DOCSLIB.ORG

Comparison of Spontaneous and Adaptive Mutation Spectra in Yeast

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparison of Spontaneous and Adaptive Mutation Spectra in Yeast © Indian Academy of Sciences Special section: Stationary-phase mutations in microorganisms Comparison of spontaneous and adaptive mutation spectra in yeast CHRISTOPHER N. GREENE 1 and SUE JINKS-ROBERTSON 1,2,* 1 Graduate Program in Genetics and Molecular Biology, and 2 Department of Biology, Emory University, Atlanta, GA 30322, USA Abstract Adaptive mutations occur in nongrowing populations of cells to overcome strong, nonlethal selection conditions. Several models have been proposed for the molecular mechanism(s) for this phenomenon in Escherichia coli, but the mechanisms involved in adaptive mutagenesis in the yeast Saccharomyces cerevisiae are largely unknown. We present here a comparison of the mutational spectra of spontaneous and adaptive frameshift reversion events in yeast. In contrast to results from E. coli, we find that the mutational spectrum of adaptive mutations in S. cerevisiae is not similar to that seen in mismatch repair defective cells, but rather resembles the spontaneous mutational events that occur during normal growth. [Greene C. N. and Jinks-Robertson S. 1999 Comparisonof spontaneous and adaptive mutation spectra in yeast. J. Genet. 78, 51-55] Introduction Stahl (1988) proposed that the adaptive nature of muta- tional events occurring under starvation conditions could be The classic experiments of Luria and Delbriick (1943) and explained by the inherently biased nature of the bacterial Lederberg and Lederberg (1952) demonstrated that mutations mismatch repair (MMR) system. During the repair of in bacterial cells occur prior to exposure to a selective agent. mismatches generated during DNA synthesis, the MMR Such 'spontaneous' mutations presumably reflect random system specifically targets the newly synthesized strand errors made during DNA synthesis and hence occur without (rather than the strand used as a template for DNA synthesis) regard to their possible utility. Although these experiments for removal and repair, thus preventing the propagation of demonstrated the occurrence of spontaneous mutation events, errors. Stahl proposed that the MMR machinery might work they utihzed a lethal selection scheme that precluded the less efficiently under starvation conditions (alternatively, detection of mutational events that might be occurring after DNA polymerases might be more error prone under starva- exposure to the selective agent. Cairns et al. (1988) first tion conditions), thus allowing time for the cell to assess the documented the accumulation of mutations in nondividing potential usefulness of a mutational intermediate. Mis- bacterial cells in an apparent response to a selective agent. matches thus could be considered transient mutations that These growth-independent mutations were originally termed either are fLxed by DNA replication, or are removed by the 'directed' mutations, a name that reflected a hypothetical MMR machinery. If incorporation of a mutation into the reverse flow of information from protein to gene. Such a transcribed strand of a gene whose function is necessary to reverse flow of information was subsequently discounted restore growth results in the production of a functional gene (Foster and Cairns 1992), and the mutations occurring in product, then growth would ensue and the mutation would nongrowing cells are generally referred to as 'adaptive' be fixed in the genome. If, however, a mutation occurs that mutations. The hallmark of the adaptive-mutation process is does not result in a functional gene product, or occurs in a the accumulation of mutations that specifically restore a gene whose product is irrelevant to growth restoration, then growth phenotype; mutations irrelevant to growth restoration the mutation would be removed by the MMR machinery. do not accumulate (Drake 1991; Foster 1993; Hall 1998). The most intensely studied system for adaptive mutation is reversion of the F'-bome lacI33-lacZ +1 frameshift allele * For correspondence. E-mail: [email protected]. of Escherichia coli in response to lactose exposure (Cairns Keywords. adaptive; mutation; frameshift; yeast. Journal of Genetics, Vol. 78, No. 1, April 1999 51 Christopher IV. Greene and Sue Jinks-Robertson and Foster 1991; Foster 1998). The mechanism for adaptive with the unbiased repair of mismatches that arise in recom- reversion of this allele is qualitatively different from growth- bination intermediates (Petes et al. 1991). To gain further dependent, spontaneous reversion in several respects. First, insight into the molecular mechanism(s) involved in adap- the adaptive frameshift mutations are dependent on bacterial tive mutation in yeast, we have compared the sequence recombination functions whereas spontaneous mutations are spectra of spontaneous (growth-dependent) and adaptive not (Cairns and Foster 1991; Foster 1993; Harris et al. 1994; (growth-independent) frameshift mutations at the LYS2 Foster and Trimarchi 1995a). In addition, adaptive events locus. require the expression of F-factor conjugative functions (Foster and Trimarchi 1995a; Galitski and Roth 1995; Radicella et aL 1995), although the physical act of con- Materials and methods jugation itself is not necessary (Foster and Trimarchi 1995b). Finally, the adaptive reversion spectrum is distinct from that Isolation of Lys + revertants: Strain S JR159 (MATs leu2 ura3 of spontaneous events, and is instead very similar to the trplam ade2 pCYCl-lys2ABgl; see Steele and Jinks- spontaneous reversion spectrum obtained in MMR-deficient Robertson 1992) was grown nonselectively on YPD cells. The adaptive events are almost exclusively one-base- medium (1% yeast extract, 2% Bacto-peptone, 2% dextrose; pair deletions in homopolymer runs, whereas the sponta- 2% agar for plates). Two-day-old colonies were excised neous events are very heterogeneous, consisting of a variety from YPD plates and individually grown overnight in 5 ml of deletions, additions and complex frameshifts (Foster and of liquid YPD. Cells were harvested by centrifugation, Trimarchi 1994; Rosenberg et al. 1994). These data suggest washed with sterile water, and plated on lysine-deficient that a deficiency in the E. coli MMR system may be selective medium (SC-lys medium; see Sherman 1991) at a important in the generation of adaptive mutation events. In density of 108 cells per plate. Lys+ revertants appearing on addition, the major replicative polymerase (DNA polymer- the second day after selective plating were assumed to ase III) has been implicated in the generation of mutations contain spontaneous mutations that occurred during the that accumulate under starvation conditions (Foster et al. nonselective growth period ('early' revertants). Lys + 1995; Harris et al. 1997). Although early work indicated colonies making their initial appearance on days 5-7 after that the only starvation-associated mutations were those that selective plating ('late' revertants) were assumed to contain restored a growth phenotype, more recent studies have adaptive mutations that occurred after selective plating. To demonstrated that additional, nonselected mutations occur ensure independence of all revertants analysed, only a single as well, but at a lower rate (Foster 1997; Torkelson et al. early and a single late revertant were isolated from each 1997). The bacterial data are most consistent with either a independent overnight culture. All revertants were purified 'hypermutational state' model (Boe 1990; Hall 1990), a nonselectively on YPD medium prior to molecular analysis. recombination-based model incorporating F-factor replica- tion (Kuzminov 1995), or a gene amplification model DNA sequence analysis: Cells were grown to saturation in 2 requiring residual function of the allele that needs to be ml YPD medium, and total genomic DNA was prepared by adaptively reverted (Andersson et al. 1998). glass bead lysis (Hoffman and Winston 1987). DNA was In addition to the well-studied bacterial events, adaptive resuspended in a final volume of 100 ktl, and 0.5 pl was used mutations have also been documented in the yeast Saccha- as a template in a 20-ktl PCR reaction. A 900-bp region romyces cerevisiae (Hail 1992; Steele and Jinks-Robertson containing the lys2ABgl reversion window was amplified 1992; Baranowska et al. 1995; Heidenreich and Winters- using primers 5t-GTAACCGGTGACGATGAT-3/ (forward) berger 1997, 1998; Storchova et al. 1998). The molecular and 5'-CCAATTGTCCAGCAGCTC-3t (reverse). Five ~tl of mechanisms involved in adaptive mutagenesis in yeast have the PCR reaction was treated with one unit each of exonu- not been characterized in detail although some genetic data clease I and shrimp alkaline phosphatase to remove the are available. It has been reported that a mutator allele of primers and dNTPs. Standard dideoxynucleotide sequen- DNA polymerase d~ (cdc2-1) increases the rate of both cing was performed directly without further purification spontaneous and adaptive reversion events (Baranowska using 35S-dCTP, Sequenase (USB) and an internal primer et al. 1995) and that elimination of the RAD6 DNA repair (5r-CGCAACAATGGTTACTCT-31). gene has a similar effect (Storchova et aL 1998). These observations suggest the involvement of DNA repair path- ways in the generation of adaptive mutations. In addition, Results and discussion we reported that, although mutations leading to a Lys+ A system for detecting frameshift events phenotype are adaptive and occur only during lysine starva- tion, recombination events producing a Lys+ phenotype The 4.2-kb LYS2 locus contains a single BglII restriction occur under
Load more

Recommended publications
  • Population Size and the Rate of Evolution
    Review Population size and the rate of evolution 1,2 1 3 Robert Lanfear , Hanna Kokko , and Adam Eyre-Walker 1 Ecology Evolution and Genetics, Research School of Biology, Australian National University, Canberra, ACT, Australia 2 National Evolutionary Synthesis Center, Durham, NC, USA 3 School of Life Sciences, University of Sussex, Brighton, UK Does evolution proceed faster in larger or smaller popu- mutations occur and the chance that each mutation lations? The relationship between effective population spreads to fixation. size (Ne) and the rate of evolution has consequences for The purpose of this review is to synthesize theoretical our ability to understand and interpret genomic varia- and empirical knowledge of the relationship between tion, and is central to many aspects of evolution and effective population size (Ne, Box 1) and the substitution ecology. Many factors affect the relationship between Ne rate, which we term the Ne–rate relationship (NeRR). A and the rate of evolution, and recent theoretical and positive NeRR implies faster evolution in larger popula- empirical studies have shown some surprising and tions relative to smaller ones, and a negative NeRR implies sometimes counterintuitive results. Some mechanisms the opposite (Figure 1A,B). Although Ne has long been tend to make the relationship positive, others negative, known to be one of the most important factors determining and they can act simultaneously. The relationship also the substitution rate [5–8], several novel predictions and depends on whether one is interested in the rate of observations have emerged in recent years, causing some neutral, adaptive, or deleterious evolution. Here, we reassessment of earlier theory and highlighting some gaps synthesize theoretical and empirical approaches to un- in our understanding.
    [Show full text]
  • Adaptive Tuning of Mutation Rates Allows Fast Response to Lethal Stress In
    Manuscript 1 Adaptive tuning of mutation rates allows fast response to lethal stress in 2 Escherichia coli 3 4 a a a a a,b 5 Toon Swings , Bram Van den Bergh , Sander Wuyts , Eline Oeyen , Karin Voordeckers , Kevin J. a,b a,c a a,* 6 Verstrepen , Maarten Fauvart , Natalie Verstraeten , Jan Michiels 7 8 a 9 Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Kasteelpark Arenberg 20, 10 3001 Leuven, Belgium b 11 VIB Laboratory for Genetics and Genomics, Vlaams Instituut voor Biotechnologie (VIB) Bioincubator 12 Leuven, Gaston Geenslaan 1, 3001 Leuven, Belgium c 13 Smart Systems and Emerging Technologies Unit, imec, Kapeldreef 75, 3001 Leuven, Belgium * 14 To whom correspondence should be addressed: Jan Michiels, Department of Microbial and 2 15 Molecular Systems (M S), Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, box 16 2460, 3001 Leuven, Belgium, [email protected], Tel: +32 16 32 96 84 1 Manuscript 17 Abstract 18 19 While specific mutations allow organisms to adapt to stressful environments, most changes in an 20 organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often 21 considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in 22 cellular mutation rates as a response to changes in selective pressure. We show that hypermutation 23 independently evolves when different Escherichia coli cultures adapt to high ethanol stress. 24 Furthermore, hypermutator states are transitory and repeatedly alternate with decreases in mutation 25 rate. Specifically, population mutation rates rise when cells experience higher stress and decline again 26 once cells are adapted.
    [Show full text]
  • Adaptive Mutation Sequences Reproduced by Mismatch Repair Deficiency (Escherichia Coli/Muts/Dam/Spontaneous Mutation/Recombination) SIMONNE LONGERICH, ANNE M
    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 12017-12020, December 1995 Biochemistry Adaptive mutation sequences reproduced by mismatch repair deficiency (Escherichia coli/MutS/Dam/spontaneous mutation/recombination) SIMONNE LONGERICH, ANNE M. GALLOWAY, REUBEN S. HARRIS, CINDY WONG, AND SUSAN M. ROSENBERG* Department of Biochemistry, 4-74 Medical Sciences Building, University of Alberta, Edmonton, AB Canada T6G 2H7 Communicated by Allan M. Campbell, Stanford University, Stanford, CA, September 15, 1995 (received for review June 15, 1995) ABSTRACT Adaptive reversions of a lac frameshift mu- mutation (16). The lagging-strand synthesis, which occurs tation in Escherichia coli are -1 deletions in small mononu- along with leading-strand synthesis in vegetative replication, cleotide repeats, whereas growth-dependent reversions are was suggested to produce the heterogeneity of the growth- heterogeneous. The adaptive mutations resemble instability of dependent reversion sequences by, e.g., incorrect joinings of simple repeats, which, in hereditary colon cancer, in yeast, Okazaki fragments (16). Data discourage the view that con- and in E. coli occurs in the absence of mismatch repair. The jugational transfer is a predominant source of adaptive rever- postulate that mismatch repair is disabled transiently during sion (and thus of its unusual sequence spectrum) (17, 18). adaptive mutation in E. coli is supported here by the demon- However, a possible caveat regarding such data has been stration that the growth-dependent mutation spectrum can be suggested (15), and it is also possible that transfer replication made indistinguishable from adaptive mutations by disallow- occurs without actual transfer (16, 18). ing mismatch repair during growth. Physiologically induced (iv) A fourth possibility is that both growth-dependent and mismatch repair deficiency could be an important mutagenic mechanism in in adaptive mutations result from essentially similar polymerase cancers and evolution.
    [Show full text]
  • The Role of Transient Hypermutators in Adaptive Mutation in Escherichia Coli
    Proc. Natl. Acad. Sci. USA Vol. 96, pp. 6862–6867, June 1999 Genetics The role of transient hypermutators in adaptive mutation in Escherichia coli WILLIAM A. ROSCHE† AND PATRICIA L. FOSTER†‡, WITH APPENDIX BY JOHN CAIRNS§ †Department of Environmental Health, Boston University School of Public Health, Boston University School of Medicine, Boston, MA 02118; and §Clinical Trial Service Unit, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom Communicated by Philip Hanawalt, Stanford University, Stanford, CA, April 23, 1999 (received for review January 10, 1999) ABSTRACT Microbial populations under nonlethal se- that bear adaptive mutations than among cells that do not (3). lection can give rise to mutations that relieve the selective In four cases in which this has been tested, the prediction has pressure, a phenomenon that has come to be called ‘‘adaptive been confirmed (3–6). However, it is not possible to determine mutation.’’ One explanation for adaptive mutation is that a from those results what proportion of the mutations that occur small proportion of the cells experience a period of transient during selection arise from hypermutating cells—that will hypermutation, and that these hypermutators account for the depend on the proportion of cells that are in the hypermutable mutations that appear. The experiments reported here inves- state and the degree to which their mutation rate is elevated tigated the contribution that hypermutators make to the (7, 8). Two independent measurements are needed to solve for mutations occurring in a
    [Show full text]
  • Adaptive Reversion of a Frameshift Mutation in Escherichia Coli
    (bpyright 0 199 1 by the Genetics Societyof America Adaptive Reversion of a Frameshift Mutation Escherichiain coli John Cairns*" and Patricia L. Fostert *The Departmentof Cancer Biology, Haruard School of Public Health,Boston, Massachusetts 021 15, and *Department of Environmental Health,Boston University School of Public Health, Boston University School of Medicine, Boston, Massachusetts 021 18 Manuscript received October 9, 1990 Accepted April 23, 1991 ABSTRACT Mutation rates are generally thought not to be influenced by selective forces. This doctrine rests on the results of certain classical studies of the mutations that make bacteria resistant to phages and antibiotics. We have studied a strain of Escherichia coli which constitutively expresses a lad-lacZ fusion containing a frameshift mutation that renders it Lac-. Reversion to Lac+ is a rare event during exponential growth but occurs in stationary cultures when lactose is the only source of energy. No revertants accumulate in the absence of lactose, or in the presence of lactose if there is another, unfulfilled requirement for growth. The mechanism for such mutation in stationary phase is not known, but it requires some function of RecA which is apparently not required for mutation during exponential growth. ECENTexperiments have shown that certain and lexAgreatly reduce the rateof adaptive reversion R spontaneous mutations in Escherichia coli seem under conditions of selection but seem to have no to occur at a higher frequency when they are benefi- effect on the rate of nonadaptive reversion during cial (SHAPIRO1984; CAIRNS,OVERBAUGH and MILLER growth. Thissuggests that the twoclasses of revertant 1988; HALL1988, 1990). Although there have been arise by different mechanisms.
    [Show full text]
  • Transient and Heritable Mutators in Adaptive Evolution in the Lab and in Nature
    Copyright 1998 by the Genetics Society of America Transient and Heritable Mutators in Adaptive Evolution in the Lab and in Nature Susan M. Rosenberg,*,² Carl Thulin* and Reuben S. Harris*,² *Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and ²Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 ABSTRACT Major advances in understanding the molecular mechanism of recombination-dependent stationary- phase mutation in Escherichia coli occurred this past year. These advances are reviewed here, and we also present new evidence that the mutagenic state responsible is transient. We ®nd that most stationary-phase mutants do not possess a heritable stationary-phase mutator phenotype, although a small proportion of heritable mutators was found previously. We outline similarities between this well-studied system and several recent examples of adaptive evolution associated with heritable mutator phenotype in a similarly small proportion of survivors of selection in nature and in the lab. We suggest the following: (1) Transient mutator states may also be a predominant source of adaptive mutations in these latter systems, the heritable mutators being a minority (Rosenberg 1997); (2) heritable mutators may sometimes be a product of, rather than the cause of, hypermutation that gives rise to adaptive mutations. DAPTIVE mutations are those that allow organisms mental system, the stationary-phase mutation was dem- A to succeed in the face of natural or arti®cial selec- onstrated to exist as a process distinct from normal growth- tions. These mutations can arise by any of several routes. dependent mutation by virtue of using a different molecu- ªAdaptive mutationº has also been used to denote a lar mechanism of mutation.
    [Show full text]
  • Generation of Mutation Hotspots in Ageing Bacterial Colonies
    bioRxiv preprint doi: https://doi.org/10.1101/041525; this version posted February 26, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Generation of mutation hotspots in ageing bacterial colonies Agnieszka Sekowska1,3, Sofie Wendel2,3, Morten H. H. Nørholm2* and Antoine Danchin1* 1AMAbiotics SAS, Brain and Spine Institute, Hôpital de la Pitié-Salpêtrière, 47, Boulevard de l'Hôpital, 75013 Paris, France 2Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Alle 6, DK-2970 Hørsholm, Denmark 3These authors contributed equally *For correspondence. E-mail [email protected]; Tel. (+331) 5727 4247; Fax (+331) 5727 4586 or [email protected]. Tel. (+45) 2179 9184 Fax: (+45) 3533 3300 1 bioRxiv preprint doi: https://doi.org/10.1101/041525; this version posted February 26, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract How do ageing bacterial colonies generate adaptive mutants? Over a period of two months, we isolated on ageing colonies outgrowing mutants able to use a new carbon source, and sequenced their genomes. This allowed us to uncover exquisite details on the molecular mechanism behind their adaptation: most mutations were located in just a few hotspots in the genome and over time, mutations increasingly originated from 8-oxo-guanosine, formed exclusively on the transcribed strand. Introduction Bacteria constitute a precious biological model system for studying the molecular details of ageing and evolution.
    [Show full text]
  • Mutation Bias Shapes the Spectrum of Adaptive Substitutions
    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.14.438663; this version posted April 15, 2021. 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 Mutation bias shapes the spectrum of adaptive substitutions 1,2 1,2 3 4,*,@ 1,2,*,@ 2 Alejandro V. Cano , Hana Rozhoňová , Arlin Stoltzfus , David M. McCandlish , and Joshua L. Payne 1 3 Institute of Integrative Biology, ETH, Zurich, Switzerland 2 4 Swiss Institute of Bioinformatics, Lausanne, Switzerland 3 5 Office of Data and Informatics, Material Measurement Laboratory, NIST, and Institute for Bioscience and 6 Biotechnology Research, Rockville, USA 4 7 Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA * 8 These authors contributed equally @ 9 Corresponding author 10 ABSTRACT 11 Evolutionary adaptation often occurs via the fixation of beneficial point mutations, but different types of mutation 12 may differ in their relative frequencies within the collection of substitutions contributing to adaptation in any given 13 species. Recent studies have established that this spectrum of adaptive substitutions is enriched for classes of mutations 14 that occur at higher rates. Yet, little is known at a quantitative level about the precise extent of this enrichment, or 15 its dependence on other factors such as the beneficial mutation supply or demographic conditions. Here we address 16 the extent to which the mutation spectrum shapes the spectrum of adaptive amino acid substitutions by applying a 17 codon-based negative binomial regression model to three large data sets that include thousands of amino acid changes 18 identified in natural and experimental adaptation in S.
    [Show full text]
  • On the Adaptive Disadvantage of Lamarckianism in Rapidly Changing Environments
    On the Adaptive Disadvantage of Lamarckianism in Rapidly Changing Environments Ingo Paenke1,2, Bernhard Sendhoff2, Jon Rowe3, and Chrisantha Fernando3 1 Institute AIFB, University of Karlsruhe, D-76128 Karlsruhe, Germany, E-mail: [email protected] 2 Honda Research Institute Europe GmbH, Carl-Legien-Straße 30, D-63073 Offenbach/Main, Germany, E-mail: [email protected] 3 Systems Biology Centre, University of Birmingham, Birmingham, Edgbaston, B15 2TT, UK, E-mail: [email protected] and [email protected] Abstract. Using a simple simulation model of evolution and learning, this paper provides an evolutionary argument why Lamarckian inheri- tance - the direct transfer of lifetime learning from parent to offspring - may be so rare in nature. Lamarckian inheritance allows quicker ge- netic adaptation to new environmental conditions than non-lamarckian inheritance. While this may be an advantage in the short term, it may be detrimental in the long term, since the population may be less well prepared for future environmental changes than in the absence of Lamar- ckianism. 1 Introduction Natural selection to a first approximation operates with variation that is undi- rected [1]. Lamarck suggested that the results of lifetime learning could be di- rectly passed on to ones offspring [2]. When would we expect directed variation or inheritance of acquired characters to occur? Recent work reveals a range of mechanisms capable of sustaining heritable epigenetic variation [3], pheno- typic memory [4] and neo-Lamarckian inheritance [5], for example: mutational hotspots and adaptive mutations occurring during bacterial stress [6] , chromatin marks that control differentiation in multicellular organisms [7], RNA silencing allowing potential influence by somatic RNA on germ line gene expression [8], inheritance of immune system states by antibody transfer in breast milk [9], and behavioural and symbolic inheritance systems such as food preference, niche con- struction traditions and all information transmission dependent on language [3].
    [Show full text]
  • On Two Quantum Approaches to Adaptive Mutations in Bacteria
    On two quantum approaches to adaptive mutations in bacteria. Vasily Ogryzko* INSERM, CNRS UMR 8126, Universite Paris Sud XI Institut Gustave Roussy, Villejuif, France Key words: Adaptive mutations, quantum mechanics, measurement, decoherence, Lamarck [email protected] http://sites.google.com/site/vasilyogryzko/ ABSTRACT approach. The positive role of environmentally induced decoherence (EID) on both steps of the The phenomenon of adaptive mutations has been adaptation process in the framework of the Q-cell attracting attention of biologists for several approach is emphasized. A starving bacterial cell is decades as challenging the basic premise of the proposed to be in an einselected state. The Central Dogma of Molecular Biology. Two intracellular dynamics in this state has a unitary approaches, based on the quantum theoretical character and is proposed to be interpreted as principles (QMAMs - Quantum Models of ‘exponential growth in imaginary time’, Adaptive Mutations) have been proposed in analogously to the commonly considered order to explain this phenomenon. In the present ‘diffusion’ interpretation of the Schroedinger work, they are termed Q-cell and Q-genome equation. Addition of a substrate leads to Wick approaches and are compared using ‘fluctuation rotation and a switch from ‘imaginary time’ trapping’ mechanism as a general framework. reproduction to a ‘real time’ reproduction regime. Notions of R-error and D-error are introduced, Due to the variations at the genomic level (such as and it is argued that the ‘fluctuation trapping base tautomery), the starving cell has to be model’ can be considered as a QMAM only if it represented as a superposition of different employs a correlation between the R- and D- components, all ‘reproducing in imaginary time’.
    [Show full text]
  • The Structure of Evolutionary Theory: Beyond Neo-Darwinism, Neo
    1 2 3 The structure of evolutionary theory: Beyond Neo-Darwinism, 4 Neo-Lamarckism and biased historical narratives about the 5 Modern Synthesis 6 7 8 9 10 Erik I. Svensson 11 12 Evolutionary Ecology Unit, Department of Biology, Lund University, SE-223 62 Lund, 13 SWEDEN 14 15 Correspondence: [email protected] 16 17 18 19 1 20 Abstract 21 The last decades have seen frequent calls for a more extended evolutionary synthesis (EES) that 22 will supposedly overcome the limitations in the current evolutionary framework with its 23 intellectual roots in the Modern Synthesis (MS). Some radical critics even want to entirely 24 abandon the current evolutionary framework, claiming that the MS (often erroneously labelled 25 “Neo-Darwinism”) is outdated, and will soon be replaced by an entirely new framework, such 26 as the Third Way of Evolution (TWE). Such criticisms are not new, but have repeatedly re- 27 surfaced every decade since the formation of the MS, and were particularly articulated by 28 developmental biologist Conrad Waddington and paleontologist Stephen Jay Gould. 29 Waddington, Gould and later critics argued that the MS was too narrowly focused on genes and 30 natural selection, and that it ignored developmental processes, epigenetics, paleontology and 31 macroevolutionary phenomena. More recent critics partly recycle these old arguments and 32 argue that non-genetic inheritance, niche construction, phenotypic plasticity and developmental 33 bias necessitate major revision of evolutionary theory. Here I discuss these supposed 34 challenges, taking a historical perspective and tracing these arguments back to Waddington and 35 Gould. I dissect the old arguments by Waddington, Gould and more recent critics that the MS 36 was excessively gene centric and became increasingly “hardened” over time and narrowly 37 focused on natural selection.
    [Show full text]
  • Mismatch Repair Protein Mutl Becomes Limiting During Stationary-Phase Mutation
    Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Mismatch repair protein MutL becomes limiting during stationary-phase mutation Reuben S. Harris,1 Gang Feng,2 Kimberly J. Ross,1 Roger Sidhu, Carl Thulin, Simonne Longerich, Susan K. Szigety, Malcolm E. Winkler,2 and Susan M. Rosenberg1,3 Department of Biochemistry, University of Alberta Faculty of Medicine, Edmonton, Alberta T6G 2H7 Canada; 2Department of Microbiology and Molecular Genetics, University of Texas Houston Medical School, Houston, Texas 77030-1501 USA Postsynthesis mismatch repair is an important contributor to mutation avoidance and genomic stability in bacteria, yeast, and humans. Regulation of its activity would allow organisms to regulate their ability to evolve. That mismatch repair might be down-regulated in stationary-phase Escherichia coli was suggested by the sequence spectrum of some stationary-phase (‘‘adaptive’’) mutations and by the observations that MutS and MutH levels decline during stationary phase. We report that overproduction of MutL inhibits mutation in stationary phase but not during growth. MutS overproduction has no such effect, and MutL overproduction does not prevent stationary-phase decline of either MutS or MutH. These results imply that MutS and MutH decline to levels appropriate for the decreased DNA synthesis in stationary phase, whereas functional MutL is limiting for mismatch repair specifically during stationary phase. Modulation of mutation rate and genetic stability in response to environmental or developmental cues, such as stationary phase and stress, could be important in evolution, development, microbial pathogenicity, and the origins of cancer. [Key Words: Mismatch repair; MutL; mutation; adaptive mutation; genetic instability; evolution; stationary phase] Received April 4, 1997; revised version accepted July 18, 1997.
    [Show full text]