The Impact of Quasispecies Dynamics on the Use of Therapeutics
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Prebiological Evolution and the Metabolic Origins of Life
Prebiological Evolution and the Andrew J. Pratt* Metabolic Origins of Life University of Canterbury Keywords Abiogenesis, origin of life, metabolism, hydrothermal, iron Abstract The chemoton model of cells posits three subsystems: metabolism, compartmentalization, and information. A specific model for the prebiological evolution of a reproducing system with rudimentary versions of these three interdependent subsystems is presented. This is based on the initial emergence and reproduction of autocatalytic networks in hydrothermal microcompartments containing iron sulfide. The driving force for life was catalysis of the dissipation of the intrinsic redox gradient of the planet. The codependence of life on iron and phosphate provides chemical constraints on the ordering of prebiological evolution. The initial protometabolism was based on positive feedback loops associated with in situ carbon fixation in which the initial protometabolites modified the catalytic capacity and mobility of metal-based catalysts, especially iron-sulfur centers. A number of selection mechanisms, including catalytic efficiency and specificity, hydrolytic stability, and selective solubilization, are proposed as key determinants for autocatalytic reproduction exploited in protometabolic evolution. This evolutionary process led from autocatalytic networks within preexisting compartments to discrete, reproducing, mobile vesicular protocells with the capacity to use soluble sugar phosphates and hence the opportunity to develop nucleic acids. Fidelity of information transfer in the reproduction of these increasingly complex autocatalytic networks is a key selection pressure in prebiological evolution that eventually leads to the selection of nucleic acids as a digital information subsystem and hence the emergence of fully functional chemotons capable of Darwinian evolution. 1 Introduction: Chemoton Subsystems and Evolutionary Pathways Living cells are autocatalytic entities that harness redox energy via the selective catalysis of biochemical transformations. -
Quasispecies Theory in Virology
JOURNAL OF VIROLOGY, Jan. 2002, p. 463–465 Vol. 76, No. 1 0022-538X/02/$04.00ϩ0 DOI: 10.1128/JVI.76.1.463–465.2002 Copyright © 2002, American Society for Microbiology. All Rights Reserved. Quasispecies Theory in Virology Holmes and Moya claim that quasispecies is an unnecessary ular sort. Darwinian principles in connection with quasispecies and misleading description of RNA virus evolution, that virol- have been explicitly invoked by theoreticians and experimen- ogists refer to quasispecies inappropriately, and that there is talists alike (11, 13, 16, 35). little evidence of quasispecies in RNA virus evolution. They What is the evidence of quasispecies dynamics in RNA virus wish to look for other ideas in evolutionary biology and to set populations, and why is quasispecies theory exerting an influ- down an agenda for future research. I argue here that real virus ence in virology? The initial experiment with phage Q which quasispecies often differ from the theoretical quasispecies as provided the first experimental support for a quasispecies dy- initially formulated and that this difference does not invalidate namics in an RNA virus (14, 17) has now been carried out with quasispecies as a suitable theoretical framework to understand biological and molecular clones of representatives of the major viruses at the population level. groups of human, animal, and plant RNA viruses, including In the initial theoretical formulation to describe error-prone immunodeficiency viruses and hepatitis C virus, both in cell replication of simple RNA (or RNA-like) molecules, quasispe- culture and in vivo (11). Support for quasispecies has also cies were defined as stationary (equilibrium) mutant distribu- come from studies on replication of RNA molecules in vitro tions of infinite size, centered around one or several master (4). -
Dynamics of a Discrete Hypercycle
Treball final de grau GRAU DE MATEMÀTIQUES Facultat de Matemàtiques i Informàtica Universitat de Barcelona Dynamics of a Discrete Hypercycle Autor: Júlia Perona García Directors: Dr. Ernest Fontich, Dr. Josep Sardanyés Realitzat a: Departament de Matemàtiques i Informàtica Barcelona, June 27, 2018 Abstract The concept of the Hypercycle was introduced in 1977 by Manfred Eigen and Peter Schuster within the framework of origins of life and prebiotic evolution. Hypercycle are catalytic sets of macromolecules, where each replicator catalyzes the replication of the next species of the set. This system was proposed as a possible solution to the information crisis in prebiotic evolution. Hypercycles are cooperative systems that allow replicators to increase their information content beyond the error threshold. This project studies the dynamics of a discrete-time model of the hypercycle consider- ing heterocatalytic interactions. To date, hypercycles’ dynamics has been mainly studied using continuous-time dynamical systems. We follow the Hofbauer’s discrete model [13]. First, we introduce some important and necessary mathematical notions. Then, we also review the biological concept of the hypercycle and some criticisms that it has received. We present a complete proof of the fact that the hypercycle is a cooperative system. Also, we present an analytic study of the fixed point in any dimension and its stability. In particular, in dimension three we prove that fixed point is globally asymptotically stable. In dimension four we have obtained a stable invariant curve for all values of the discreteness parameter. 2010 Mathematics Subject Classification. 37C05, 37N25 Acknowledgements I would like to thank my directors, Ernest and Josep, to support me throughout this project. -
The Molecular Underpinnings of Genetic Phenomena
Heredity (2008) 100, 6–12 & 2008 Nature Publishing Group All rights reserved 0018-067X/08 $30.00 www.nature.com/hdy SHORT REVIEW The molecular underpinnings of genetic phenomena N Lehman Department of Chemistry, Portland State University, Portland, OR, USA Epiphenomena are those processes that ostensibly have no whole organisms and populations may have their ultimate precedent at lower levels of scientific organization. In this evolutionary roots in the chemical repertoire of catalytic review, it is argued that many genetic processes, including RNAs. Some of these phenomena will eventually prove to be ploidy, dominance, heritability, pleiotropy, epistasis, muta- not only analogous but homologous to ribozyme activities. tional load and recombination, all are at least analogous to Heredity (2008) 100, 6–12; doi:10.1038/sj.hdy.6801053; biochemical events that were requisite features of the RNA published online 29 August 2007 world. Most, if not all, of these features of contemporary Keywords: RNA; ploidy; pleiotropy; epistasis; heritability; recombination Introduction Below are discussed seven well-known genetic pro- cesses for which a clear molecular basis can be The history of life, if traced with perfect detail, would postulated. By ‘molecular basis’ it is meant that a reveal a long and gradual expansion of networks of chemical property of biopolymers, usually RNA, can be chemical reactions. If viewed in less detail, a series of identified as a direct forbearer of the higher-order plateaus would be seen, each representing a discrete property observed in whole organisms. Again, an advancement in complexity (Fontana and Schuster, 1998; important aspect of this is the idea that many of these Hazen et al., 2007). -
Error Propagation in the Hypercycle
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by CERN Document Server Error propagation in the hypercycle P. R. A. Campos and J. F. Fontanari Instituto de F´ısica de S˜ao Carlos, Universidade de S˜ao Paulo Caixa Postal 369, 13560-970 S˜ao Carlos SP, Brazil P. F. Stadler Institut f¨ur Theorestische Chemie, Universit¨at Wien W¨ahringerstraße 17, A-1090 Wien, Austria The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe NM 87501, USA some pathological, discontinuous replication landscapes We study analytically the steady-state regime of a net- [4], the coexistence problem seems to be more pervasive, work of n error-prone self-replicating templates forming an as it is associated to the form of the growth functions in asymmetric hypercycle and its error tail. We show that the the chemical kinetics equations [5,6]. existence of a master template with a higher non-catalyzed In order to circumvent the aforementioned limitations self-replicative productivity, a, than the error tail ensures the of the quasispecies model, Eigen and Schuster proposed stability of chains in which m<n 1 templates coexist with the master species. The stability of− these chains against the the hypercycle [7], that is, a catalytic feedback network error tail is guaranteed for catalytic coupling strengths (K) whereby each template helps in the replication of the next of order of a. We find that the hypercycle becomes more sta- one, in a regulatory cycle closing on itself. This model ble than the chains only for K of order of a2. -
Full Analysis of Small Hypercycles with Short-Circuits in Prebiotic Evolution
Full Analysis of Small Hypercycles with Short-circuits in Prebiotic Evolution Josep Sardany´es,1, 2, ∗ J. Tom´asL´azaro,3, 4 Toni Guillamon,4, 5 and Ernest Fontich4, 6 1ICREA-Complex Systems Lab, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain 2Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Passeig Mar´ıtim de la Barceloneta 37, 08003 Barcelona, Spain 3Departament de Matem`atiques,Av. Diagonal, 647 (Universitat Polit`ecnica de Catalunya) 08028, Barcelona, Spain 4Barcelona Graduate School of Mathematics BGSMath 5Departament de Matem`atiques,Av. Gregorio Mara~n´on44-50 (Universitat Polit`ecnica de Catalunya) 08028, Barcelona, Spain 6Departament de Matem`atiquesi Inform`atica (Universitat de Barcelona), Gran Via de les Corts Catalanes 585, 08007 Barcelona, Spain (Dated: November 25, 2016) It is known that hypercycles are sensitive to the so-called parasites and short-circuits. While the impact of parasites has been widely investigated for well-mixed and spatial hypercycles, the effect of short-circuits in hypercycles remains poorly understood. In this article we analyze the mean field and spatial dynamics of two small, asymmetric hypercycles with short-circuits. Specifically, we analyze a two-member hypercycle where one of the species contains an autocatalytic loop, as the simplest hypercycle with a short-circuit. Then, we extend this system by adding another species that closes a three-member hypercycle while keeping the autocatalytic short-circuit and the two-member cycle. The mean field model allows us to discard the presence of stable or unstable periodic orbits for both systems. We characterize the bifurcations and transitions involved in the dominance of the short-circuits i.e., in the reduction of the hypercycles' size. -
Viral Quasispecies Reconstruction Using Next Generation Sequencing Reads
Georgia State University ScholarWorks @ Georgia State University Computer Science Dissertations Department of Computer Science Summer 8-12-2013 Viral Quasispecies Reconstruction Using Next Generation Sequencing Reads Bassam A. Tork Georgia State University Follow this and additional works at: https://scholarworks.gsu.edu/cs_diss Recommended Citation Tork, Bassam A., "Viral Quasispecies Reconstruction Using Next Generation Sequencing Reads." Dissertation, Georgia State University, 2013. https://scholarworks.gsu.edu/cs_diss/77 This Dissertation is brought to you for free and open access by the Department of Computer Science at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Computer Science Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. VIRAL QUASISPECIES RECONSTRUCTION USING NEXT GENERATION SEQUENCING READS by BASSAM TORK Under the Direction of Dr. Alexander Zelikovsky ABSTRACT The genomic diversity of viral quasispecies is a subject of great interest, especially for chronic infections. Characterization of viral diversity can be addressed by high-throughput sequencing technology (454 Life Sciences, Illumina, SOLiD, Ion Torrent, etc.). Standard assembly software was originally designed for single genome assembly and cannot be used to assemble and estimate the frequency of closely related quasispecies sequences. This work focuses on parsimonious and maximum likelihood models for assembling viral quasispecies -
Statistical Properties and Error Threshold of Quasispecies on Single-Peak Gaussian-Distributed Fitness Landscapes
Statistical properties and error threshold of quasispecies on single-peak Gaussian-distributed fitness landscapes Duo-Fang Li a, Tian-Guang Cao a, Jin-Peng Geng a, Jian-Zhong Gu b, Hai-Long Ana,Yong Zhan a* a Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China b China Institute of Atomic Energy, P. O. Box 275 (10), Beijing 102413, China Abstract: The stochastic Eigen model proposed by Feng et al. (Journal of theoretical biology, 246 (2007) 28) showed that error threshold is no longer a phase transition point but a crossover region whose width depends on the strength of the random fluctuation in an environment. The underlying cause of this phenomenon has not yet been well examined. In this article, we adopt a single peak Gaussian distributed fitness landscape instead of a constant one to investigate and analyze the change of the error threshold and the statistical property of the quasi-species population. We find a roughly linear relation between the width of the error threshold and the fitness fluctuation strength. For a given quasi-species, the fluctuation of the relative concentration has a minimum with a normal distribution of the relative concentration at the maximum of the averaged relative concentration, it has however a largest value with a bimodal distribution of the relative concentration near the error threshold. The above results deepen our understanding of the quasispecies and error threshold and are heuristic for exploring practicable antiviral strategies. Keywords: quasispecies; error threshold; single peak fitness; Gaussian distribution; randomization 1. Introduction The researches on the species evolution have been a focus for a long time. -
Viruses at the Edge of Adaptation
Virology 270, 251–253 (2000) doi:10.1006/viro.2000.0320, available online at http://www.idealibrary.com on MINIREVIEW Viruses at the Edge of Adaptation Esteban Domingo1 Centro de Biologı´a Molecular “Severo Ochoa,” (CSIC-UAM) Universidad Auto´noma de Madrid, Cantoblanco, 28049 Madrid, Spain Received February 25, 2000; accepted March 14, 2000 How vulnerable is the line that separates adaptation from extinction? Viruses, in particular RNA viruses, are well known for their high rates of genetic variation and their potential to adapt to environmental modifications (Drake and Holland, 1999; Domingo et al., 2000). Yet, fitness variations—both increases and decreases—can be spectacularly rapid, and the simple genetic stratagem of forcing virus multiplication to go through repeated genetic bottlenecks can induce fitness losses, at times near viral extinction. New information has been recently obtained on the two sides of the survival line: the edge of adaptation and the edge of extinction. © 2000 Academic Press SUBTLE ADAPTIVE STRATEGIES present in the population. Furthermore, this particular variant was systematically selected, while, when absent RNA virus quasispecies are highly effective in the from memory, its selection was rare (Ruiz-Jarabo et al., exploration of new genomic sequences (Eigen and 2000). In agreement with the concept that memory ge- Biebricher, 1988). It has long been known that mutant nomes are part of the mutant spectrum of the quasispe- swarms (the mutant spectra that populate viral quasispe- cies, memory was erased when the populations were cies) contain potentially useful variants [those with in- subjected to genetic bottlenecks (Fig. 1). Because of the creased resistance to antiviral agents, altered interferon- existence of a molecular memory, a viral quasispecies inducing capacity, or antibody-escape and cytotoxic T may be capable of reacting swiftly to a selective con- lymphocyte (CTL)-escape mutants, among others]. -
The Self-Organization of Cyberprotest
The Internet Society II: Advances in Education, Commerce & Governance 275 The self-organization of cyberprotest C. Fuchs ICT&S Center, Advanced Studies and Research in Information and Communication Technologies & Society, University of Salzburg, Austria Abstract The specific task of this paper is to describe cyberprotest as a self-organizing system. Cyberprotest is a global structural coupling and mutual production of self-organization processes of the Internet and self-organization processes of the protest system of society. In cyberprotest the self-organization of the Internet system and the self-organization of the protest system produce each other mutually in a self-organization process, hence cyberprotest is a self-organization of self-organization processes, a form of second-order self-organization Keywords: cyberprotest, self-organization, complexity, online activism, social movements. 1 Introduction Cyberspace is a global technologically mediated space of cognition, communication, and co-operation, a sphere of production, reproduction, and circulation of human knowledge. It is inherently networked, decentralized, and dynamic. Besides being a big marketplace, it is also a medium of political interaction. This paper attempts to describe the phenomenon of cyberprotest at a theoretical level. Cyberprotest is an emerging field of social movement research that reflects the role of alternative online media, online protests, and online protest communication in society [cf. 1, 3, 19, 31, 32, 33, 39, 40, 42, 46, 48]. The existing approaches are mainly descriptive and empirical, what is missing is a broader theoretical perspective that embeds the phenomenon of cyberprotest into social theory and provides theoretical concepts that can guide research. This paper tries to make a contribution to the establishment of theoretical foundations of cyberprotest by considering the latter within the perspective of self- organization theory. -
Evolutionary Virology at 40
| PERSPECTIVES Evolutionary Virology at 40 Jemma L. Geoghegan* and Edward C. Holmes†,‡,§,**,1 *Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia and †Marie Bashir Institute for Infectious Diseases and Biosecurity, ‡Charles Perkins Centre, §School of Life and Environmental Sciences, and **Sydney Medical School, The University of Sydney, New South Wales 2006, Australia ORCID IDs: 0000-0003-0970-0153 (J.L.G.); 0000-0001-9596-3552 (E.C.H.) ABSTRACT RNA viruses are diverse, abundant, and rapidly evolving. Genetic data have been generated from virus populations since the late 1970s and used to understand their evolution, emergence, and spread, culminating in the generation and analysis of many thousands of viral genome sequences. Despite this wealth of data, evolutionary genetics has played a surprisingly small role in our understanding of virus evolution. Instead, studies of RNA virus evolution have been dominated by two very different perspectives, the experimental and the comparative, that have largely been conducted independently and sometimes antagonistically. Here, we review the insights that these two approaches have provided over the last 40 years. We show that experimental approaches using in vitro and in vivo laboratory models are largely focused on short-term intrahost evolutionary mechanisms, and may not always be relevant to natural systems. In contrast, the comparative approach relies on the phylogenetic analysis of natural virus populations, usually considering data collected over multiple cycles of virus–host transmission, but is divorced from the causative evolutionary processes. To truly understand RNA virus evolution it is necessary to meld experimental and comparative approaches within a single evolutionary genetic framework, and to link viral evolution at the intrahost scale with that which occurs over both epidemiological and geological timescales. -
The Hypercycle
The Hypercycle A Principle of Natural Self-Organization Part B" The Abstract Hypercycle Manfred Eigen Max-Planck-Institut fiir biophysikalische Chemie, D-3400 G6ttingen Peter Schuster Institut fiir theoretische Chemie und Strahlenchemie der Universit~it, A-1090 Wien Topologic methods are used to characterize a particu- necessary to reach a stable information content of a few lar class of self-replicative reaction networks: the thousand nucleotides. Such an amount would be just hypercycles. The results show that the properties of sufficient to code for a few protein molecules, as we find hypercycles are sufficient for a stable integration of the in present RNA phages. The physical properties in- information contained in several self-replicative units. herent in the nucleic acids allow for a reproducible Among the catalytic networks studied, hypercyclic accumulation of information of no more than 50 to 100 organization proves to be a necessary prerequisite for nucleotides. maintaining the stability of information and for pro- The last of these three statements may be questioned on moting its further evolution. The techniques used in the basis of the argument that environmental factors this paper, though familiar to mathematicians, are -such as suitable catalytic surfaces or even protein- introduced in detail in order to make the logical like enzyme precursors [47]-may cause a consider- arguments accessible to the nonmathematician. able shift of those numbers. In fact, the figures given were derived from equilibrium data, namely, from the free energies for (cooperative) complementary versus noncomplementary nucleotide interactions. Neverthe- V. The Concrete Problem less, we still consider them upper limits which in nature may actually be reached only in the presence of suitable In Part A of this trilogy on hypercycles we have arrived catalysts or via annealing procedures.