Accumulation of Deleterious Mutations During Bacterial Range Expansions

Recent theoretical work suggested that deleterious mutations could accumulate during the range expansion of a species, negatively affecting its fitness. Recent theory predicts that the fitness of pioneer populations can decline when species expand their range, due to high rates of genetic drift on wave fronts making selection less efficient at purging deleterious variants. To test these predictions, we studied the fate of mutator bacteria expanding their range for 1650 generations on agar plates. In agreement with theory, we find that growth abilities of strains with a high mutation rate (HMR lines) decreased significantly over time, unlike strains with a lower mutation rate (LMR lines) that present three to four times fewer mutations. Estimation of the distribution of fitness effect under a spatially explicit model reveals a mean negative effect for new mutations (−0.38%), but it suggests that both advantageous and deleterious mutations have accumulated during the experiment. Furthermore, the fitness of HMR lines measured in different environments has decreased relative to the ancestor strain, whereas that of LMR lines remained unchanged. Contrastingly, strains with a HMR evolving in a well-mixed environment accumulated less mutations than agar-evolved strains and showed an increased fitness relative to the ancestor. Our results suggest that spatially expanding species are affected by deleterious mutations, leading to a drastic impairment of their evolutionary potential.

[1]  Hassan Sakhtah,et al.  Convergent evolution of hyperswarming leads to impaired biofilm formation in pathogenic bacteria. , 2013, Cell reports.

[2]  J. Miller,et al.  Predicting the Functional Effect of Amino Acid Substitutions and Indels , 2012, PloS one.

[3]  D. Fusco,et al.  Watching Populations Melt Down. , 2016, Biophysical journal.

[4]  Richard E. Lenski,et al.  Tempo and mode of genome evolution in a 50,000-generation experiment , 2016, Nature.

[5]  K. Foster,et al.  A Quantitative Test of Population Genetics Using Spatiogenetic Patterns in Bacterial Colonies , 2011, The American Naturalist.

[6]  Robert H. Austin,et al.  An analogy between the evolution of drug resistance in bacterial communities and malignant tissues , 2011, Nature Reviews Cancer.

[7]  C. Tyler-Smith,et al.  Deleterious- and disease-allele prevalence in healthy individuals: insights from current predictions, mutation databases, and population-scale resequencing. , 2012, American journal of human genetics.

[8]  Jeffrey E. Barrick,et al.  Genome dynamics during experimental evolution , 2013, Nature Reviews Genetics.

[9]  M. Lynch,et al.  The mutational meltdown in asexual populations. , 1993, The Journal of heredity.

[10]  P. Keightley,et al.  Interference among deleterious mutations favours sex and recombination in finite populations , 2006, Nature.

[11]  Chang-Xing Ma,et al.  Fluctuation AnaLysis CalculatOR: a web tool for the determination of mutation rate using Luria-Delbrück fluctuation analysis , 2009, Bioinform..

[12]  J. Chrast,et al.  Low rate of somatic mutations in a long-lived oak tree , 2017, bioRxiv.

[13]  B. Charlesworth,et al.  Some evolutionary consequences of deleterious mutations , 2004, Genetica.

[14]  Claus O. Wilke,et al.  The Speed of Adaptation in Large Asexual Populations , 2004, Genetics.

[15]  A. Clark,et al.  Estimating the mutation load in human genomes , 2015, Nature Reviews Genetics.

[16]  D. Nelson,et al.  Genetic drift at expanding frontiers promotes gene segregation , 2007, Proceedings of the National Academy of Sciences.

[17]  J. Chrast,et al.  Low number of fixed somatic mutations in a long-lived oak tree , 2017, Nature Plants.

[18]  B. Charlesworth,et al.  The pattern of neutral molecular variation under the background selection model. , 1995, Genetics.

[19]  M. Lynch Evolution of the mutation rate. , 2010, Trends in genetics : TIG.

[20]  J. Haigh The accumulation of deleterious genes in a population--Muller's Ratchet. , 1978, Theoretical population biology.

[21]  J. Shendure,et al.  The origins, determinants, and consequences of human mutations , 2015, Science.

[22]  Laurent Excoffier,et al.  Distance from sub-Saharan Africa predicts mutational load in diverse human genomes , 2015, Proceedings of the National Academy of Sciences.

[23]  Klaus Peter Schliep,et al.  phangorn: phylogenetic analysis in R , 2010, Bioinform..

[24]  T. Lenormand,et al.  A GENERAL MULTIVARIATE EXTENSION OF FISHER'S GEOMETRICAL MODEL AND THE DISTRIBUTION OF MUTATION FITNESS EFFECTS ACROSS SPECIES , 2006, Evolution; international journal of organic evolution.

[25]  G. Beslon,et al.  New insights into bacterial adaptation through in vivo and in silico experimental evolution , 2012, Nature Reviews Microbiology.

[26]  M. DePristo,et al.  The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. , 2010, Genome research.

[27]  P. Foster,et al.  Methods for determining spontaneous mutation rates. , 2006, Methods in enzymology.

[28]  Timothy B Sackton,et al.  Natural Selection Constrains Neutral Diversity across A Wide Range of Species , 2014, bioRxiv.

[29]  R. A. Fisher,et al.  The Genetical Theory of Natural Selection , 1931 .

[30]  M. Whitlock,et al.  Mutation Load: The Fitness of Individuals in Populations Where Deleterious Alleles Are Abundant , 2012 .

[31]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[32]  B. Maier,et al.  Differential interaction forces govern bacterial sorting in early biofilms , 2015, eLife.

[33]  M. Kirkpatrick,et al.  Expansion Load and the Evolutionary Dynamics of a Species Range , 2015, The American Naturalist.

[34]  K. Korolev,et al.  Genetic demixing and evolution in linear stepping stone models. , 2010, Reviews of modern physics.

[35]  F. Taddei,et al.  Highly variable mutation rates in commensal and pathogenic Escherichia coli. , 1997, Science.

[36]  A. F. Bennett,et al.  The Molecular Diversity of Adaptive Convergence , 2012, Science.

[37]  J. Pritchard,et al.  The deleterious mutation load is insensitive to recent population history , 2013, Nature Genetics.

[38]  I. Gordo,et al.  Sex and Deleterious Mutations , 2008, Genetics.

[39]  R. Kassen,et al.  The properties of spontaneous mutations in the opportunistic pathogen Pseudomonas aeruginosa , 2016, BMC Genomics.

[40]  Daniel B. Weissman,et al.  The Rate of Adaptation in Large Sexual Populations with Linear Chromosomes , 2013, Genetics.

[41]  Jeffrey E. Barrick,et al.  Genome evolution and adaptation in a long-term experiment with Escherichia coli , 2009, Nature.

[42]  C. Geyer,et al.  A COMPREHENSIVE MODEL OF MUTATIONS AFFECTING FITNESS AND INFERENCES FOR ARABIDOPSIS THALIANA , 2002, Evolution; international journal of organic evolution.

[43]  D. Reich,et al.  No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans , 2014, Nature Genetics.

[44]  S. Sørensen,et al.  Facultative Control of Matrix Production Optimizes Competitive Fitness in Pseudomonas aeruginosa PA14 Biofilm Models , 2015, Applied and Environmental Microbiology.

[45]  A. Murray,et al.  Spatially Constrained Growth Enhances Conversional Meltdown. , 2016, Biophysical journal.

[46]  M. Kirkpatrick,et al.  On the accumulation of deleterious mutations during range expansions. , 2013, Molecular ecology.

[47]  Hervé Le Nagard,et al.  Mutators and sex in bacteria: conflict between adaptive strategies. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[48]  D. J. Kiviet,et al.  Stochasticity of metabolism and growth at the single-cell level , 2014, Nature.

[49]  I. Gordo,et al.  Rate and effects of spontaneous mutations that affect fitness in mutator Escherichia coli , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[50]  Melanie J. I. Müller,et al.  Selective sweeps in growing microbial colonies. , 2012, Physical biology.

[51]  Kirk E Lohmueller,et al.  The distribution of deleterious genetic variation in human populations. , 2014, Current opinion in genetics & development.

[52]  A. M. Lisewski,et al.  Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks , 2012, Science.

[53]  Michael M. Desai,et al.  Clonal Interference, Multiple Mutations and Adaptation in Large Asexual Populations , 2008, Genetics.

[54]  Wei Yang,et al.  Structure and function of mismatch repair proteins. , 2000, Mutation research.

[55]  G. Sella,et al.  The impact of recent population history on the deleterious mutation load in humans and close evolutionary relatives , 2016 .

[56]  L. Excoffier,et al.  Genetic surfing in human populations: from genes to genomes , 2016, bioRxiv.

[57]  L. Excoffier,et al.  Impact of range expansions on current human genomic diversity. , 2014, Current opinion in genetics & development.

[58]  Arthur W. Covert,et al.  Experiments on the role of deleterious mutations as stepping stones in adaptive evolution , 2013, Proceedings of the National Academy of Sciences.

[59]  Ryan D. Hernandez,et al.  Proportionally more deleterious genetic variation in European than in African populations , 2008, Nature.

[60]  I. Matic,et al.  Evolution of mutation rates in bacteria , 2006, Molecular microbiology.

[61]  B. Waclaw,et al.  Allele surfing promotes microbial adaptation from standing variation. , 2016, Ecology letters.

[62]  R. Schaaper,et al.  The role of the mutT gene of Escherichia coli in maintaining replication fidelity. , 1997, FEMS microbiology reviews.

[63]  S. Ichihara,et al.  Decreasing accumulation of acetate in a rich medium by Escherichia coli on introduction of genes on a multicopy plasmid. , 1995, Bioscience, biotechnology, and biochemistry.

[64]  Jacob A. Tennessen,et al.  Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes , 2012, Science.

[65]  Haixu Tang,et al.  Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing , 2012, Proceedings of the National Academy of Sciences.

[66]  Annik Nanchen,et al.  Nonlinear Dependency of Intracellular Fluxes on Growth Rate in Miniaturized Continuous Cultures of Escherichia coli , 2006, Applied and Environmental Microbiology.

[67]  Yongwook Choi,et al.  PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels , 2015, Bioinform..

[68]  Björn Usadel,et al.  Trimmomatic: a flexible trimmer for Illumina sequence data , 2014, Bioinform..

[69]  Benjamin H. Good,et al.  Distribution of fixed beneficial mutations and the rate of adaptation in asexual populations , 2012, Proceedings of the National Academy of Sciences.

[70]  Pablo Cingolani,et al.  © 2012 Landes Bioscience. Do not distribute. , 2022 .

[71]  M. Bamshad,et al.  Characteristics of neutral and deleterious protein-coding variation among individuals and populations. , 2014, American journal of human genetics.

[72]  Haixu Tang,et al.  On the Mutational Topology of the Bacterial Genome , 2013, G3: Genes, Genomes, Genetics.

[73]  J. Felsenstein Evolutionary trees from DNA sequences: A maximum likelihood approach , 2005, Journal of Molecular Evolution.

[74]  Joaquin Dopazo,et al.  The role of the interactome in the maintenance of deleterious variability in human populations , 2014, Molecular systems biology.

[75]  Michael Doebeli,et al.  EXPERIMENTAL EVIDENCE FOR SYMPATRIC ECOLOGICAL DIVERSIFICATION DUE TO FREQUENCY‐DEPENDENT COMPETITION IN ESCHERICHIA COLI , 2004, Evolution; international journal of organic evolution.

[76]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[77]  Oskar Hallatschek,et al.  LIFE AT THE FRONT OF AN EXPANDING POPULATION , 2008, Evolution; international journal of organic evolution.

[78]  Luca Peliti,et al.  The Rate of Beneficial Mutations Surfing on the Wave of a Range Expansion , 2011, PLoS Comput. Biol..

[79]  F. THE MUTATION LOAD IN SMALL POPULATIONS , 2022 .

[80]  H. A. Orr,et al.  The rate of adaptation in asexuals. , 2000, Genetics.

[81]  R. Punnett,et al.  The Genetical Theory of Natural Selection , 1930, Nature.

[82]  Thomas G. Doak,et al.  Drift-barrier hypothesis and mutation-rate evolution , 2012, Proceedings of the National Academy of Sciences.

[83]  Laurent Excoffier,et al.  Expansion load: recessive mutations and the role of standing genetic variation , 2014, bioRxiv.

[84]  J. Pannell,et al.  Range Expansion Compromises Adaptive Evolution in an Outcrossing Plant , 2017, Current Biology.

[85]  H. Stefánsson,et al.  Identification of a large set of rare complete human knockouts , 2015, Nature Genetics.