Skip to main content
SpringerLink
Log in

Mutation Exposed: A Neutral Explanation for Extreme Base Composition of an Endosymbiont Genome

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

The influence of neutral mutation pressure versus selection on base composition evolution is a subject of considerable controversy. Yet the present study represents the first explicit population genetic analysis of this issue in prokaryotes, the group in which base composition variation is most dramatic. Here, we explore the impact of mutation and selection on the dynamics of synonymous changes in Buchnera aphidicola, the AT-rich bacterial endosymbiont of aphids. Specifically, we evaluated three forms of evidence. (i) We compared the frequencies of directional base changes (AT→GC vs. GC→AT) at synonymous sites within and between Buchnera species, to test for selective preference versus effective neutrality of these mutational categories. Reconstructed mutational changes across a robust intraspecific phylogeny showed a nearly 1:1 AT→GC:GC→AT ratio. Likewise, stationarity of base composition among Buchnera species indicated equal rates of AT→GC and GC→AT substitutions. The similarity of these patterns within and between species supported the neutral model. (ii) We observed an equivalence of relative per-site AT mutation rate and current AT content at synonymous sites, indicating that base composition is at mutational equilibrium. (iii) We demonstrated statistically greater equality in the frequency of mutational categories in Buchnera than in parallel mammalian studies that documented selection on synonymous sites. Our results indicate that effectively neutral mutational pressure, rather than selection, represents the major force driving base composition evolution in Buchnera. Thus they further corroborate recent evidence for the critical role of reduced N e in the molecular evolution of bacterial endosymbionts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • P Abbot NA Moran (2002) ArticleTitleExtremely low levels of genetic polymorphism in endosymbionts (Buchnera) of aphids (Pemphigus) Mol Ecol 11 2649–2660

    Google Scholar 

  • H Akashi (1995) ArticleTitleInferring weak selection from patterns of polymorphism and divergence at “silent” sites in Drosophila DNA Genetics 139 1067–1076 Occurrence Handle1:CAS:528:DyaK28XhsFWgtL0%3D Occurrence Handle7713409

    CAS  PubMed  Google Scholar 

  • H Akashi (1996) ArticleTitleMolecular evolution between Drosophila melanogaster and D simulans: Reduced codon bias faster rates of amino acid substitution and larger proteins in D melanogaster Genetics 144 1297–1307

    Google Scholar 

  • H Akashi (1999a) ArticleTitleInferring the fitness effects of DNA mutations from polymorphism and divergence data: Statistical power to detect directional selection under stationarity and free recombination Genetics 151 221–238

    Google Scholar 

  • H Akashi (1999b) ArticleTitleWithin- and between-species DNA sequence variation and the ‘footprint’ of natural selection Gene 238 39–51

    Google Scholar 

  • H Akashi SW Schaeffer (1997) ArticleTitleNatural selection and the frequency distributions of “silent” DNA polymorphism in Drosophila Genetics 146 295–307

    Google Scholar 

  • H Akashi M Kliman A Eyre-Walker (1998) ArticleTitleMutation pressure natural selection and the evolution of base composition in Drosophila Genetica 102–103 49–60

    Google Scholar 

  • SG Andersson CG Kurland (1998) ArticleTitleReductive evolution of resident genomes Trends Microbiol 6 263–268 Occurrence Handle10.1016/S0966-842X(98)01312-2 Occurrence Handle1:STN:280:DyaK1czot12nsA%3D%3D Occurrence Handle9717214

    Article  CAS  PubMed  Google Scholar 

  • P Argos MG Rossman UM Grau H Zuber G Frand JD Tratschin (1979) ArticleTitleThermal stability and protein structure Biochemistry 18 5698–5703

    Google Scholar 

  • JW Ballard M Kreitman (1994) ArticleTitleUnraveling selection in the mitochondrial genome of Drosophila Genetics 138 757–772

    Google Scholar 

  • P Baumann L Baumann CY Lai et al. (1995) ArticleTitleGenetics physiology and evolutionary relationships of the genus Buchnera: Intracellular symbionts of aphids Annu Rev Microbiol 49 55–94

    Google Scholar 

  • M Bulmer (1991) ArticleTitleThe selection-mutation-drift theory of synonymous codon usage Genetics 129 897–907 Occurrence Handle1:CAS:528:DyaK38XhsVKhtL0%3D Occurrence Handle1752426

    CAS  PubMed  Google Scholar 

  • MA Clark NA Moran P Baumann (1999) ArticleTitleSequence evolution in bacterial endosymbionts having extreme base compositions Mol Biol Evol 16 1586–1598

    Google Scholar 

  • MA Clark NA Moran P Baumann JJ Wernegreen (2000) ArticleTitleCospeciation between bacterial endosymbionts (Buchnera) and a recent radiation of aphids (Uroleucon) and pitfalls of testing for phylogenetic congruence Evolution 54 517–525

    Google Scholar 

  • FM Cohan (2002) ArticleTitleWhat are bacterial species? Annu Rev Microbiol 56 457–487 Occurrence Handle10.1146/annurev.micro.56.012302.160634 Occurrence Handle1:CAS:528:DC%2BD38Xos1GisLo%3D Occurrence Handle12142474

    Article  CAS  PubMed  Google Scholar 

  • T Collins P Wimberger G Naylor (1994) ArticleTitleCompositional bias character state bias and character state reconstruction using parsimony Syst Biol 43 482–496

    Google Scholar 

  • JM Comeron M Kreitman (2000) ArticleTitleThe correlation between intron length and recombination in Drosophila: Dynamic equilibrium between mutational and selective forces Genetics 156 1175–1190 Occurrence Handle1:CAS:528:DC%2BD3cXosFSnsbo%3D Occurrence Handle11063693

    CAS  PubMed  Google Scholar 

  • JA Eisen PC Hanawalt (1999) ArticleTitleA phylogenomic study of DNA repair genes proteins and processes Mutat Res 435 171–213 Occurrence Handle10.1016/S0921-8777(99)00050-6 Occurrence Handle1:CAS:528:DC%2BD3cXivVymug%3D%3D Occurrence Handle10606811

    Article  CAS  PubMed  Google Scholar 

  • H Ellegren NG Smith MT Webster (2003) ArticleTitleMutation rate variation in the mammalian genome Curr Opin Genet Dev 13 562–568

    Google Scholar 

  • B Ewing P Green (1998) ArticleTitleBase-calling of automated sequencer traces using phred. II. Error probabilities Genome Res 8 186–194 Occurrence Handle1:CAS:528:DyaK1cXitlWlu7g%3D Occurrence Handle9521922

    CAS  PubMed  Google Scholar 

  • A Eyre-Walker (1994) ArticleTitleDNA mismatch repair and synonymous codon evolution in mammals Mol Biol Evol 11 88–98

    Google Scholar 

  • A Eyre-Walker (1997) ArticleTitleDifferentiating between selection and mutation bias Genetics 147 1983–1987

    Google Scholar 

  • A Eyre-Walker (1998) ArticleTitleProblems with parsimony in sequences of biased base composition J Mol Evol 47 686–690

    Google Scholar 

  • A Eyre-Walker (1999) ArticleTitleEvidence of selection on silent site base composition in mammals: Potential implications for the evolution of isochores and junk DNA Genetics 152 675–683 Occurrence Handle1:CAS:528:DyaK1MXktFGgurw%3D Occurrence Handle10353909

    CAS  PubMed  Google Scholar 

  • MP Francino H Ochman (2001) ArticleTitleDeamination as the basis of strand-asymmetric evolution in transcribed Escherichia coli sequences Mol Biol Evol 18 1147–1150

    Google Scholar 

  • MP Francino L Chao MA Riley H Ochman (1996) ArticleTitleAsymmetries generated by transcription-coupled repair in enterobacterial genes Science 272 107–109

    Google Scholar 

  • JC Fromme GL Verdine (2003) ArticleTitleDNA lesion recognition by the bacterial repair enzyme MutM J Biol Chem 218 51543–51548

    Google Scholar 

  • DJ Funk L Helbling JJ Wernegreen NA Moran (2000) ArticleTitleIntraspecific phylogenetic congruence among multiple symbiont Proc R Soc Lond B Biol Sci 267 2517–2521

    Google Scholar 

  • DJ Funk JJ Wernegreen NA Moran (2001) ArticleTitleIntraspecific variation in symbiont genomes: Bottlenecks and the aphid–Buchnera association Genetics 157 477–489

    Google Scholar 

  • C Gautier (2000) ArticleTitleCompositional bias in DNA Curr Opin Genet Dev 10 656–661

    Google Scholar 

  • N Galtier P Boursot (2000) ArticleTitleA new method for locating changes in a tree reveals distinct nucleotide polymorphism vs divergence patterns in mouse mitochondrial control region J Mol Evol 50 224–231

    Google Scholar 

  • N Galtier JR Lobry (1997) ArticleTitleRelationships between genomic G + C content RNA secondary structures and optimal growth temperature in prokaryotes J Mol Evol 44 632–636

    Google Scholar 

  • R Gil B Sabater-Munoz A Latorre FJ Silva A Moya (2002) ArticleTitleExtreme genome reduction in Buchnera spp: Toward the minimal genome needed for symbiotic life Proc Natl Acad Sci USA 99 4454–4458

    Google Scholar 

  • D Gordon C Abajian P Green (1998) ArticleTitleConsed: A graphical tool for sequence finishing Genome Res 8 195–202 Occurrence Handle1:CAS:528:DyaK1cXitlWksr0%3D Occurrence Handle9521923

    CAS  PubMed  Google Scholar 

  • M Gouy C Gautier (1982) ArticleTitleCodon usage in bacteria: Correlation with gene expressivity Nucleic Acids Res 10 7055–7074

    Google Scholar 

  • DL Hartl EN Moriyama SA Sawyer (1994) ArticleTitleSelection intensity for codon bias Genetics 138 227–234

    Google Scholar 

  • E Haywood-Farmer SP Otto (2003) ArticleTitleThe evolution of genomic base composition in bacteria Evolution 57 1783–1792

    Google Scholar 

  • JT Herbeck DJ Funk PH Degnan JJ Wernegreen (2003) ArticleTitleA conservative test of genetic drift in the endosymbiotic bacterium Buchnera: Slightly deleterious mutations in the chaperonin groEL Genetics 165 1651–1660

    Google Scholar 

  • J Hey J Wakeley (1997) ArticleTitleA coalescent estimator of the population recombination rate Genetics 145 833–846 Occurrence Handle1:CAS:528:DyaK2sXmsVaktb4%3D Occurrence Handle9055092

    CAS  PubMed  Google Scholar 

  • JP Huelsenbeck F Ronquist (2001) ArticleTitleMRBAYES: Bayesian inference of phylogenetic trees Bioinformatics 17 754–755 Occurrence Handle10.1093/bioinformatics/17.8.754 Occurrence Handle1:STN:280:DC%2BD3MvotV2isw%3D%3D Occurrence Handle11524383

    Article  CAS  PubMed  Google Scholar 

  • T Ikemura (1981) ArticleTitleCorrelation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: A proposal for a synonymous codon choice that is optimal for the E. coli translational system J Mol Biol 151 389–409 Occurrence Handle1:CAS:528:DyaL38Xks1ygsA%3D%3D Occurrence Handle6175758

    CAS  PubMed  Google Scholar 

  • H Ishikawa (1989) ArticleTitleBiochemical and molecular aspects of endosymbiosis in insects Int Rev Cytol 116 1–45

    Google Scholar 

  • S Kanaya Y Yamada Y Kudo T Ikemura (1999) ArticleTitleStudies of codon usage and tRNA genes of 18 unicellular organisms and quantification of Bacillus subtilis tRNAs: Gene expression level and species-specific diversity of codon usage based on multivariate analysis Gene 238 143–155 Occurrence Handle10.1016/S0378-1119(99)00225-5 Occurrence Handle1:CAS:528:DyaK1MXntFKnu74%3D Occurrence Handle10570992

    Article  CAS  PubMed  Google Scholar 

  • S Karlin J Mrazek AM Campbell (1998) ArticleTitleCodon usages in different gene classes of the Escherichia coli genome Mol Microbiol 29 1341–1355

    Google Scholar 

  • M Kimura (1968) ArticleTitleEvolutionary rate at the molecular level Nature 217 624–626 Occurrence Handle1:CAS:528:DyaF1cXnsFSisA%3D%3D Occurrence Handle5637732

    CAS  PubMed  Google Scholar 

  • M Kimura (1983) The Neutral Theory of Molecular Evolution Cambridge University Press Cambridge

    Google Scholar 

  • RM Kliman J Hey (1993) ArticleTitleReduced natural selection associated with low recombination in Drosophila melanogaster Mol Biol Evol 10 1239–1258

    Google Scholar 

  • JD Lambert NA Moran (1998) ArticleTitleDeleterious mutations destabilize ribosomal RNA in endosymbiotic bacteria Proc Natl Acad Sci USA 95 4458–4462

    Google Scholar 

  • G Marais D Mouchiroud L Duret (2001) ArticleTitleDoes recombination improve selection on codon usage? Lessons from nematode and fly complete genomes Proc Natl Acad Sci USA 98 5688–5692 Occurrence Handle10.1073/pnas.091427698 Occurrence Handle1:CAS:528:DC%2BD3MXjs1WnsLo%3D Occurrence Handle11320215

    Article  CAS  PubMed  Google Scholar 

  • JH McDonald M Kreitman (1991) ArticleTitleAdaptive protein evolution at the Adh locus in Drosophila Nature 351 652–654 Occurrence Handle10.1038/351652a0 Occurrence Handle1:CAS:528:DyaK3MXks1yrtLs%3D Occurrence Handle1904993

    Article  CAS  PubMed  Google Scholar 

  • JH Miller (1996) ArticleTitleSpontaneous mutators in bacteria: Insights into pathways of mutagenesis and repair Annu Rev Microbiol 50 625–643

    Google Scholar 

  • A Mira NA Moran (2002) ArticleTitleEstimating population size and transmission bottlenecks in maternally transmitted endosymbiotic bacteria Microb Ecol 44 137–143

    Google Scholar 

  • NA Moran (1996) ArticleTitleAccelerated evolution and Muller’s rachet in endosymbiotic bacteria Proc Natl Acad Sci USA 93 2873–2878

    Google Scholar 

  • NA Moran (2002) ArticleTitleMicrobial minimalism: Genome reduction in bacterial pathogens Cell 108 583–586

    Google Scholar 

  • NA Moran JJ Wernegreen (2000) ArticleTitleLifestyle evolution in symbiotic bacteria: insights from genomics Tr Ecol Evol 15 321–326

    Google Scholar 

  • NA Moran MA Munson P Baumann H Ishikawa (1993) ArticleTitleA molecular clock in endosymbiotic bacteria is calibrated using the insect hosts Proc Roy Soc Lond B 253 167–171

    Google Scholar 

  • NA Moran M Kaplan M Gelsey T Murphy E Scholes (1999) ArticleTitlePhylogenetics and evolution of the aphid genus Uroleucon based on mitochondrial and nuclear DNA sequences Syst Entomol 24 85–93

    Google Scholar 

  • A Moya A Latorre B Sabater-Munoz FJ Silva (2002) ArticleTitleComparative molecular evolution of primary (Buchnera) and secondary symbionts of aphids based on two protein-coding genes J Mol Evol 55 IssueID2 127–137

    Google Scholar 

  • A Muto S Osawa (1987) ArticleTitleThe guanine and cytosine content of genomic DNA and bacterial evolution Proc Natl Acad Sci USA 84 166–169

    Google Scholar 

  • H Naya H Romero A Zavala B Alvarez H Musto (2002) ArticleTitleAerobiosis increases the genomic guanine plus cytosine content (GC%) in prokaryotes J Mol Evol 55 260–264

    Google Scholar 

  • H Ochman S Elwyn NA Moran (1999) ArticleTitleCalibrating bacterial evolution Proc Natl Acad Sci USA 96 12638–12643

    Google Scholar 

  • T Ohta (1973) ArticleTitleSlightly deleterious mutant substitutions in evolution Nature 246 96–98

    Google Scholar 

  • T Ohta (1992) ArticleTitleThe nearly neutral theory of molecular evolution Annu Rev Evol Syst 23 263–286

    Google Scholar 

  • A Pan C Dutta J Das (1998) ArticleTitleCodon usage in highly expressed genes of Haemophilus influenzae and Mycobacterium tuberculosis: Translational selection versus mutational bias Gene 215 405–413

    Google Scholar 

  • JR Powell EN Moriyama (1997) ArticleTitleEvolution of codon usage bias in Drosophila Proc Natl Acad Sci USA 94 7784–7790 Occurrence Handle10.1073/pnas.94.15.7784 Occurrence Handle1:CAS:528:DyaK2sXksl2nsbo%3D Occurrence Handle9223264

    Article  CAS  PubMed  Google Scholar 

  • C Rispe F Delmotte RCHJ Ham Particlevan A Moya (2004) ArticleTitleMutational and selective pressures on codon and amino acid usage in Buchnera the endosymbiotic bacteria of aphids Genome Res 14 IssueID1 44–53

    Google Scholar 

  • EP Rocha A Danchin (2002) ArticleTitleBase composition bias might result from competition for metabolic resources Trends Genet 18 291–294

    Google Scholar 

  • F Rodriguez-Trelles R Tarrio AJ Ayala (1999) ArticleTitleMolecular evolution and phylogeny of the Drosophila saltans species group inferred from the Xdh gene Mol Phylogenet Evol 13 110–121

    Google Scholar 

  • F Rodriguez-Trelles R Tarrio AJ Ayala (2000) ArticleTitleFluctuating mutation bias and the evolution of base composition in Drosophila J Mol Evol 50 1–10

    Google Scholar 

  • SA Sawyer DL Hartl (1992) ArticleTitlePopulation genetics of polymorphism and divergence Genetics 132 1161–1176

    Google Scholar 

  • PM Sharp G Matassi (1994) ArticleTitleCodon usage and genome evolution Curr Opin Genet Dev 4 851–860

    Google Scholar 

  • PM Sharp E Cowe DG Higgins et al. (1988) ArticleTitleCodon usage patterns in Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, and Homo sapiens: A review of the considerable within-species diversity Nucleic Acids Res 16 8207–8211

    Google Scholar 

  • DC Shields PM Sharp SG Higgins F Wright (1988) ArticleTitle“Silent” sites in Drosophila genes are not neutral: Evidence of selection among synonymous codons Mol Biol Evol 5 704–716 Occurrence Handle1:CAS:528:DyaL1MXitVym Occurrence Handle3146682

    CAS  PubMed  Google Scholar 

  • S Shigenobu H Watanabe M Hattori Y Sakaki H Ishikawa (2000) ArticleTitleGenome sequence of the endocellular bacterial symbiont of aphids Buchnera sp APS Nature 407 81–86 Occurrence Handle10.1038/35024074

    Article  Google Scholar 

  • NG Smith A Eyre-Walker (2002) ArticleTitleThe compositional evolution of the murid genome J Mol Evol 55 197–201

    Google Scholar 

  • NG Smith MT Webster H Ellegren (2002) ArticleTitleDeterministic mutation rate variation in the human genome Genome Res 12 1350–1356

    Google Scholar 

  • N Sueoka (1988) ArticleTitleDirectional mutation pressure and neutral molecular evolution Proc Natl Acad Sci USA 85 2653–2657

    Google Scholar 

  • N Sueoka (1993) ArticleTitleDirectional mutational pressure mutator mutations and dynamics of molecular evolution J Mol Evol 37 137–153

    Google Scholar 

  • N Sueoka (1999) ArticleTitleTranslation-coupled violation of Parity Rule 2 in human genes is not the cause of heterogeneity of the DNA G+C content of third codon position Gene 238 53–58

    Google Scholar 

  • N Suoeka (1961) ArticleTitleCorrelation between base composition of DNA and amino acid composition of proteins Proc Natl Acad Sci USA 47 1141–1149

    Google Scholar 

  • T Takano-Shimizu (2001) ArticleTitleLocal changes in GC/AT substitution biases and in crossover frequencies on Drosophila chromosomes Mol Biol Evol 18 606–619

    Google Scholar 

  • I Tamas L Klasson B Canback et al. (2002) ArticleTitle50 million years of genomic stasis in endosymbiotic bacteria Science 296 2376–2379

    Google Scholar 

  • K Tamura M Nei (1993) ArticleTitleEstimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees Mol Biol Evol 10 512–526 Occurrence Handle1:CAS:528:DyaK3sXks1CksL4%3D Occurrence Handle8336541

    CAS  PubMed  Google Scholar 

  • A Wada A Suyama (1986) ArticleTitleLocal stability of DNA and RNA secondary structure and its relation to biological functions Prog Biophys Mol Biol 47 113–157

    Google Scholar 

  • D Wang DA Kreutzer JM Essigmann (1998) ArticleTitleMutagenicity and repair of oxidative DNA damage:insights from studies using defined lesions Mutat Res 400 99–115

    Google Scholar 

  • JJ Wernegreen NA Moran (1999) ArticleTitleEvidence for genetic drift in endosymbionts (Buchnera): Analyses of protein-coding genes Mol Biol Evol 16 83–97

    Google Scholar 

  • JJ Wernegreen NA Moran (2001) ArticleTitleVertical transmission of biosynthetic plasmids in aphid endosymbionts (Buchnera) J Bacteriol 183 785–790

    Google Scholar 

  • Z Yang (1997) ArticleTitlePAML: A program package for phylogenetic analysis by maximum likelihood Comput Appl Biosci 13 555–556 Occurrence Handle1:CAS:528:DyaK2sXntlGnu7s%3D Occurrence Handle9367129

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Jonas Sandström and Nancy Moran for collecting the Uroleucon samples used in the interspecific analysis, and Paul Baumann for DNA extractions of several of these isolates. We are grateful to Steve Pennings for providing the Georgia isolate of U. ambrosiae, thank David McCauley for discussion of statistical issues, and are indebted to two anonymous reviewers for helpful comments on an earlier version of this paper. We appreciate the helpful advice and correspondence of Nancy Moran, Nicolas Galtier, Hiroshi Akashi, and Adam Eyre-Walker during the analyses for this study. We thank Patrick Degnan for superb technical assistance. The present study was conducted with support provided by the NIH (R01 GM62626-01), NSF (DEB 0089455), NASA Astrobiology Institute (NNA04CC04A), and Josephine Bay Paul and C. Michael Paul Foundation to J.J.W. Support to D.J.F. was provided by Vanderbilt University. DNA sequencing was performed at the Josephine Bay Paul Center’s W.M. Keck Ecological and Evolutionary Genetics Facility.

Author information

Authors and Affiliations

  1. Josephine Bay Paul Center for Comparative Molecular Biology & Evolution, The Marine Biological Laboratory, 7 MBL Street, Woods Hole, MA, 02543, USA

    Jennifer J. Wernegreen

  2. Department of Biological Sciences, Vanderbilt University, Nashville, TN, 3723, USA

    Daniel J. Funk

Authors
  1. Jennifer J. Wernegreen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel J. Funk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jennifer J. Wernegreen.

Additional information

Reviewing Editor: Dr. J. William Ballard

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wernegreen, J.J., Funk, D.J. Mutation Exposed: A Neutral Explanation for Extreme Base Composition of an Endosymbiont Genome. J Mol Evol 59, 849–858 (2004). https://doi.org/10.1007/s00239-003-0192-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-003-0192-z

Keywords

Search

Navigation