Genomic Flux: Genome Evolution by Gene Loss and Acqibsition

Total Page:16

File Type:pdf, Size:1020Kb

Genomic Flux: Genome Evolution by Gene Loss and Acqibsition GENOMIC FLUX: GENOME EVOLUTION BY GENE LOSS AND ACQIBSITION Jeffrey G. LAwrence and John R. Roth 15 Genome evolution is the process by which the introduction of mitochondria and chloro­ content and organization of a species' genetic plasts). In bacteria, however, both genetics and information changes over time. This process genome analysis provide extensive evidence involves four sorts of changes: (i) point mu­ for gene loss and horizontal genetic transfer. tations and gene conversion events gradually Analyses of these data suggest that gene loss alter internal information; (ii) rearrangements and acquisition are likely to be the primary (e.g., inversions, translocations, plasmid inte­ mechanisms by which bacteria adapt geneti­ gration, and transpositions) alter chromosome cally to novel environments and by which topology with little change in information bacterial populations diverge and form sepa­ content; (iii) deletions cause irreversible loss of rate, evolutionarily distinct species. We sug­ information; and (iv) insertions of foreign ma­ gest that bacterial adaptation and speciation are terial can add novel information to a genome. determined predominantly by acquisition of Although the first two processes can create selectively valuable genes (by horizontal trans­ new genes, they act very slowly. Gene loss and fer) and by loss of weakly contributing genes acquisition are genomic changes that can rad­ (by mutation, deletion, and drift from the ically and rapidly increase fitness or alter some population) during periods of relaxed selec­ aspect of lifestyle. tion. Most thought on genome evolution has fo­ We propose that a limitation of genome cused on how the slow sequence changes can expansion couples the rates of gene acquisition cause divergence of gene functions. This is and loss. Genome size may be limited in part understandable because available data suggest by population-based factors that limit the abil­ that horizontal genetic transfer has been a mi­ ity of cells to selectively maintain information; nor contributor to the evolution of eukaryotic some limitation may also be imposed by phys­ lineages (with notable exceptions, such as the iological considerations. The balance between selective gene acquisition and secondarily im­ posed gene loss implies that addition of a for­ eign gene increases the probability of loss of Jeffrey G. Lawrence, Department of Biological Sciences, Uni­ some resident function of lower selective versity of Pittsburgh, Pittsburgh, PA 15260. John R. Roth, Department of Biology, University of Utah, Salt Lake value. The interaction of these factors, we City, UT 84112. Organization of the Prokaryotic Gmomt, Edited by Robert L. Charlebois, © 1999 American Society for Microbiology, Washington, D.C. 263 264 • LA WRENCE AND ROTH suggest, drives the divergence of bacterial others may provide a benefit only under cer­ types. tain circumstances (e.g., TMAO reductase). In this way, one may sort bacterial genes into DYNAMICS OF GENE LOSS broad classes that reflect their average impor­ tance to the cell (Table 1). Mutations in genes Existence of a Gene Implies making essential or very important contribu­ a Function tions to the cell will be strongly counterse­ Traditional bacterial genetics allows identifi­ lected in bacterial populations, since these cation of gene function by correlating mutant mutants cannot compete effectively against growth phenotypes with biochemical defects. otherwise uncompromised conspecific indi­ One can demonstrate the functional impor­ viduals. However, mutations in genes that do tance of many DNA sequences by observing not contribute to cell fitness (e.g., selfish genes the consequences of their disruption. In con­ on transposons) will not be counterselected, trast, genomic analyses identify genes solely as since these neutral mutants do not put their open reading frames, with possible similarity bearers at a selective disadvantage. to genes of known function but without a di­ Between these extremes lies the gray area rect tie to either phenotype or biochemical of mutations that have subtle effects on fitness; defect. we include two extreme classes of genes. In identifying a gene by its sequence, rather Some genes may make a minimal contribution than by mutations and phenotypes, one as­ to fitness under all growth conditions; others sumes implicitly that the very presence of a may make a large contribution to fitness but gene implies that it must confer a selectable do so only in a rare subset of environments. function. That is, the gene could only have For either class of gene, the average selection remained in the population if the encoded coefficient is low. The fate of mutations in the function is important; that is, mutants lacking most weakly selected genes is governed by a the function show reduced fitness and are re­ complex interaction of natural selection, ran­ moved from the population by natural selec­ dom genetic drift, population size, population tion. This evolutionary argument implies that subdivision, and genetic exchange within the a mutant phenotype (perhaps difficult to dem­ species. onstrate) will result if the gene is disrupted. In For any one species, a different fraction of principle, a few genes might be encountered genes may make up each category in Table 1. which either have just been introduced or In small genomes (e.g., that of Mycoplasmagen­ have escaped selection, and the process of italium), a large fraction of genes are likely to elimination has not yet run its course; data be essential (42), while a smaller fraction of supporting such cases will be pres~nted below. genes are likely to be essential in prokaryotes An important question arises when one tries with larger genomes (e.g., Escherichia colt). Re­ to define the function of a gene (or determine gardless of the distribution, some genes in any whether it is one of the rare nonfunctional genome will fall at the bottom of the list and examples). That is, how important must a make a minimal contribution to cellular fitness function be to assure the maintenance of its (i.e., they are nearly neutral). These genes will gene? How large a fitness contribution must a be at greatest risk for functional loss by mu­ gene confer to remain in a genome? tation, deletion, and genetic drift. This class of genes may comprise a large portion of ge­ A Spectrum of Fitness Contributions nomic information. All bacterial genes are not equally important. In E. coli, few of the 4,286 protein-coding Functions performed by bacterial cells are di­ genes are essential. Isolation of temperature­ verse, and while some are essential for life un­ sensitive lethal mutations suggests that only der all conditions (e.g., RNA polymerase), ~200 genes are essential on rich medium (55). 15. GENOMIC FLUX • 265 TABLE 1 Fitness contributions of bacterial genes Fitness con- Class Physiological role Consequence of null mutation tribution Top Large Essential Lethality High Large Very important Strong impairment Middle Moderate Important Obvious impairment Low (I) Very low Minimally useful in all Subtle impairment; hard to detect experimen­ conditions tally Low (II) Very low Important in rare con- Strong impairment in some environments ditions Neutral None None None This estimate of the minimal number of es­ fitness contributions c2.n be maintained in a sential genes in the E. coli chromosome (even population. If mutation rates are high, a when adjusted for failure to detect some genes stronger selective coefficient would be re­ by this method) is congruent with theoretical quired to maintain a gene in a population of estimates of minimal gene number (256 genes) the same size. Therefore, s is proportional to based on comparisons of several bacterial ge­ the mutation rate, µ,(sex: µ,).As the mutation nomes (42). Moreover, a similar number of rate increases, null mutations in a gene under genes are detected by mutations that cause a weak selection are more likely to drift to fix­ nutritional requirement for growth. Together, ation, since defective alleles are created more these rather important gene classes constitute rapidly than they can be removed by selection. approximately 10% of the E. coli genome; the As population size decreases, loss by drift be­ remaining 90% of genes must make smaller comes more likely and more genes become contributions to fitness or be needed only un­ effectively neutral (49, 50). In these smaller der particular conditions. This conclusion is populations, a larger selective value is required supported by the analysis of E. coli mutants to maintain a gene in the population. That is, described above and by the observation that a gene must make a stronger contribution to the genomes of free-living bacteria vary fitness to be selectively maintained. Therefore, greatly in size. In additism, experimental ap­ s is inversely proportional to the effective pop­ proaches have revealed that lesions in a large ulation size, N, (s ex: µ,/ N,). The dynamics of proportion of genes in the yeast Saccharomyces how selection acts on mutant alleles is influ­ cerevisiae have only minimal effects on fitness enced by the rate of intraspecific recombina­ (65). tion. As the recombination rate increases, se­ lection can more effectively remove the steady A Minimal Fitness Contribution Is accumulation of detrimental alleles from a Required for Gene Maintenance . population, and the species can avoid to some While a complete description of the processes extent the fitness decline mandated by Mul­ governing the selective maintenance
Recommended publications
  • Specificity of Genome Evolution in Experimental Populations Of
    Specificity of genome evolution in experimental PNAS PLUS populations of Escherichia coli evolved at different temperatures Daniel E. Deatheragea,b,c,d, Jamie L. Kepnera,b,c,d, Albert F. Bennette, Richard E. Lenskif,g,1, and Jeffrey E. Barricka,b,c,d,f,1 aCenter for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX 78712; bCenter for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, TX 78712; cInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712; dDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712; eDepartment of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697; fBEACON Center for the Study of Evolution in Action, Michigan State University, East Lansing, MI 48824; and gDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 Edited by Neil H. Shubin, The University of Chicago, Chicago, IL, and approved January 25, 2017 (received for review September 27, 2016) Isolated populations derived from a common ancestor are expected to produce only in environments within a restricted thermal range. diverge genetically and phenotypically as they adapt to different local Adaptation for improved thermotolerance has important impli- environments. To examine this process, 30 populations of Escherichia cations for plant growth (5) and crop productivity (6), especially coli were evolved for 2,000 generations, with six in each of five dif- in light of climate change (7). Directed evolution of microor- ferent thermal regimes: constant 20 °C, 32 °C, 37 °C, 42 °C, and daily ganisms, such as yeast, to function effectively at higher or lower alternations between 32 °C and 42 °C.
    [Show full text]
  • In Vivo Metabolism of [1,6-13C2]Glucose Reveals Distinct
    H OH metabolites OH Article 13 In Vivo Metabolism of [1,6- C2]Glucose Reveals Distinct Neuroenergetic Functionality between Mouse Hippocampus and Hypothalamus Antoine Cherix 1,†, Rajesh Sonti 1,‡, Bernard Lanz 1 and Hongxia Lei 2,3,*,§ 1 Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland; [email protected] (A.C.); [email protected] (R.S.); bernard.lanz@epfl.ch (B.L.) 2 Animal Imaging and Technology (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland 3 Faculty of Medicine, University of Geneva, CH-1206 Geneva, Switzerland * Correspondence: [email protected] † Current address: Wellcome Centre for Integrative Neuroimaging (WIN), Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK. ‡ Current address: Department of Pharmaceutical analysis, National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad- NH 65, Hyderabad 500037, India. § Current address: Wuhan United Imaging Life Science Instruments Ltd., Wuhan 430206, China. Abstract: Glucose is a major energy fuel for the brain, however, less is known about specificities of its metabolism in distinct cerebral areas. Here we examined the regional differences in glucose utilization between the hypothalamus and hippocampus using in vivo indirect 13C magnetic res- 1 13 13 onance spectroscopy ( H-[ C]-MRS) upon infusion of [1,6- C2]glucose. Using a metabolic flux analysis with a 1-compartment mathematical model of brain metabolism, we report that compared to hippocampus, hypothalamus shows higher levels of aerobic glycolysis associated with a marked Citation: Cherix, A.; Sonti, R.; Lanz, gamma-aminobutyric acid-ergic (GABAergic) and astrocytic metabolic dependence.
    [Show full text]
  • Quantitative Analysis of Amino Acid Metabolism in Liver Cancer Links Glutamate Excretion to Nucleotide Synthesis
    Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis Avlant Nilssona,1, Jurgen R. Haanstrab,1, Martin Engqvista, Albert Gerdingc,d, Barbara M. Bakkerb,c, Ursula Klingmüllere, Bas Teusinkb, and Jens Nielsena,f,2 aDepartment of Biology and Biological Engineering, Chalmers University of Technology, SE41296 Gothenburg, Sweden; bSystems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, NL1081HZ Amsterdam, The Netherlands; cLaboratory of Pediatrics, Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, NL-9713AV Groningen, The Netherlands dDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, NL-9713AV Groningen, The Netherlands; eDivision of Systems Biology and Signal Transduction, German Cancer Research Center, D-69120 Heidelberg, Germany; and fNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, DK2800, Denmark Contributed by Jens Nielsen, March 9, 2020 (sent for review November 4, 2019; reviewed by Eytan Ruppin and Matthew G. Vander Heiden) Many cancer cells consume glutamine at high rates; counterintu- the excretion of lactate, glutamate, alanine, and glycine (5). How- itively, they simultaneously excrete glutamate, the first interme- ever, a full genome-wide modeling approach is required to expand diate in glutamine metabolism. Glutamine consumption has been our knowledge of how metabolism functions beyond the canonical linked to replenishment of tricarboxylic acid cycle (TCA) interme- pathways and, in particular, to understand the intricate effects of diates and synthesis of adenosine triphosphate (ATP), but the metabolic compartmentalization and the interplay between ex- reason for glutamate excretion is unclear. Here, we dynamically change fluxes and synthesis of biomass.
    [Show full text]
  • Comparative Genome Evolution Working Group
    Comparative Genome Evolution Working Group COMPARATIVE GENOME EVOLUTION MODIFIED PROPOSAL Introduction Analysis of comparative genomic sequence information from a well-chosen set of organisms is, at present, one of the most effective approaches available to advance biomedical research. The following document describes rationales and plans for selecting targets for genome sequencing that will provide insight into a number of major biological questions that broadly underlie major areas of research funded by the National Institutes of Health, including studies of gene regulation, understanding animal development, and understanding gene and protein function. Genomic sequence data is a fundamental information resource that is required to address important questions about biology: What is the genomic basis for the advent of major morphogenetic or physiological innovations during evolution? How have genomes changed with the addition of new features observed in the eukaryotic lineage, for example the development of an adaptive immune system, an organized nervous system, bilateral symmetry, or multicellularity? What are the genomic correlates or bases for major evolutionary phenomena such as evolutionary rates; speciation; genome reorganization, and origins of variation? Another vital use to which genomic sequence data are applied is the development of more robust information about important non-human model systems used in biomedical research, i.e. how can we identify conserved functional regions in the existing genome sequences of important non- mammalian model systems, so that we can better understand fundamental aspects of, for example, gene regulation, replication, or interactions between genes? NHGRI established a working group to provide the Institute with well-considered scientific thought about the genomic sequences that would most effectively address these questions.
    [Show full text]
  • Nicotinamide Adenine Dinucleotide Is Transported Into Mammalian
    RESEARCH ARTICLE Nicotinamide adenine dinucleotide is transported into mammalian mitochondria Antonio Davila1,2†, Ling Liu3†, Karthikeyani Chellappa1, Philip Redpath4, Eiko Nakamaru-Ogiso5, Lauren M Paolella1, Zhigang Zhang6, Marie E Migaud4,7, Joshua D Rabinowitz3, Joseph A Baur1* 1Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; 2PARC, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; 3Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, United States; 4School of Pharmacy, Queen’s University Belfast, Belfast, United Kingdom; 5Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; 6College of Veterinary Medicine, Northeast Agricultural University, Harbin, China; 7Mitchell Cancer Institute, University of South Alabama, Mobile, United States Abstract Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells *For correspondence: with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties [email protected] results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with †These authors contributed doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate equally to this work that NAD(H) is the imported species.
    [Show full text]
  • Section 4. Guidance Document on Horizontal Gene Transfer Between Bacteria
    306 - PART 2. DOCUMENTS ON MICRO-ORGANISMS Section 4. Guidance document on horizontal gene transfer between bacteria 1. Introduction Horizontal gene transfer (HGT) 1 refers to the stable transfer of genetic material from one organism to another without reproduction. The significance of horizontal gene transfer was first recognised when evidence was found for ‘infectious heredity’ of multiple antibiotic resistance to pathogens (Watanabe, 1963). The assumed importance of HGT has changed several times (Doolittle et al., 2003) but there is general agreement now that HGT is a major, if not the dominant, force in bacterial evolution. Massive gene exchanges in completely sequenced genomes were discovered by deviant composition, anomalous phylogenetic distribution, great similarity of genes from distantly related species, and incongruent phylogenetic trees (Ochman et al., 2000; Koonin et al., 2001; Jain et al., 2002; Doolittle et al., 2003; Kurland et al., 2003; Philippe and Douady, 2003). There is also much evidence now for HGT by mobile genetic elements (MGEs) being an ongoing process that plays a primary role in the ecological adaptation of prokaryotes. Well documented is the example of the dissemination of antibiotic resistance genes by HGT that allowed bacterial populations to rapidly adapt to a strong selective pressure by agronomically and medically used antibiotics (Tschäpe, 1994; Witte, 1998; Mazel and Davies, 1999). MGEs shape bacterial genomes, promote intra-species variability and distribute genes between distantly related bacterial genera. Horizontal gene transfer (HGT) between bacteria is driven by three major processes: transformation (the uptake of free DNA), transduction (gene transfer mediated by bacteriophages) and conjugation (gene transfer by means of plasmids or conjugative and integrated elements).
    [Show full text]
  • Genome Evolution: Mutation Is the Main Driver of Genome Size in Prokaryotes Gabriel A.B
    Genome Evolution: Mutation Is the Main Driver of Genome Size in Prokaryotes Gabriel A.B. Marais, Bérénice Batut, Vincent Daubin To cite this version: Gabriel A.B. Marais, Bérénice Batut, Vincent Daubin. Genome Evolution: Mutation Is the Main Driver of Genome Size in Prokaryotes. Current Biology - CB, Elsevier, 2020, 30 (19), pp.R1083- R1085. 10.1016/j.cub.2020.07.093. hal-03066151 HAL Id: hal-03066151 https://hal.archives-ouvertes.fr/hal-03066151 Submitted on 15 Dec 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. DISPATCH Genome Evolution: Mutation is the Main Driver of Genome Size in Prokaryotes Gabriel A.B. Marais1, Bérénice Batut2, and Vincent Daubin1 1Université Lyon 1, CNRS, Laboratoire de Biométrie et Biologie Évolutive UMR 5558, F- 69622 Villeurbanne, France 2Albert-Ludwigs-University Freiburg, Department of Computer Science, 79110 Freiburg, Germany Summary Despite intense research on genome architecture since the 2000’s, genome-size evolution in prokaryotes has remained puzzling. Using a phylogenetic approach, a new study found that increased mutation rate is associated with gene loss and reduced genome size in prokaryotes. In 2003 [1] and later in 2007 in his book “The Origins of Genome Architecture” [2], Lynch developed his influential theory that a genome’s complexity, represented by its size, is primarily the result of genetic drift.
    [Show full text]
  • Metabolic Flux Analysis—Linking Isotope Labeling and Metabolic Fluxes
    H OH metabolites OH Review Metabolic Flux Analysis—Linking Isotope Labeling and Metabolic Fluxes Yujue Wang 1,2, Fredric E. Wondisford 1, Chi Song 3, Teng Zhang 4 and Xiaoyang Su 1,2,* 1 Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA; [email protected] (Y.W.); [email protected] (F.E.W.) 2 Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA 3 Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH 43210, USA; [email protected] 4 Department of Mathematics, University of Central Florida, Orlando, FL 32816, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-732-235-5447 Received: 14 September 2020; Accepted: 4 November 2020; Published: 6 November 2020 Abstract: Metabolic flux analysis (MFA) is an increasingly important tool to study metabolism quantitatively. Unlike the concentrations of metabolites, the fluxes, which are the rates at which intracellular metabolites interconvert, are not directly measurable. MFA uses stable isotope labeled tracers to reveal information related to the fluxes. The conceptual idea of MFA is that in tracer experiments the isotope labeling patterns of intracellular metabolites are determined by the fluxes, therefore by measuring the labeling patterns we can infer the fluxes in the network. In this review, we will discuss the basic concept of MFA using a simplified upper glycolysis network as an example. We will show how the fluxes are reflected in the isotope labeling patterns. The central idea we wish to deliver is that under metabolic and isotopic steady-state the labeling pattern of a metabolite is the flux-weighted average of the substrates’ labeling patterns.
    [Show full text]
  • Genomes and Their Evolution
    CAMPBELL BIOLOGY IN FOCUS URRY • CAIN • WASSERMAN • MINORSKY • REECE 18 Genomes and Their Evolution Lecture Presentations by Kathleen Fitzpatrick and Nicole Tunbridge, Simon Fraser University © 2016 Pearson Education, Inc. SECOND EDITION Overview: Reading Leaves from the Tree of Life . Complete genome sequences exist for a human, chimpanzee, E. coli, and numerous other prokaryotes, as well as corn, fruit fly, house mouse, orangutan, and others . Comparisons of genomes among organisms provide information about the evolutionary history of genes and taxonomic groups © 2016 Pearson Education, Inc. Genomics is the study of whole sets of genes and their interactions . Bioinformatics is the application of computational methods to the storage and analysis of biological data © 2016 Pearson Education, Inc. Figure 18.1 © 2016 Pearson Education, Inc. Concept 18.1: The Human Genome Project fostered development of faster, less expensive sequencing techniques . The Human Genome Project officially began in 1990, and the sequencing was largely completed by 2003 . Even with automation, the sequencing of all 3 billion base pairs in a haploid set presented a formidable challenge . A major thrust of the Human Genome Project was the development of technology for faster sequencing © 2016 Pearson Education, Inc. The whole-genome shotgun approach was developed by J. Craig Venter and colleagues . This approach starts with cloning and sequencing random DNA fragments . Powerful computer programs are used to assemble the resulting short overlapping sequences into a single continuous sequence © 2016 Pearson Education, Inc. Figure 18.2-s1 Cut the DNA into overlapping fragments short enough for sequencing. Clone the fragments in plasmid or other vectors. © 2016 Pearson Education, Inc.
    [Show full text]
  • Chapter 5 Genome Sequences and Evolution
    © Jones & Bartlett Learning LLC, an Ascend Learning Company. NOT FOR SALE OR DISTRIBUTION. CHAPTER 5 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Genome Sequences © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC and ENOTvolu FOR SALEtion OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION CHAPTER OUTLINE © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 5.1 Introduction 5.13 A Constant Rate of Sequence Divergence Is NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 5.2 Prokaryotic Gene Numbers Range Over an a Molecular Clock Order of Magnitude 5.14 The Rate of Neutral Substitution Can Be 5.3 Total Gene Number Is Known for Several Measured from Divergence of Repeated Eukaryotes Sequences © Jones &5.4 Bartlett How Many Learning, Different LLC Types of Genes Are © Jones5.15 &How Bartlett Did Interrupted Learning, Genes LLC Evolve? NOT FOR SALEThere? OR DISTRIBUTION NOT 5.16FOR Why SALE Are OR Some DISTRIBUTION Genomes So Large? 5.5 The Human Genome Has Fewer Genes Than 5.17 Morphological Complexity Evolves by Originally Expected Adding New Gene Functions 5.6 How
    [Show full text]
  • 1 Quantitative Determinants of Aerobic Glycolysis Identify Flux Through the Enzyme 1 GAPDH As a Limiting Step 2 3 Alexander a Sh
    1 Quantitative determinants of aerobic glycolysis identify flux through the enzyme 2 GAPDH as a limiting step 3 4 Alexander A Shestov1*, Xiaojing Liu1*, Zheng Ser1, Ahmad Cluntun2, Yin P Hung3, Lei 5 Huang4, Dongsung Kim2, Anne Le5, Gary Yellen3, John G Albeck6, Jason W 6 Locasale1,2,4** 7 8 1Division of Nutritional Sciences, Cornell University, Ithaca NY 14850 9 2Field of Biochemistry and Molecular Cell Biology, Department of Molecular Biology 10 and Genetics Cornell University, Ithaca NY 14850 11 3Department of Neurobiology, Harvard Medical School, Boston MA 02115 12 4Field of Computational Biology, Department of Biological Statistics and Computational 13 Biology, Cornell University, Ithaca NY 14850 14 5Department of Pathology and Oncology, Johns Hopkins University School of Medicine, 15 Baltimore, MD 21231 16 6Department of Molecular Cell Biology, University of California Davis, Davis CA 95616 17 * Equal contribution 18 ** Correspondence: [email protected] 19 20 Abstract 21 Aerobic glycolysis or the Warburg Effect (WE) is characterized by the increased 22 metabolism of glucose to lactate. It remains unknown what quantitative changes to the 23 activity of metabolism are necessary and sufficient for this phenotype. We developed a 24 computational model of glycolysis and an integrated analysis using metabolic control 25 analysis (MCA), metabolomics data, and statistical simulations. We identified and 26 confirmed a novel mode of regulation specific to aerobic glycolysis where flux through 27 GAPDH, the enzyme separating lower and upper glycolysis, is the rate-limiting step in 28 the pathway and the levels of fructose (1,6) bisphosphate (FBP), are predictive of the rate 29 and control points in glycolysis.
    [Show full text]
  • On the Law of Directionality of Genome Evolution
    On the Law of Directionality of Genome Evolution Liaofu Luo Laboratory of Theoretical Biophysics, Faculty of Science and Technology, Inner Mongolia University, Hohhot 010021, China *Email address: [email protected] Abstract The problem of the directionality of genome evolution is studied from the information-theoretic view. We propose that the function-coding information quantity of a genome always grows in the course of evolution through sequence duplication, expansion of code, and gene transfer between genomes. The function-coding information quantity of a genome consists of two parts, p-coding information quantity which encodes functional protein and n-coding information quantity which encodes other functional elements except amino acid sequence. The relation of the proposed law to the thermodynamic laws is indicated. The evolutionary trends of DNA sequences revealed by bioinformatics are investigated which afford further evidences on the evolutionary law. It is argued that the directionality of genome evolution comes from species competition adaptive to environment. An expression on the evolutionary rate of genome is proposed that the rate is a function of Darwin temperature (describing species competition) and fitness slope (describing adaptive landscape). Finally, the problem of directly experimental test on the evolutionary directionality is discussed briefly. 1 A law of genomic information The traditional natural sciences mostly focused on matter and energy. Of course, the two are basic categories in the nature. However, parallel to yet different from matter and energy, information constitutes the third fundamental category in natural sciences. One characteristic of a life system is that it contains a large amount of information. Life consists of matter and energy, but it is not just matter and energy.
    [Show full text]