Reverse Engineering Assessments and Methods" (DREAM5) challenges are aimed at assessing methods and as- sociated algorithms devoted to the inference of biological networks. Challenge 3 on \Systems Genetics" proposed to infer causal gene regulatory networks from different genetical genomics data sets. We in- vestigated a wide panel of methods ranging from Bayesian networks to penalised linear regressions to analyse such data, and proposed a simple yet very powerful meta-analysis, which combines these inference methods. We present results of the Challenge as well as more in-depth analysis of predicted networks in terms of structure and reliability. The developed meta-analysis was ranked first among the 16 teams participating in Challenge 3A. It paves the way for future extensions of our inference method and more accurate gene network estimates in the context of genetical genomics. Introduction Inferring gene regulatory networks. Gene regulatory networks (GRN) are simplified representa- tions of mechanisms that make up the functioning of an organism under given conditions. A node in such a network stands for a gene i.e. -
Myths and Legends of the Baldwin Effect
Myths and Legends of the Baldwin Effect Peter Turney Institute for Information Technology National Research Council Canada Ottawa, Ontario, Canada, K1A 0R6 [email protected] Abstract ary computation when there is an evolving population of learning individuals (Ackley and Littman, 1991; Belew, This position paper argues that the Baldwin effect 1989; Belew et al., 1991; French and Messinger, 1994; is widely misunderstood by the evolutionary Hart, 1994; Hart and Belew, 1996; Hightower et al., 1996; computation community. The misunderstandings Whitley and Gruau, 1993; Whitley et al., 1994). This syn- appear to fall into two general categories. Firstly, ergetic effect is usually called the Baldwin effect. This has it is commonly believed that the Baldwin effect is produced the misleading impression that there is nothing concerned with the synergy that results when more to the Baldwin effect than synergy. A myth or legend there is an evolving population of learning indi- has arisen that the Baldwin effect is simply a special viduals. This is only half of the story. The full instance of synergy. One of the goals of this paper is to story is more complicated and more interesting. dispel this myth. The Baldwin effect is concerned with the costs Roughly speaking (we will be more precise later), the and benefits of lifetime learning by individuals in Baldwin effect has two aspects. First, lifetime learning in an evolving population. Several researchers have individuals can, in some situations, accelerate evolution. focussed exclusively on the benefits, but there is Second, learning is expensive. Therefore, in relatively sta- much to be gained from attention to the costs. -
Principles of Differentiation and Morphogenesis
Swarthmore College Works Biology Faculty Works Biology 2016 Principles Of Differentiation And Morphogenesis Scott F. Gilbert Swarthmore College, [email protected] R. Rice Follow this and additional works at: https://works.swarthmore.edu/fac-biology Part of the Biology Commons Let us know how access to these works benefits ouy Recommended Citation Scott F. Gilbert and R. Rice. (2016). 3rd. "Principles Of Differentiation And Morphogenesis". Epstein's Inborn Errors Of Development: The Molecular Basis Of Clinical Disorders On Morphogenesis. 9-21. https://works.swarthmore.edu/fac-biology/436 This work is brought to you for free by Swarthmore College Libraries' Works. It has been accepted for inclusion in Biology Faculty Works by an authorized administrator of Works. For more information, please contact [email protected]. 2 Principles of Differentiation and Morphogenesis SCOTT F. GILBERT AND RITVA RICE evelopmental biology is the science connecting genetics with transcription factors, such as TFHA and TFIIH, help stabilize the poly anatomy, making sense out of both. The body builds itself from merase once it is there (Kostrewa et al. 2009). Dthe instructions of the inherited DNA and the cytoplasmic system that Where and when a gene is expressed depends on another regula interprets the DNA into genes and creates intracellular and cellular tory unit of the gene, the enhancer. An enhancer is a DNA sequence networks to generate the observable phenotype. Even ecological fac that can activate or repress the utilization of a promoter, controlling tors such as diet and stress may modify the DNA such that different the efficiency and rate of transcription from that particular promoter. -
Lamarck's Ladder
Lamarck’s Ladder Overview Darwinism is a theory of biological evolution developed by the English naturalist Charles Darwin (1809–1882) and others. It states that all species of organisms arise and develop through the natural selection of small, inherited variations that increase the individual's ability to compete, survive, and reproduce. The environment plays a critical role in the natural selection process of Darwinian evolution through the phenotypic variation produced over time by small genetic changes to the DNA sequence, such as beneficial random mutations. However, the vast majority of environmental factors cannot directly alter DNA sequence. Jean-Baptiste Pierre Antoine de Monet, chevalier de Lamarck (1744 – 1829), often known simply as Lamarck, was a French naturalist. Before Darwin, Lamarck was one of the first scientists to support the Theory of Evolution. His theory was that species evolved based on the behavior of their parents. His hypothesis stated that an organism can pass on phenotypes acquired because of environmental pressures within their lifetime and pass them to its offspring. One of his most famous examples is his explanation of a giraffe’s long neck. He proposed that the continuous stretching of the neck by the giraffe to reach higher and higher leaves caused the muscles in the neck to strengthen and gradually lengthen over a period of time, which gave rise to longer necks in giraffes. Lamarck’s hypothesis was rejected and later became associated with flawed science concepts. However, scientists today debate whether advances in the field of transgenerational epigenetics indicate that Lamarck was correct, at least to some extent.