DOCSLIB.ORG

Exact Solution of the Eigen Model with General Fitness Functions and Degradation Rates

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Exact Solution of the Eigen Model with General Fitness Functions and Degradation Rates Exact solution of the Eigen model with general fitness functions and degradation rates David B. Saakian*† and Chin-Kun Hu*‡ *Institute of Physics, Academia Sinica, Nankang, Taipei 11529, Taiwan; and †Yerevan Physics Institute, Alikhanian Brothers Street 2, Yerevan 375036, Armenia Edited by H. Eugene Stanley, Boston University, Boston, MA, and approved January 18, 2006 (received for review June 13, 2005) We present an exact solution of Eigen’s quasispecies model with a the spins can take four values corresponding to the natural general degradation rate and fitness functions, including a square nucleotide types, but a two-value spin model already catches the root decrease of fitness with increasing Hamming distance from essential features and can be studied more easily. Two-value spin the wild type. The found behavior of the model with a degradation models also have been used to study long-range correlations in rate is analogous to a viral quasispecies under attack by the DNA sequences (17) and DNA unzipping (18, 19), and valuable immune system of the host. Our exact solutions also revise the results have been obtained. A generalization of our results for known results of neutral networks in quasispecies theory. To the four-value spin case is presented in the Supporting Text, which explain the existence of mutants with large Hamming distances is published as supporting information on the PNAS website. from the wild type, we propose three different modifications of However, such results include more cumbersome formula, and the Eigen model: mutation landscape, multiple adjacent mutations, from now on we will only consider the two-value spin model. and frequency-dependent fitness in which the steady-state solu- Let sj ϭϩ1 represent purines (R) and sj ϭϪ1 pyrimidines ϵ (i) (i) (i) tion shows a multicenter behavior. (Y). Type i is then specified by Si (s1 , s2 ,..., sN ). The model describes replicating molecules under control of variation quasispecies ͉ virus evolution ͉ error threshold and natural selection with Eq. 1, to be defined below. The rate coefficients of replication and mutation are assumed to be olecular models of biological evolution have attracted independent of the concentration of the types. The model BIOPHYSICS Mmuch attention in recent decades (1–15). Among them, describes the exponential growth phase of virus evolution, in Eigen’s concept of quasispecies plays a fundamental role (1, 2). which there are enough nutrients and low virus concentration. It describes the evolution of a population consisting of a wild The multistep cross-catalytic reactions are replaced by an auto- type accompanied by a large number of mutant types in se- catalytic one. Here the evolution picture is rather simple, quence space by a large system of ordinary differential equa- compared with the linear growth phase in the case of strong tions. The Eigen model has been found to describe quite well the saturation effects. evolution of viral populations (3) and has deeply changed our Selection is on a genotype level: fitness is a function of Si. The view of the process of evolution: adaptation does not wait for variation is assumed to be produced only by point mutations. better adapted mutants to arise but starts with the selection of Eigen made a deterministic approach with kinetic rate equations the better adapted mutants and then explores by mutation the that requires an infinite population, whereas classical population surrounding sequence space for even better mutants. When the genetics uses probabilistic equations. We denote the probability for the appearance of S at time t by p ϵ p (t) and define fitness mutation rate surpasses an error threshold, the population gets i Si i r S genetically unstable, and it could be shown that indeed virus i of i as the average number of offsprings produced per unit time and degradation rate D of S as an inverse mean longevity. populations can be driven to extinction when the error rate is i i The chosen r and D are functions in genome sequence space S , artificially raised beyond the error threshold. i i i i.e., r ϭ f(S ) and D ϭ D(S ). To describe the population precisely, we should know the i i i i The mutation matrix element Q is the probability that an fitness value of each type and the mutation rates to go from one ij offspring produced by state j changes to state i, and the evolution type to another. The experimental efforts to do so are immense. is given by the set of equations for 2N probabilities p (2, 6) During the last three decades, the model has been investigated i numerically as well as analytically for a simple fitness function. 2N 2N Although this sort of data reduction does allow a view on a large dpi ϭ ͸ ͓Q r Ϫ ␦ D ͔p Ϫ p ͩ͸͑r Ϫ D ͒p ͪ. [1] population, the fitness functions chosen are too simplistic to dt ij j ij j j i j j j ϭ ϭ explain realistic cases such as a population of RNA virus. In this j 1 j 1 work, we solve the system of differential equations exactly, ͚2N ϭ ϭ NϪd(i,j) Ϫ d(i,j) Here pi satisfies iϭ1 pi 1 and Qij q (1 q) with assuming uniform degradation rates and fitness functions in- q being the mean nucleotide incorporation fidelity, and d(i, j) ϵ cluding a square root decrease of fitness with increasing Ham- N (i) (j) (N Ϫ͚ϭ s s )͞2 being the HD between Si and Sj (1, 2); d(i, j) ming distance (HD) from the wild type. Our exact solutions also l 1 l l represents the total number of different spin values in Si and Sj. revise the known theoretical results of neutral networks in In ref. 1 the concept of an error threshold is introduced, and quasispecies theory (2). To explain biological systems more the error threshold has been quantified by a formula. For the realistically (16), we propose three different modifications of the calculation of the error threshold, the selection values and Eigen model: mutation landscape, multiple adjacent mutations, mutation rates of all types would be required, which is still not and frequency-dependent fitness in which the steady-state so- lution shows a multicenter behavior. Conflict of interest statement: No conflicts declared. Model This paper was submitted directly (Track II) to the PNAS office. Several excellent reviews (2–5) emphasize the merits of the Abbreviations: AS, antiselective; FM, ferromagnetic; HD, Hamming distance; PM, quasispecies model for the interpretation of virological studies. paramagnetic. Let us give a brief description of the quasispecies model as we ‡To whom correspondence should be sent at the * address. E-mail: [email protected]. use it in this work: a sequence type of length N is specified by a edu.tw. sequence of N spin values sk ϭϮ1, 1 Յ k Յ N (1, 2). In reality © 2006 by The National Academy of Sciences of the USA www.pnas.org͞cgi͞doi͞10.1073͞pnas.0504924103 PNAS ͉ March 28, 2006 ͉ vol. 103 ͉ no. 13 ͉ 4935–4939 Downloaded by guest on September 24, 2021 feasible. For data reduction, several fitness functions (land- obtained. Eigen introduced AeϪ␥ as a ‘‘selective value’’ of the scapes) have been considered (2). The simplest one has a single peak (equation II-31 in ref. 1). In case of several isolated peaks peak (2) in a flat landscape. Without loss of generality we set the the system chooses the one with the maximal selective value. peak to S1 ϵ (1, 1, . , 1), i.e., the state with all spin up, and have Case 2: Single Peak Fitness Function with Degradation. Consider nonzero degradation d (k) ϭ c ϩ ␣k, where the positive number ͑ ͒ ϭ Ͼ ͑ ͒ ϭ 0 f S1 A 1, and f Si 1 for Si S1, [2] ␣ Ͼ 0 is the degradation parameter, and the same fitness function as in case 1. Physically, d0(k) should be always positive for any for which Eigen error threshold formula (equation II-45 in ref. Ͼ ␣ 1) gives an exact result value of k and we take c . Because of symmetry of Eigen’s equations under the transformation Di 3 Di ϩ C with C being Ϫ␥ Ae Ͼ 1, [3] a constant, we can simply choose d0(k) ϭ ␣k, which will be used in the following discussion. Now we have the PM phase with k ϭ ␥ ϭ for successful selection (p. 180 in ref. 2). The parameter 0 and ln Z͞␤ ϭ 1 ϵ WPM, the FM phase with k ϭ 1 and N(1 Ϫ q) describes the mutation efficiency. When the inequality is satisfied, a mutant distribution is built around the peak ln Z ϭ Ϫ␥ Ϫ ␣ ϵ ͑ ͒ configuration in the steady state. Otherwise the distribution is ␤ Ae WFM k . [7] flat in the infinite genome length limit, i.e., no sequence is preferred [error catastrophe (1, 2)]. Besides these phases, we also have the antiselective (AS) phase, We consider general fitness function f(Si) and degradation which can be located by finding the maximum of D(Si), which depend on the HD (the number of nucleotide differences between two sequences) from the peak configuration ln Z ͱ ϭ ͓ Ϫ␥͑1Ϫ 1Ϫk2͒ Ϫ ␣ ͔ ϵ ͑ ͒ e k WAS k , [8] S1. In statistical physics this case corresponds to mean-field-like ␤ interaction, which is exactly solvable (20). We can write f(Si) and D(Si) as (6) in the interval Ϫ1 Յ k Յ 1. To find the maximum we should take the value of Eq.
Load more

Recommended publications
  • 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).
    [Show full text]
  • 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
    [Show full text]
  • 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].
    [Show full text]
  • 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.
    [Show full text]
  • Error Threshold in RNA Quasispecies Models with Complementation
    ARTICLE IN PRESS Journal of Theoretical Biology 265 (2010) 278–286 Contents lists available at ScienceDirect Journal of Theoretical Biology journal homepage: www.elsevier.com/locate/yjtbi Error threshold in RNA quasispecies models with complementation Josep Sardanye´s a,Ã, Santiago F. Elena a,b a Instituto de Biologı´a Molecular y Celular de Plantas, Consejo Superior de Investigaciones Cientı´ficas-UPV, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain b Santa Fe Institute, 1399 Hyde Park Road, Santa Fe NM 87501, USA article info abstract Article history: A general assumption of quasispecies models of replicons dynamics is that the fitness of a genotype is Received 22 December 2009 entirely determined by its sequence. However, a more biologically plausible situation is that fitness Received in revised form depends on the proteins that catalyze metabolic reactions, including replication. In a stirred population 26 April 2010 of replicons, such as viruses replicating and accumulating within the same cell, the association between Accepted 14 May 2010 a given genome and the proteins it encodes is not tight as it can be replicated by proteins translated Available online 21 May 2010 from other genomes. We have investigated how this complementation phenomenon affects the error Keywords: threshold in simple quasispecies mean field models. We first studied a model in which the master and Complementation the mutant genomes code for wild-type and mutant replicases, respectively. We assume that the Defective interfering particles mutant replicase has a reduced activity and that the wild-type replicase does not have increased affinity Error threshold for the master genome.
    [Show full text]
  • Profiling SARS-Cov-2 Mutation Fingerprints That Range from the Viral Pangenome to Individual Infection Quasispecies Billy T
    Lau et al. Genome Medicine (2021) 13:62 https://doi.org/10.1186/s13073-021-00882-2 RESEARCH Open Access Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies Billy T. Lau1,2†, Dmitri Pavlichin1†, Anna C. Hooker1†, Alison Almeda1, Giwon Shin1, Jiamin Chen1, Malaya K. Sahoo3, Chun Hong Huang3, Benjamin A. Pinsky3,4, Ho Joon Lee1* and Hanlee P. Ji1,2* Abstract Background: The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contact tracing. Methods: Leveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies variants, and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints. Results: We built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes.
    [Show full text]
  • Virus-Host Interactions by Linking Virology and Bioinformatics
    viruses Commentary ITN—VIROINF: Understanding (Harmful) Virus-Host Interactions by Linking Virology and Bioinformatics Winfried Goettsch 1 , Niko Beerenwinkel 2,† , Li Deng 3,† , Lars Dölken 4,† , Bas E. Dutilh 5,† , Florian Erhard 4,† , Lars Kaderali 6,† , Max von Kleist 7,†, Roland Marquet 8 , Jelle Matthijnssens 9,† , Shawna McCallin 10 , Dino McMahon 11,† , Thomas Rattei 12 , Ronald P. Van Rij 13,† , David L. Robertson 14,† , Martin Schwemmle 15,† , Noam Stern-Ginossar 16 and Manja Marz 1,17,*,† 1 RNA Bioinformatics and High-Throughput Analysis, Friedrich Schiller University, 07743 Jena, Germany; [email protected] 2 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; [email protected] 3 Institute of Virology, Helmholtz Centre Munich and Technical University Munich, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany; [email protected] 4 Institut für Virologie und Immunbiologie, Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany; [email protected] (L.D.); fl[email protected] (F.E.) 5 Theoretical Biology and Bioinformatics, Science for Life, Utrecht University, Hugo R. Kruytgebouw, Padualaan 8, 3584 CH Utrecht, The Netherlands; [email protected] 6 Institute of Bioinformatics, University Medicine Greifswald, 17475 Greifswald, Germany; [email protected] 7 MF1 Bioinformatics, Robert Koch-Institute, 13353 Berlin, Germany; [email protected] 8 CNRS, Architecture et Réactivité de l’ARN, Université de
    [Show full text]
  • Qcolors: an Algorithm for Conservative Viral Quasispecies Reconstruction from Short and Non-Contiguous Next Generation Sequencing Reads
    2011 IEEE International Conference on Bioinformatics and Biomedicine Workshops QColors: An Algorithm for Conservative Viral Quasispecies Reconstruction from Short and Non-Contiguous Next Generation Sequencing Reads Austin Huang∗, Rami Kantor∗, Allison DeLong†, Leeann Schreier∗, and Sorin Istrail‡ ∗ Division of Infectious Disease, † Center for Statistical Sciences, ‡ Department of Computer Science, Brown University Providence, RI, USA, Email: [email protected] Abstract—Next generation sequencing technologies have been viral population that consists of genetically distinct subpopu- successfully applied to HIV-infected patients in order to obtain lations [12]–[14]. Thus the viral population is often described the mutational spectrum of heterogeneous viral populations as a quasispecies [15]. Viral populations that circulate at low within individuals, known as quasispecies. However, the metage- nomics problem of quasispecies sequence reconstruction from levels, termed minor variants, are clinically relevent because next generation sequencing reads is not-yet widely applied in drug-resistant subpopulations may be selected upon treatment current practice and remains an emerging area of research. [16]–[18]. These minor variants are often undetectable using Furthermore, the majority of research methodology in HIV standard sequencing protocols. Specialized techniques such has focused on 454 sequencing, while many next-generation as clonal and single genome sequencing (SGS) have been sequencing platforms are limited to shorter read lengths relative to 454 sequencing. Little work has been done in determining how developed to obtain sequences of minor variant subpopulations best to address the read length limitations of other platforms. within patients [19]–[22]. SGS, in particular, was designed to The approach described here incorporates graph representa- address and minimize sequencing artifacts such as recombi- tions of both read differences and read overlap to conservatively nation of qusispecies sequences during PCR [19].
    [Show full text]
  • The Impact of Quasispecies Dynamics on the Use of Therapeutics
    Review The impact of quasispecies dynamics on the use of therapeutics 1,2 3 3 1,2,3 Celia Perales , Jaime Iranzo , Susanna C. Manrubia , and Esteban Domingo 1 Centro de Biologı´a Molecular ‘‘Severo Ochoa’’ (CSIC-UAM), Campus de Cantoblanco 28049, Madrid, Spain 2 Centro de Investigacio´ n Biome´ dica en Red de Enfermedades Hepa´ ticas y Digestivas (CIBERehd), 08036 Barcelona, Spain 3 Centro de Astrobiologı´a (INTA-CSIC), Instituto Nacional de Te´ cnica Aeroespacial, Carretera de Ajalvir km 4, 28850 Torrejo´ n de Ardoz, Madrid, Spain The application of quasispecies theory to viral popula- Glossary tions has boosted our understanding of how endoge- Combination therapy: treatment that consists of the administration of two or nous and exogenous features condition their adaptation. more drugs. Mounting empirical evidence demonstrates that internal Complementation: increase of viral progeny production mediated by gene interactions within mutant spectra may cause unexpect- products supplied by another virus (in quasispecies, supplied by closely related variants). ed responses to antiviral treatments. In this scenario, Complexity of a mutant spectrum: number of mutations and genomic increased mutagenesis could be efficient at low muta- sequences in a viral population. It is often quantified by pairwise genetic gen doses due to the lethal action of defective genomes, distances, mutation frequency (calculated by dividing the number of different mutations by the total number of nucleotides sequenced), and Shannon whereas sequential administration of antiviral drugs entropy (proportion of different genomes in the population). New technologies might be superior to combination therapies. Our ability should allow a quantitative characterization of quasispecies complexity in to predict the outcome of a particular therapy takes terms of phenotypic diversity.
    [Show full text]
  • Viral Evolution and the Emergence of SARS Coronavirus
    FirstCite Published online e-publishing Viral evolution and the emergence of SARS coronavirus Edward C. Holmes* and Andrew Rambaut Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK The recent appearance of severe acute respiratory syndrome coronavirus (SARS-CoV) highlights the con- tinual threat to human health posed by emerging viruses. However, the central processes in the evolution of emerging viruses are unclear, particularly the selection pressures faced by viruses in new host species. We outline some of the key evolutionary genetic aspects of viral emergence. We emphasize that, although the high mutation rates of RNA viruses provide them with great adaptability and explain why they are the main cause of emerging diseases, their limited genome size means that they are also subject to major evolutionary constraints. Understanding the mechanistic basis of these constraints, particularly the roles played by epistasis and pleiotropy, is likely to be central in explaining why some RNA viruses are more able than others to cross species boundaries. Viral genetic factors have also been implicated in the emergence of SARS-CoV, with the suggestion that this virus is a recombinant between mammalian and avian corona- viruses. We show, however, that the phylogenetic patterns cited as evidence for recombination are more probably caused by a variation in substitution rate among lineages and that recombination is unlikely to explain the appearance of SARS in humans. Keywords: emerging viruses; SARS coronavirus; evolution; phylogeny; recombination 1. INTRODUCTION relatives in Himalayan palm civets (Guan et al. 2003), although it is not yet established that these are the source Since the first descriptions of AIDS in the early 1980s, population for the human form of the virus.
    [Show full text]
  • SARS-Cov-2 Quasispecies Provides Insight Into Its Genetic Dynamics During Infection
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.20.258376; this version posted August 20, 2020. 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-ND 4.0 International license. SARS-CoV-2 Quasispecies provides insight into its genetic dynamics during infection Fengming Sun1,4,#, Xiuhua Wang1,4,#, Shun Tan2,#, Yunjie Dan1,4, Yanqiu Lu2, Juan Zhang1,4, Junli Xu3, Zhaoxia Tan1, Xiaomei Xiang1, Yi Zhou1, Weiwei He1, Xing Wan1, Wei Zhang1, Yaokai Chen2,*, Wenting Tan1,4,*, Guohong Deng1,4,* 1 Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China; 2 Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing 400036, China; 3 Beijing Novogene Company Limited, Beijing 100015, China; 4 Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China. # Authors contributed equally to this article *Corresponding Author: (1) Guohong Deng, PhD, Army Medial University, Southwest Hospital, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China, Email:[email protected]; (2) Wenting Tan, PhD, Army Medial University, Southwest Hospital, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Email: [email protected]; (3) Yaokai Chen, PhD, Chongqing Public Health Medical Center, 109 Baoyu Road, Shapingba District, Chongqing 400036, China, Email: [email protected]. 1 / 28 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.20.258376; this version posted August 20, 2020. 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.
    [Show full text]
  • QUASISPECIES and VIRUS EVOLUTION Esteban
    Gene Therapy (2001) 8, (Suppl 1), S1–S13 2001 Nature Publishing Group All rights reserved 0969-7128/01 $15.00 www.nature.com/gt QUASISPECIES AND VIRUS EVOLUTION PANDEMIC SPREAD: INFLUENZA Robert G. Webster1•2, Yi Guan2, Scott Krauss1, Kennedy Esteban Domingo Shortridge2, Malik Peiris2 Centro de Biologfa Molecular "Severo Ochoa" 1) Dept. Virol Mo! Biol, St. Jude C R Hosp., 332 N. (CSIC-UAM). Cantoblanco, 28049 Madrid, Spain Lauderdale, Memphis, Tennessee, and 2) Dept Microbiol, Hong Kong Univ., SAR China High mutation rates and quasispecies dynamics are a Influenza virus continues to evolve, and new antigenic drift hallmark of RNA viruses. Recent studies with foot-and­ variants emerge constantly, giving rise to yearly epidemics. In mouth disease virus (FMDV) have revealed rapid addition, strains to which most humans have no immunity coevolution of antigenicity and host cell tropism of virus appear suddenly, and the resulting pandemics vary from populations in cell culture and in vivo. Remarkable serious to catastrophic. Studies in aquatic birds over 25 years expansions of host cell tropism occurred in a clonal have established that they play an important role in the natural population of FMDV as a result of prolonged cytolytic history of influenza viruses. In the past four years there have replication in BHK-21 cells. Reversion of mutants with been two different transmissions of avian influenza viruses to humans in Hong Kong. The first genetic lesions associated with decreases in viral fitness, occurred in 1997, when 6 of 18 infected humans died of H5Nl influenza virus. In March and analysis of the mutant spectra of revertant 1999, H9N2 influenza viruses were isolated from two children populations, have indicated the presence of memory in Hong Kong and unconfirmed reports of an additional five genomes in viral quasispecies.
    [Show full text]