THE GENETICAL SOCIETY—ABSTRACTS of PAPERS of A1059metdphageswas Isolated on Minimal 5
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Reinhart Heinrich (1946–2006) Pioneer in Systems Biology
NEWS & VIEWS NATURE|Vol 444|7 December 2006 OBITUARY Reinhart Heinrich (1946–2006) Pioneer in systems biology. In biology, mathematical systems analysis where he showed that the flux of was until recently nearly invisible in the reaction was shared by several the dazzling light of twentieth-century enzymes. Much later, he extended discoveries. But it has emerged from the his ideas to signal-transduction shadows in the field of systems biology, pathways, introducing control a subject buoyed by immense data sets, coefficients to dynamic processes. conveyed by heavy computing power, and Sticking to real examples, such as addressing seemingly incomprehensible the Wnt signalling and MAP kinase forms of complexity. If systems biology has pathways, he again demonstrated heroes, one of them is Reinhart Heinrich, a that new properties and constraints former professor at the Humboldt University emerge when the individual steps in Berlin, who died on 23 October, aged are combined into a complete 60. His most famous accomplishment was pathway. metabolic control theory, published in Heinrich also pointed the way to 1974 with Tom Rapoport and formulated considerations of optimality theory independently by Henrik Kacser and James and evolution that will confront A. Burns in Edinburgh, UK. systems biology for the next From the 1930s to the 1960s, biochemists century. The question of evolution were busy describing metabolic pathways, lies just beneath any effort to just as molecular biologists today are understand biology. Yet in most feverishly trying to inventory the cell’s cases, physiological function and gene-transcription and signalling circuits. evolutionary change are considered The basic kinetic features of the enzymes in distinct and are investigated by the major pathways were studied in great different people. -
Review Heterochronic Genes and the Nature of Developmental Time
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Current Biology 17, R425–R434, June 5, 2007 ª2007 Elsevier Ltd All rights reserved DOI 10.1016/j.cub.2007.03.043 Heterochronic Genes and the Nature of Review Developmental Time Eric G. Moss that have arisen to solve the problem of regulated tim- ing in animal development. Timing is a fundamental issue in development, with Heterochrony and Developmental Timing a range of implications from birth defects to evolu- in Evolution tion. In the roundworm Caenorhabditis elegans, Changes in developmental timing have long been be- the heterochronic genes encode components of lieved to be a major force in the evolution of morphol- a molecular developmental timing mechanism. This ogy [1]. A variety of changes is encompassed by the mechanism functions in diverse cell types through- concept of ‘heterochrony’ — differences in the relative out the animal to specify cell fates at each larval timing of developmental events between two closely stage. MicroRNAs play an important role in this related species. A classic example of heterochrony is mechanism by stage-specifically repressing cell- the axolotl. This salamander reaches sexual maturity fate regulators. Recent studies reveal the surprising without undergoing metamorphosis, such that its complexity surrounding this regulation — for exam- non-gonadal tissues retain larval features of other ple, a positive feedback loop may make the regula- salamanders. Different species of axolotls exhibit ge- tion more robust, and certain components of the netic differences in the production or activity of thyroid mechanism are expressed in brief periods at each hormones that trigger metamorphosis from aquatic stage. -
Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B
Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B. M ü ller, G ü nter P. Wagner, and Werner Callebaut, editors The Evolution of Cognition , edited by Cecilia Heyes and Ludwig Huber, 2000 Origination of Organismal Form: Beyond the Gene in Development and Evolutionary Biology , edited by Gerd B. M ü ller and Stuart A. Newman, 2003 Environment, Development, and Evolution: Toward a Synthesis , edited by Brian K. Hall, Roy D. Pearson, and Gerd B. M ü ller, 2004 Evolution of Communication Systems: A Comparative Approach , edited by D. Kimbrough Oller and Ulrike Griebel, 2004 Modularity: Understanding the Development and Evolution of Natural Complex Systems , edited by Werner Callebaut and Diego Rasskin-Gutman, 2005 Compositional Evolution: The Impact of Sex, Symbiosis, and Modularity on the Gradualist Framework of Evolution , by Richard A. Watson, 2006 Biological Emergences: Evolution by Natural Experiment , by Robert G. B. Reid, 2007 Modeling Biology: Structure, Behaviors, Evolution , edited by Manfred D. Laubichler and Gerd B. M ü ller, 2007 Evolution of Communicative Flexibility: Complexity, Creativity, and Adaptability in Human and Animal Communication , edited by Kimbrough D. Oller and Ulrike Griebel, 2008 Functions in Biological and Artifi cial Worlds: Comparative Philosophical Perspectives , edited by Ulrich Krohs and Peter Kroes, 2009 Cognitive Biology: Evolutionary and Developmental Perspectives on Mind, Brain, and Behavior , edited by Luca Tommasi, Mary A. Peterson, and Lynn Nadel, 2009 Innovation in Cultural Systems: Contributions from Evolutionary Anthropology , edited by Michael J. O ’ Brien and Stephen J. Shennan, 2010 The Major Transitions in Evolution Revisited , edited by Brett Calcott and Kim Sterelny, 2011 Transformations of Lamarckism: From Subtle Fluids to Molecular Biology , edited by Snait B. -
Fitness As a Function of Β-Galactosidase Activity In
Genet. Res., Camb. (1986), 48, pp. 1-8 With 3 text-figures Printed in Great Britain Fitness as a function of /?-galactosidase activity in Escherichia coli ANTONY M. DEAN, DANIEL E. DYKHUIZEN AND DANIEL L. HARTL Department of Genetics, Washington University School of Medicine, St Louis, Missouri USA 63110-1095 (Received 12 July 1985 and in revised form 13 January 1986) Summary Chemostat cultures in which the limiting nutrient was lactose have been used to study the relative growth rate of Escherichia coli in relation to the enzyme activity of /?-galactosidase. A novel genetic procedure was employed in order to obtain amino acid substitutions within the /acZ-encoded /?-galactosidase that result in differences in enzyme activity too small to be detected by ordinary mutant screens. The cryptic substitutions were obtained as spontaneous revertants of nonsense mutations within the lacZ gene, and the enzymes differing from wild type were identified by means of polyacrylamide gel electrophoresis or thermal denaturation studies. The relation between enzyme activity and growth rate of these and other mutants supports a model of intermediary metabolism in which the flux of substrate through a metabolic pathway is represented by a concave function of the activity of any enzyme in the pathway. The consequence is that small differences in enzyme activity from wild type result in even smaller changes in fitness. 1. Introduction sidase activity and growth rate in E. coli, together with a novel genetic technique for obtaining amino acid In the seminal paper, Kacser & Burns (1973) demon- strated that the net flux through a simple linear meta- substitutions that result in electrophoretic or thermo- bolic pathway should be a concave function of the lability differences from wild type. -
Uva-DARE (Digital Academic Repository)
UvA-DARE (Digital Academic Repository) Henrik Kacser 1918-1995: Metabolism of control. Westerhoff, H.V. DOI 10.1016/S0167-7799(00)88956-8 Publication date 1995 Published in Trends in Biotechnology Link to publication Citation for published version (APA): Westerhoff, H. V. (1995). Henrik Kacser 1918-1995: Metabolism of control. Trends in Biotechnology, 13, 245. https://doi.org/10.1016/S0167-7799(00)88956-8 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:25 Sep 2021 245 f orum Henrik Kacser (19184995): metabolism of control Obituary Henrik Kacser has been referred missed the rate-limiting step. He funding agency had allowed much to as the ‘pope’ of Metabolic much appreciated -
Sonic Hedgehog Signaling in Limb Development
REVIEW published: 28 February 2017 doi: 10.3389/fcell.2017.00014 Sonic Hedgehog Signaling in Limb Development Cheryll Tickle 1* and Matthew Towers 2* 1 Department of Biology and Biochemistry, University of Bath, Bath, UK, 2 Department of Biomedical Science, The Bateson Centre, University of Sheffield, Western Bank, Sheffield, UK The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e.g., shoulder to digits axis) of the limb. It has been shown that Shh signaling can specify antero-posterior positional values in Edited by: limb buds in both a concentration- (paracrine) and time-dependent (autocrine) fashion. Andrea Erika Münsterberg, University of East Anglia, UK Currently there are several models for how Shh specifies positional values over time in the Reviewed by: limb buds of chick and mouse embryos and how this is integrated with growth. Extensive Megan Davey, work has elucidated downstream transcriptional targets of Shh signaling. Nevertheless, it University of Edinburgh, UK Robert Hill, remains unclear how antero-posterior positional values are encoded and then interpreted University of Edinburgh, UK to give the particular structure appropriate to that position, for example, the type of digit. -
Principles of Systems Biology and Dmitri Belyaev's Co-Selection of Traits
Principles of systems biology and Dmitri Belyaev’s co-selection of traits Hans V. Westerhoff and friends MCISB, MIB, SCEAS, University of Manchester SysBA, Universities of Amsterdam Systems Biology • What is it? • Principles – Lack of dominance (Kacser) – Co-selection (Belyaev) • Progress – Make Me My Model – The genome wide metabolic maps – Epigenetics and noise/cell diversity Bioinformatics: From biological data to information Systems Biology: From that information to understanding Systems Biology: From data to understanding: why is this such an issue? • Because the mapping from genome to function is extremely nonlinear • E.g.: – - – - The DNA in all our cells is the same, but: a heart cell is essentially different from a brain cell – - Self organization, bistability: Belousov, Zhabotinsky, Waddington, Ilya Prigogine, Boris Kholodenko Why systems biology? Cause 1 ~all functions are X network functions Multiple causality Cause 2 Cause 3 X Multifactorial X disease Impaired function 2006 Hornberg et al: ‘Cancer: a systems biology disease’. Now: ‘virtually all disease are Systems Biology diseases.’ This causes the ‘missing heritability problem (Baranov; Stepanov)’ Systems Biology= • The Science that • aims to understand • principles governing • how the biological functions • arise from the interactions = from the networking This leads to precision, personalized, 4P medicine, PPP4M And to precision biotechnology Systems Biology • What is it? • Principles – Lack of dominance (Kacser) – Co-selection (Belyaev) • Progress – Make Me My Model – The genome wide metabolic maps – Epigenetics and noise/cell diversity Henrik Kacser (Student of Waddell) Henrik Kacser Recessivity of most lack-of-function mutations Lack of dominance: No loss of function in heterozygote Lack of dominance: observation F0 F0’ F1 (knock out) X Function= 100% 0% 95% Flux J Lack of dominance: single molecule explanation fails F0 F0’ F1 AA 00 A0 X This is almost always incorre Function= 100% 100% 50% Flux J ct Cf. -
2019.12.20.883900V1.Full.Pdf
bioRxiv preprint doi: https://doi.org/10.1101/2019.12.20.883900; this version posted December 20, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Title 2 Sequence heterochrony led to a gain of functionality in an immature 3 stage of the central complex: a fly-beetle insight 4 Short title: Sequence heterochrony in central complex evolution 5 6 Authors: 7 Max S. Farnwortha,c, Kolja N. Eckermannb,c, Gregor Buchera,* 8 9 a Department of Evolutionary Developmental Genetics, Johann-Friedrich-Blumenbach Institute, GZMB, 10 University of Göttingen, Göttingen, Germany, b Department of Developmental Biology, Johann-Friedrich- 11 Blumenbach Institute, GZMB, University of Göttingen, Göttingen, Germany, c Göttingen Graduate Center for 12 Molecular Biosciences, Neurosciences and Biophysics (GGNB), Göttingen, Germany 13 14 * Corresponding author: Gregor Bucher 15 Email: [email protected] 16 17 ORCID: Max S. Farnworth https://orcid.org/0000-0003-2418-3203, Gregor Bucher 18 https://orcid.org/0000-0002-4615-6401 19 - 1 - bioRxiv preprint doi: https://doi.org/10.1101/2019.12.20.883900; this version posted December 20, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 20 Abstract 21 Animal behavior is guided by the brain. -
The Molecular Basis of Dominance
THE MOLECULAR BASIS OF DOMINANCE HENRIK KACSER AND JAMES A. BURNS Deprrrtment of Genetics, Uniuersity of Edinburgh, Edinburgh Manuscript received September 3, 1980 ABSTRACT The best known genes of microbes, mice and men are those that specify enzymes. Wild type, mutant and heterozygote for variants of such genes differ in the catalytic activity at the step in the enzyme network specified by the gene in question. The effect on the respective phenotypes of such changes in catalytic activity, however, is not defined by the enzyme change as estimated by in vitro determination of the activities obtained from the extracts of the three types. In vivo enzymes do not act in isolation, but are kinetically linked to other enzymes uiu their substrates and products. These interactions modify the effect of enzyme variation on the phenotype, depending on the nature and quantity of the other enzymes present. An output of such a system, say a flux, is therefore a systemic property, and its response to variation at one locus must be measured in the whole system. This response is best described by the sensi- tivity coefficient, Z, which is defined by the fractional change in flux over the fractional change in enzyme activity. Its magnitude determines the extent to which a particular enzyme “controls” a particular flux or phenotype and, implicitly, determines the values that the three phenotypes will have. There are as many sensitivity coefficients for a given flux as there are enzymes in the system. It can be shown that the sum of all such coefficients equals unity. n Since n, the number of enzymes, is large, this summation property results in the individual coefficients being small. -
Homeobox Genes D11–D13 and A13 Control Mouse Autopod Cortical
Research article Homeobox genes d11–d13 and a13 control mouse autopod cortical bone and joint formation Pablo Villavicencio-Lorini,1,2 Pia Kuss,1,2 Julia Friedrich,1,2 Julia Haupt,1,2 Muhammed Farooq,3 Seval Türkmen,2 Denis Duboule,4 Jochen Hecht,1,5 and Stefan Mundlos1,2,5 1Max Planck Institute for Molecular Genetics, Berlin, Germany. 2Institute for Medical Genetics, Charité, Universitätsmedizin Berlin, Berlin, Germany. 3Human Molecular Genetics Laboratory, National Institute for Biotechnology & Genetic Engineering (NIBGE), Faisalabad, Pakistan. 4National Research Centre Frontiers in Genetics, Department of Zoology and Animal Biology, University of Geneva, Geneva, Switzerland. 5Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité, Universitätsmedizin Berlin, Berlin, Germany. The molecular mechanisms that govern bone and joint formation are complex, involving an integrated network of signaling pathways and gene regulators. We investigated the role of Hox genes, which are known to specify individual segments of the skeleton, in the formation of autopod limb bones (i.e., the hands and feet) using the mouse mutant synpolydactyly homolog (spdh), which encodes a polyalanine expansion in Hoxd13. We found that no cortical bone was formed in the autopod in spdh/spdh mice; instead, these bones underwent trabecular ossification after birth. Spdh/spdh metacarpals acquired an ovoid shape and developed ectopic joints, indicating a loss of long bone characteristics and thus a transformation of metacarpals into carpal bones. The perichon- drium of spdh/spdh mice showed abnormal morphology and decreased expression of Runt-related transcription factor 2 (Runx2), which was identified as a direct Hoxd13 transcriptional target. Hoxd11–/–Hoxd12–/–Hoxd13–/– tri- ple-knockout mice and Hoxd13–/–Hoxa13+/– mice exhibited similar but less severe defects, suggesting that these Hox genes have similar and complementary functions and that the spdh allele acts as a dominant negative. -
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. -
Geoffrey Herbert Beale, MBE, FRS, FRSE 11 June 1913 - 16 October 2009
Geoffrey Herbert Beale, MBE, FRS, FRSE 11 June 1913 - 16 October 2009 Geoffrey Beale was recognized internationally as a leading protozoan geneticist with an all-absorbing love of genetics, stimulated in the early part of his career by either working with or meeting many of the key figures who laid the foundations of modern genetics in the 1930s and 1940s. His work on the genetics of the surface antigens of Paramecium provided a conceptual breakthrough in our understanding of the role of the environment, the cytoplasm and the expression of genes, and he continued his interest in the role of cytoplasmic elements in heredity through studies on both the endosymbionts and mitochondria of Paramecium. He pioneered the genetic analysis of parasitic protozoa with his work on Plasmodium, and this stimulated many other scientists to take a genetic approach with these experimentally challenging organisms. Geoffrey was born in Wandsworth, London, on 11 June 1913, the son of Herbert Walter Beale and Elsie Beale (née Beaton). His family included an elder brother (Hugh) and two younger sisters (Margaret and Joan). When he was about five years old the family moved to Wallington, Surrey, where he spent the rest of his childhood as well as staying there during his university undergraduate and postgraduate studies. He attended Sutton County School, Surrey from 1923 until he obtained his higher school certificates in mathematics, physics and chemistry in 1931. His main interest at that time was music and he briefly considered the possibility that he might make music his career and he became an accomplished pianist and organist.