DOCSLIB.ORG

Population Size and the Rate of Evolution

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
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. derstanding the relationship and highlight areas that remain poorly understood. Theory: the NeRR of neutral and nearly neutral mutations (s 0) Does population size limit evolution? The neutral substitution rate reflects the mutation rate Do small populations evolve faster or slower than large Neutral and effectively neutral mutations have fitness populations? When and why does population size limit effects at or very close to zero (s 0, Nejsj<<1, Box 2); adaptation? Answering these questions is important for therefore, their fate is dominated by genetic drift and understanding present-day diversity and the evolutionary largely unaffected by selection. Genetic drift is the stochas- past and future of life on Earth [1–3]. A quantitative tic fluctuation in allele frequencies caused by random answer requires one to measure the ‘rate of evolution’, differences in the fecundity and survival of individuals. and link it to population size. As Ne increases, genetic drift becomes weaker because the Although there are many ways to measure the rate of larger the population, the smaller the proportional impact evolution, in this review we specifically focus on the rela- of each random event that concerns just one individual. tionship between effective population size and the rate of Theory predicts that the increased production of neutral molecular evolution, defined as the rate at which new and effectively neutral mutations in larger populations is substitutions accumulate in the genome over time. Substi- exactly balanced by the decreased probability that each tution rates can be measured from DNA sequence data for mutation will fix through genetic drift ([9]; Box 3 provides a almost any lineage [4]. They provide a convenient way to mathematical description, and describes how census and understand the relationship between effective population effective population size combine to determine rates of size and the rate of evolution, and additional data can be evolution). As a result, the neutral substitution rate equals used to distinguish between rates of adaptive, deleterious, the mutation rate, no matter what the value of Ne. Thus, if and neutral evolution. A substitution occurs when a new the mutation rate does not change, then the NeRR for mutation spreads to fixation in a population; so the sub- neutral mutations will be flat (as shown in Figure 1A,B, stitution rate depends on both the rate at which new lines for s = 0). The observation that the neutral substitution rate equals the mutation rate is surprisingly robust, despite Corresponding author: Lanfear, R. ([email protected]). Keywords: population size; molecular evolution; mutation rate; substitution rate; the simplicity of the initial theory from which it was genetic drift; natural selection. derived (Box 3). For example, factors such as interference 0169-5347/$ – see front matter among mutations [which can have important effects on the ß 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.tree.2013.09.009 NeRR for mutations under selection (i.e., with s 6¼ 0), see below] do not affect the rate of neutral substitution [10,11], and so will not change the NeRR for neutral and effectively neutral mutations. A recent study suggested that the Trends in Ecology & Evolution, January 2014, Vol. 29, No. 1 33 Review Trends in Ecology & Evolution January 2014, Vol. 29, No. 1 Box 1. Estimating effective population size The effective population size (Ne) provides a measure of the power of in large part because there are so few estimates of Ne available. genetic drift, such that increasing Ne is associated with decreasing rates Surprisingly estimates of Ne from the variation in allele frequencies of genetic drift [81,83]. In an ‘ideal’ population – defined as one in which and neutral DNA sequence diversity disagree, although they have population size is constant, and in which offsprings’ genes are randomly rarely been applied to the same taxa [86]. The reasons for this sampled from the parental generation – Ne will be equal to the census discrepancy are unknown. population size, NC [83]. However, Ne is usually a lot lower than NC Because mutations of different selective effects spend different because natural populations have many characteristics that reduce Ne amounts of time in a population, it is important for studies of the [84]. Different parts of the genome can also differ in Ne (Box 4). NeRR to pay close attention to the timescale over which Ne should be Broadly speaking, there are four methods that can be used to calculated. If Ne is constant over time and there is no linkage, then all estimate Ne: (i) the reduction in Ne relative to NC can be estimated mutations will experience the same Ne and any accurate estimate of from the species life history; (ii) Ne can be estimated from the variance Ne will be appropriate for any type of mutation. However, if Ne in allele frequencies between generations; (iii) Ne can be estimated changes over time or there is linkage, then different mutations will from genetic polymorphism data; and (iv) Ne can be estimated from experience different Ne because strongly selected mutations are its correlates, such as body size [67–71,81,84,85]. The last of these either fixed or lost much more rapidly than neutral mutations [33]. methods has been used in the vast majority of empirical studies This can lead to a mismatch between the Ne that can be estimated because estimating Ne using the other methods requires substantially and the Ne of interest. This kind of mismatch might, for example, more information. However, no systematic analysis has been explain why two Drosophila species with different estimates of Ne conducted into whether factors such as body size correlate with Ne, appear to have similar rates of adaptive evolution [22]. neutral substitution rate is not equal to the mutation rate Accounting for variation in mutation rates in situations where there are overlapping generations and Of course, we rarely expect the mutation rate per individ- fluctuating population size [12]. However, it seems likely ual per year to be equal in different populations or species, that the reported effect is in fact due to changes in the which means that empirical estimates of the NeRR for mutation rate induced by changes in the generation time neutral mutations may not be flat. For example, mammals when populations expand or contract, rather than a true with larger Ne also tend to have higher mutation rates per difference between the neutral substitution rate and the year because they tend to have shorter generation times mutation rate. [13], creating a positive NeRR for neutral mutations. (A) (C) 4×10−8 20 s (×10−4) 10 5 1 0 2×10−8 10 Substuon rate 0.00 Substuon rate / mutaon 0 0 5000 10000 1×10−4 1×10−2 1×100 Effecve populaon size (Ne) Nes (B) (D) 1×10−9 1.00 s (×10−4) 0 −1 5×10−10 −5 0.50 −10 Substuon rate 0.00 Substuon rate / mutaon 0.00 0 5000 10000 1×10−4 1×10−2 1×100 Effecve populaon size (Ne) Nes TRENDS in Ecology & Evolution Figure 1. The relationship between substitution rate (in substitutions per site per year) and effective population size (Ne) under genetic drift and natural selection (the NeRR) À9 [8]. These relationships were calculated assuming a mutation rate of 1 Â 10 mutations per site per year, approximately that found in humans. (A,B) show the substitution rate of mutations for a range of positive (A) and negative (B) selection coefficients (denoted ‘s’). (C,D) show the same data, but in this case the y-axis shows the substitution rate relative to the mutation rate, and the x-axis shows the product of Ne and the selection coefficient for positive (C) and negative (D) mutations respectively. A dashed line highlights where Nes = 1, below which mutations are often considered ‘effectively neutral’. Note that genetic drift predicts a flat NeRR for neutral mutations, where s = 0.00 in (A,B). In (C,D), this is reflected by the substitution rate equaling the mutation rate, giving a value of 1 on the y-axis, when Nes = 0.
Load more

Recommended publications
  • Joint Effects of Genetic Hitchhiking and Background Selection on Neutral Variation
    Copyright 2000 by the Genetics Society of America Joint Effects of Genetic Hitchhiking and Background Selection on Neutral Variation Yuseob Kim and Wolfgang Stephan Department of Biology, University of Rochester, Rochester, New York 14627 Manuscript received December 7, 1999 Accepted for publication March 20, 2000 ABSTRACT Due to relatively high rates of strongly selected deleterious mutations, directional selection on favorable alleles (causing hitchhiking effects on linked neutral polymorphisms) is expected to occur while a deleteri- ous mutation-selection balance is present in a population. We analyze this interaction of directional selection and background selection and study their combined effects on neutral variation, using a three- locus model in which each locus is subjected to either deleterious, favorable, or neutral mutations. Average heterozygosity is measured by simulations (1) at the stationary state under the assumption of recurrent hitchhiking events and (2) as a transient level after a single hitchhiking event. The simulation results are compared to theoretical predictions. It is shown that known analytical solutions describing the hitchhiking effect without background selection can be modi®ed such that they accurately predict the joint effects of hitchhiking and background on linked, neutral variation. Generalization of these results to a more appro- priate multilocus model (such that background selection can occur at multiple sites) suggests that, in regions of very low recombination rates, stationary levels of nucleotide diversity are primarily determined by hitchhiking, whereas in regions of high recombination, background selection is the dominant force. The implications of these results on the identi®cation and estimation of the relevant parameters of the model are discussed.
    [Show full text]
  • Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B
    Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B. M ü ller, G ü nter P. Wagner, and Werner Callebaut, editors The Evolution of Cognition , edited by Cecilia Heyes and Ludwig Huber, 2000 Origination of Organismal Form: Beyond the Gene in Development and Evolutionary Biology , edited by Gerd B. M ü ller and Stuart A. Newman, 2003 Environment, Development, and Evolution: Toward a Synthesis , edited by Brian K. Hall, Roy D. Pearson, and Gerd B. M ü ller, 2004 Evolution of Communication Systems: A Comparative Approach , edited by D. Kimbrough Oller and Ulrike Griebel, 2004 Modularity: Understanding the Development and Evolution of Natural Complex Systems , edited by Werner Callebaut and Diego Rasskin-Gutman, 2005 Compositional Evolution: The Impact of Sex, Symbiosis, and Modularity on the Gradualist Framework of Evolution , by Richard A. Watson, 2006 Biological Emergences: Evolution by Natural Experiment , by Robert G. B. Reid, 2007 Modeling Biology: Structure, Behaviors, Evolution , edited by Manfred D. Laubichler and Gerd B. M ü ller, 2007 Evolution of Communicative Flexibility: Complexity, Creativity, and Adaptability in Human and Animal Communication , edited by Kimbrough D. Oller and Ulrike Griebel, 2008 Functions in Biological and Artifi cial Worlds: Comparative Philosophical Perspectives , edited by Ulrich Krohs and Peter Kroes, 2009 Cognitive Biology: Evolutionary and Developmental Perspectives on Mind, Brain, and Behavior , edited by Luca Tommasi, Mary A. Peterson, and Lynn Nadel, 2009 Innovation in Cultural Systems: Contributions from Evolutionary Anthropology , edited by Michael J. O ’ Brien and Stephen J. Shennan, 2010 The Major Transitions in Evolution Revisited , edited by Brett Calcott and Kim Sterelny, 2011 Transformations of Lamarckism: From Subtle Fluids to Molecular Biology , edited by Snait B.
    [Show full text]
  • An Unusually Low Microsatellite Mutation Rate in Dictyostelium Discoideum,An Organism with Unusually Abundant Microsatellites
    Copyright Ó 2007 by the Genetics Society of America DOI: 10.1534/genetics.107.076067 An Unusually Low Microsatellite Mutation Rate in Dictyostelium discoideum,an Organism With Unusually Abundant Microsatellites Ryan McConnell, Sara Middlemist, Clea Scala, Joan E. Strassmann and David C. Queller1 Department of Ecology and Evolutionary Biology, Rice University, Houston, Texas 77005 Manuscript received May 18, 2007 Accepted for publication September 4, 2007 ABSTRACT The genome of the social amoeba Dictyostelium discoideum is known to have a very high density of microsatellite repeats, including thousands of triplet microsatellite repeats in coding regions that apparently code for long runs of single amino acids. We used a mutation accumulation study to see if unusually high microsatellite mutation rates contribute to this pattern. There was a modest bias toward mutations that increase repeat number, but because upward mutations were smaller than downward ones, this did not lead to a net average increase in size. Longer microsatellites had higher mutation rates than shorter ones, but did not show greater directional bias. The most striking finding is that the overall mutation rate is the lowest reported for microsatellites: 1 3 10À6 for 10 dinucleotide loci and 6 3 10À6 for 52 trinucleotide loci (which were longer). High microsatellite mutation rates therefore do not explain the high incidence of microsatellites. The causal relation may in fact be reversed, with low mutation rates evolving to protect against deleterious fitness effects of mutation at the numerous microsatellites. ICROSATELLITES, also known as simple se- In humans, certain triplet repeats that occur in or M quence repeats, are long stretches of a short near coding regions are subject to expansions that (1–6 bp), tandemly repeated DNA unit, such as the directly cause genetic diseases (Ashley and Warren motif CAA repeated 20 times.
    [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]
  • IN EVOLUTION JACK LESTER KING UNIVERSITY of CALIFORNIA, SANTA BARBARA This Paper Is Dedicated to Retiring University of California Professors Curt Stern and Everett R
    THE ROLE OF MUTATION IN EVOLUTION JACK LESTER KING UNIVERSITY OF CALIFORNIA, SANTA BARBARA This paper is dedicated to retiring University of California Professors Curt Stern and Everett R. Dempster. 1. Introduction Eleven decades of thought and work by Darwinian and neo-Darwinian scientists have produced a sophisticated and detailed structure of evolutionary ,theory and observations. In recent years, new techniques in molecular biology have led to new observations that appear to challenge some of the basic theorems of classical evolutionary theory, precipitating the current crisis in evolutionary thought. Building on morphological and paleontological observations, genetic experimentation, logical arguments, and upon mathematical models requiring simplifying assumptions, neo-Darwinian theorists have been able to make some remarkable predictions, some of which, unfortunately, have proven to be inaccurate. Well-known examples are the prediction that most genes in natural populations must be monomorphic [34], and the calculation that a species could evolve at a maximum rate of the order of one allele substitution per 300 genera- tions [13]. It is now known that a large proportion of gene loci are polymorphic in most species [28], and that evolutionary genetic substitutions occur in the human line, for instance, at a rate of about 50 nucleotide changes per generation [20], [24], [25], [26]. The puzzling observation [21], [40], [46], that homologous proteins in different species evolve at nearly constant rates is very difficult to account for with classical evolutionary theory, and at the very least gives a solid indication that there are qualitative differences between the ways molecules evolve and the ways morphological structures evolve.
    [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]
  • Estimating Effective Population Size Or Mutation Rate Using the Frequencies of Mutations of Various Classes in a Sample of DNA Sequences
    Copyright 0 1994 by the Genetics Society of America Estimating Effective Population Size or Mutation Rate Using the Frequencies of Mutations of Various Classes in a Sample of DNA Sequences Yun-xin FU Center for Demographic and Population Genetics, University of Texas, Houston, Texas 77225 Manuscript received February 18, 1994 Accepted for publication August 27, 1994 ABSTRACT Mutations resulting in segregating sites of a sample of DNA sequences can be classified by size and type and the frequencies of mutations of different sizes and types can be inferred from the sample. A framework for estimating the essential parameter 8 = 4Nu utilizing the frequencies of mutations of various sizes and types is developed in this paper, where N is the effective size of a population and p is mutation rate per sequence per generation.The framework is a combination of coalescent theory, general linear model and Monte-Carlo integration, which leads to two new estimators 6, and 6, as well as a general Watterson’s estimator 6, and a general Tajima’s estimator 6,. The greatest strength of the framework is that it can be used under a variety of population models. The properties of the framework and the four estimators bK, e,,, 6, and 6, are investigated under three important population models: the neutral Wright-Fisher model, the neutral model with recombination and the neutral Wright’s finite-islands model. Under all these models, it is shown that 6, is the best estimator among the four even when recombination rate or migration rate has to be estimated. Under the neutral Wright-Fisher model, it is shown that the new estimator 6,has avariance close to alower bound ofvariances of allunbiased estimators of Owhichsuggests that 6, is a:ery efficient estimator.
    [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]
  • Detecting the Form of Selection from DNA Sequence Data
    Outlook COMMENT Male:female mutation ratio muscular dystrophy, neurofibromatosis and retinoblast- outcome of further investigation, this unique transposition oma), there is a large male excess. So, I believe the evidence event and perhaps others like it are sure to provide impor- is convincing that the male base-substitution rate greatly tant cytogenetic and evolutionary insights. exceeds the female rate. There are a number of reasons why the historical Acknowledgements male:female mutation ratio is likely to be less than the I have profited greatly from discussions with my colleagues current one, the most important being the lower age of B. Dove, B. Engels, C. Denniston and M. Susman. My reproduction in the earliest humans and their ape-like greatest debt is to D. Page for a continuing and very fruitful ancestors. More studies are needed. But whatever the dialog and for providing me with unpublished data. References Nature 406, 622–625 6 Engels, W.R. et al. (1994) Long-range cis preference in DNA 1 Vogel, F. and Motulsky, A. G. (1997) Human Genetics: 4 Shimmin, L.C. et al. (1993) Potential problems in estimating homology search over the length of a Drosophila chromosome. Problems and Approaches. Springer-Verlag the male-to-female mutation rate ratio from DNA sequence Science 263, 1623–1625 2 Crow, J. F. (1997) The high spontaneous mutation rate: is it a data. J. Mol. Evol. 37, 160–166 7 Crow, J.F. (2000) The origins, patterns and implications of health risk? Proc. Natl. Acad. Sci. U. S. A. 94, 8380–8386 5 Richardson, C. et al.
    [Show full text]