Skip to main content
SpringerLink
Log in

Molecular Signatures Identify a Candidate Target of Balancing Selection in an arcD-Like Gene of Staphylococcus epidermidis

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

Abstract

A comparative population genetics study revealed high levels of nucleotide polymorphism and intermediate-frequency alleles in an arcC gene of Staphylococcus epidermidis, but not in a homologous gene of the more aggressive human pathogen, Staphylococcus aureus. Further investigation showed that the arcC genes used in the multilocus sequence typing schemes of these two species were paralogs. Phylogenetic analyses of arcC-containing loci, including the arginine catabolic mobile element, from both species, suggested that these loci had an eventful history involving gene duplications, rearrangements, deletions, and horizontal transfers. The peak signatures in the polymorphic S. epidermidis locus were traced to an arcD-like gene adjacent to arcC; these signatures consisted of unusually elevated Tajima’s D and π/K ratios, which were robust to assumptions about recombination and species divergence time and among the most elevated in the S. epidermidis genome. Amino acid polymorphisms, including one that differed in polarity and hydropathy, were located in the peak signatures and defined two allelic lineages. Recombination events were detected between these allelic lineages and potential donors and recipients of S. epidermidis were identified in each case. By comparison, the orthologous gene of S. aureus showed no unusual signatures. The ArcD-like protein belonged to the unknown ion transporter 3 family and appeared to be unrelated to ArcD from the arginine deiminase pathway. These studies report the first comparative population genetics results for staphylococci and the first statistical evidence for a candidate target of balancing selection in S. epidermidis.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Andrés AM, Hubisz MJ, Indap A, Torgerson DG, Degenhardt JD, Boyko AR, Gutenkunst RN, White TJ, Green ED, Bustamante CD, Clark AG, Nielsen R (2009) Targets of balancing selection in the human genome. Mol Biol Evol 26:2755–2764

    Article  PubMed  Google Scholar 

  • Beaumont MA, Zhang W, Balding DJ (2002) Approximate Bayesian computation in population genetics. Genetics 162:2025–2035

    PubMed  Google Scholar 

  • Boucher H, Miller LG, Razonable RR (2010) Serious infections caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis 51:S183–S197

    Article  PubMed  CAS  Google Scholar 

  • Brisson D, Dykhuizen DE (2004) ospC diversity in Borrelia burgdorferi. Genetics 168:713–722

    Article  PubMed  CAS  Google Scholar 

  • Camus-Kulandaivelu L, Chevin LM, Tollon-Cordet C, Charcosset A, Manicacci D, Tenaillon MI (2008) Patterns of molecular evolution associated with two selective sweeps in the Tb1-Dwarf8 region in maize. Genetics 180:1107–1121

    Article  PubMed  CAS  Google Scholar 

  • Castresana J (2000) Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 17:540–552

    Article  PubMed  CAS  Google Scholar 

  • Castric V, Bechsgaard J, Schierup MH, Vekemans X (2008) Repeated adaptive introgression at a gene under multiallelic balancing selection. PLoS Genet 4:e1000168

    Article  PubMed  Google Scholar 

  • Charlesworth D (2006) Balancing selection and its effects on sequences in nearby genome regions. PLoS Genet 2:e64

    Article  PubMed  Google Scholar 

  • Chen JS, Reddy V, Chen JH, Shlykov MA, Zheng WH, Cho J, Yen MR, Saier MH Jr (2011) Phylogenetic characterization of transport protein superfamilies: superiority of SuperfamilyTree programs over those based on multiple alignments. J Mol Microbiol Biotechnol 21:83–96

    Article  PubMed  CAS  Google Scholar 

  • Chevin LM, Billiard S, Hospital F (2008) Hitchhiking both ways: effect of two interfering selective sweeps on linked neutral variation. Genetics 180:301–316

    Article  PubMed  Google Scholar 

  • Darling AE, Mau B, Perna NT (2010) progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One 5:e11147

    Article  PubMed  Google Scholar 

  • Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, Dufayard JF, Guindon S, Lefort V, Lescot M, Claverie JM, Gascuel O (2008) Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res 36:W465–W469

    Article  PubMed  CAS  Google Scholar 

  • Didelot X, Falush D (2007) Inference of bacterial microevolution using multilocus sequence data. Genetics 175:1251–1266

    Article  PubMed  CAS  Google Scholar 

  • Didelot X, Maiden MC (2010) Impact of recombination on bacterial evolution. Trends Microbiol 18:315–322

    Article  PubMed  CAS  Google Scholar 

  • Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, Lin F, Lin J, Carleton HA, Mongodin EF, Sensabaugh GF, Perdreau-Remington F (2006) Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367:731–739

    Article  PubMed  CAS  Google Scholar 

  • Diep BA, Stone GG, Basuino L, Graber CJ, Miller A, des Etages SA, Jones A, Palazzolo-Ballance AM, Perdreau-Remington F, Sensabaugh GF, DeLeo FR, Chambers HF (2008) The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus. J Infect Dis 197:1523–1530

    Article  PubMed  CAS  Google Scholar 

  • Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797

    Article  PubMed  CAS  Google Scholar 

  • Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG (2000) Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol 38:1008–1015

    PubMed  CAS  Google Scholar 

  • Evans PD, Mekel-Bobrov N, Vallender EJ, Hudson RR, Lahn BT (2006) Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage. Proc Natl Acad Sci USA 103:18178–18183

    Article  PubMed  CAS  Google Scholar 

  • Fay JC, Wu CI (2000) Hitchhiking under positive Darwinian selection. Genetics 155:1405–1413

    PubMed  CAS  Google Scholar 

  • Feil EJ, Cooper JE, Grundmann H, Robinson DA, Enright MC, Berendt T, Peacock SJ, Smith JM, Murphy M, Spratt BG, Moore CE, Day NPJ (2003) How clonal is Staphylococcus aureus? J Bacteriol 185:3307–3316

    Article  PubMed  CAS  Google Scholar 

  • Foster TJ (2005) Immune evasion by staphylococci. Nat Rev Microbiol 3:948–958

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli M, Cagliani R, Riva S, Pozzoli U, Biasin M, Piacentini L, Comi GP, Bresolin N, Clerici M, Sironi M (2010) Population genetics of IFIH1: ancient population structure, local selection, and implications for susceptibility to type 1 diabetes. Mol Biol Evol 27:2555–2566

    Article  PubMed  CAS  Google Scholar 

  • Gill SR, Fouts DE, Archer GL et al (2005) Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J Bacteriol 187:2426–2438

    Article  PubMed  CAS  Google Scholar 

  • Gordo I, Gomes MG, Reis DG, Campos PR (2009) Genetic diversity in the SIR model of pathogen evolution. PLoS One 4:e4876

    Article  PubMed  Google Scholar 

  • Grundmann H, Hori S, Tanner G (2001) Determining confidence intervals when measuring genetic diversity and the discriminatory abilities of typing methods for microorganisms. J Clin Microbiol 39:4190–4192

    Article  PubMed  CAS  Google Scholar 

  • Hiwatashi T, Okabe Y, Tsutsui T, Melin AD, Oota H, Schaffner CM, Aureli F, Fedigan LM, Innan H, Kawamura S (2010) An explicit signature of balancing selection for color-vision variation in new world monkeys. Mol Biol Evol 27:453–464

    Article  PubMed  CAS  Google Scholar 

  • Hudson RR (2002) Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinfomatics 18:337–338

    Article  CAS  Google Scholar 

  • Hudson RR, Kreitman M, Aguadé M (1987) A test of neutral molecular evolution based on nucleotide data. Genetics 116:153–159

    PubMed  CAS  Google Scholar 

  • Ingvarsson PK (2004) Population subdivision and the Hudson–Kreitman–Aguade test: testing for deviations from the neutral model in organelle genomes. Genet Res 83:31–39

    Article  PubMed  CAS  Google Scholar 

  • Innan H (2006) Modified Hudson–Kreitman–Aguadé test and two-dimensional evaluation of neutrality tests. Genetics 173:1725–1733

    Article  PubMed  CAS  Google Scholar 

  • Joshi GS, Spontak JS, Klapper DG, Richardson AR (2011) Arginine catabolic mobile element encoded speG abrogates the unique hypersensitivity of Staphylococcus aureus to exogenous polyamines. Mol Microbiol 82:19–20

    Article  Google Scholar 

  • Kozitskaya S, Olson ME, Fey PD, Witte W, Ohlsen K, Ziebuhr W (2005) Clonal analysis of Staphylococcus epidermidis isolates carrying or lacking biofilm-mediating genes by multilocus sequence typing. J Clin Microbiol 43:4751–4757

    Article  PubMed  CAS  Google Scholar 

  • Kreitman M (2000) Methods to detect selection in populations with application to the human. Annu Rev Genomics Hum Genet 1:539–559

    Article  PubMed  CAS  Google Scholar 

  • Kreitman M, Di Rienzo A (2004) Balancing claims for balancing selection. Trends Genet 20:300–304

    Article  PubMed  CAS  Google Scholar 

  • Kuroda M, Ohta T, Uchiyama I et al (2001) Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357:1225–1240

    Article  PubMed  CAS  Google Scholar 

  • Kuroda M, Yamashita A, Hirakawa H, Kumano M, Morikawa K, Higashide M, Maruyama A, Inose Y, Matoba K, Toh H, Kuhara S, Hattori M, Ohta T (2005) Whole genome sequence of Staphylococcus saprophyticus reveals the pathogenesis of uncomplicated urinary tract infection. Proc Natl Acad Sci USA 102:13272–13277

    Article  PubMed  CAS  Google Scholar 

  • Librado P, Rozas J (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25:1451–1452

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Dong Y, Chen YY, Burne RA (2008) Environmental and growth phase regulation of the Streptococcus gordonii arginine deiminase genes. Appl Environ Microbiol 74:5023–5030

    Article  PubMed  CAS  Google Scholar 

  • Loader CR (1996) Local likelihood density estimation. Ann Stat 24:1602–1618

    Article  Google Scholar 

  • Lolkema JS, Slotboom DJ (2003) Classification of 29 families of secondary transport proteins into a single structural class using hydropathy profile analysis. J Mol Biol 327:901–909

    Article  PubMed  CAS  Google Scholar 

  • Makhlin J, Kofman T, Borovok I, Kohler C, Engelmann S, Cohen G, Aharonowitz Y (2007) Staphylococcus aureus ArcR controls expression of the arginine deiminase operon. J Bacteriol 189:5976–5986

    Article  PubMed  CAS  Google Scholar 

  • Martin D, Rybicki E (2000) RDP: detection of recombination amongst aligned sequences. Bioinformatics 16:562–563

    Article  PubMed  CAS  Google Scholar 

  • Martin DP, Lemey P, Lott M, Moulton V, Posada D, Lefeuvre P (2010) RDP3: a flexible and fast computer program for analyzing recombination. Bioinformatics 26:2462–2463

    Article  PubMed  CAS  Google Scholar 

  • Mathema B, Mediavilla JR, Chen L, Kreiswirth B (2009) Evolution and taxonomy of staphylococci. In: Crossley KB, Jefferson KK, Archer GL, Fowler VG (eds) Staphylococci in human disease, 2nd edn. Wiley-Blackwell, Oxford

    Google Scholar 

  • Maynard Smith J (1992) Analyzing the mosaic structure of genes. J Mol Evol 34:126–129

    Google Scholar 

  • Miragaia M, Thomas JC, Couto I, Enright MC, de Lencastre H (2007) Inferring a population structure for Staphylococcus epidermidis from multilocus sequence typing data. J Bacteriol 189:2540–2552

    Article  PubMed  CAS  Google Scholar 

  • Miragaia M, de Lencastre H, Perdreau-Remington F, Chambers HF, Higashi J, Sullam PM, Lin J, Wong KI, King KA, Otto M, Sensabaugh GF, Diep BA (2009) Genetic diversity of arginine catabolic mobile element in Staphylococcus epidermidis. PLoS One 4:e7722

    Article  PubMed  Google Scholar 

  • Montgomery CP, Boyle-Vavra S, Daum RS (2009) The arginine catabolic mobile element is not associated with enhanced virulence in experimental invasive disease caused by the community-associated methicillin-resistant Staphylococcus aureus USA300 genetic background. Infect Immun 77:2650–2656

    Article  PubMed  CAS  Google Scholar 

  • Ochola LI, Tetteh KK, Stewart LB, Riitho V, Marsh K, Conway DJ (2010) Allele frequency-based and polymorphism-versus-divergence indices of balancing selection in a new filtered set of polymorphic genes in Plasmodium falciparum. Mol Biol Evol 27:2344–2351

    Article  PubMed  CAS  Google Scholar 

  • Otto M (2009) Staphylococcus epidermidis—the ‘accidental’ pathogen. Nat Rev Microbiol 7:555–567

    Article  PubMed  CAS  Google Scholar 

  • Padhukasahasram B, Marjoram P, Nordborg M (2004) Estimating the rate of gene conversion on human chromosome 21. Am J Hum Genet 75:386–397

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Losada M, Browne EB, Madsen A, Wirth T, Viscidi RP, Crandall KA (2006) Population genetics of microbial pathogens estimated from multilocus sequence typing (MLST) data. Infect Genet Evol 6:97–112

    Article  PubMed  Google Scholar 

  • Plagnol V, Wall JD (2006) Possible ancestral structure in human populations. PLoS Genet 2:e105

    Article  PubMed  Google Scholar 

  • Posada D, Crandall KA (2001) Evaluation of methods for detecting recombination from DNA sequences: computer simulations. Proc Natl Acad Sci USA 98:13757–13762

    Article  PubMed  CAS  Google Scholar 

  • Prakash S, Cooper G, Singhi S, Saier MH Jr (2003) The ion transporter superfamily. Biochim Biophys Acta 1618:79–92

    Article  PubMed  CAS  Google Scholar 

  • Przeworski M, Coop G, Wall JD (2005) The signature of positive selection on standing genetic variation. Evolution 59:2312–2323

    Article  PubMed  Google Scholar 

  • Rambaut A, Grassly NC (1997) Seq-Gen: an application for the Monte Carlo simulation of DNA sequence evolution along phylogenetic trees. Comput Appl Biosci 13:235–238

    PubMed  CAS  Google Scholar 

  • Richman A (2000) Evolution of balanced genetic polymorphism. Mol Ecol 9:1953–1963

    Article  PubMed  CAS  Google Scholar 

  • Ruimy R, Maiga A, Armand-Lefevre L, Maiga I, Diallo A, Koumaré AK, Ouattara K, Soumaré S, Gaillard K, Lucet JC, Andremont A, Feil EJ (2008) The carriage population of Staphylococcus aureus from Mali is composed of a combination of pandemic clones and the divergent Panton-Valentine leukocidin-positive genotype ST152. J Bacteriol 190:3962–3968

    Article  PubMed  CAS  Google Scholar 

  • Saier MH Jr, Tran CV, Barabote RD (2006) TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Res 34:D181–D186

    Article  PubMed  CAS  Google Scholar 

  • Sawyer SA (1989) Statistical tests for detecting gene conversion. Mol Biol Evol 6:526–538

    PubMed  CAS  Google Scholar 

  • Smyth DS, Robinson DA (2010) Population genetics of Staphylococcus. In: Robinson DA, Falush D, Feil EJ (eds) Bacterial population genetics in infectious disease, 1st edn. Wiley-Blackwell, New Jersey

    Google Scholar 

  • Smyth DS, Wong A, Robinson DA (2011) Cross-species spread of SCCmec IV subtypes in staphylococci. Infect Genet Evol 11:446–451

    Article  PubMed  Google Scholar 

  • Storz JF, Wheat CW (2010) Integrating evolutionary and functional approaches to infer adaptation at specific loci. Evolution 64:2489–2509

    Article  PubMed  CAS  Google Scholar 

  • Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595

    PubMed  CAS  Google Scholar 

  • Takeuchi F, Watanabe S, Baba T, Yuzawa H, Ito T, Morimoto Y, Kuroda M, Cui L, Takahashi M, Ankai A, Baba S, Fukui S, Lee JC, Hiramatsu K (2005) Whole-genome sequencing of Staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species. J Bacteriol 187:7292–7308

    Article  PubMed  CAS  Google Scholar 

  • Thomas JC, Vargas MR, Miragaia M, Peacock SJ, Archer GL, Enright MC (2007) An improved multilocus sequence typing scheme for Staphylococcus epidermidis. J Clin Microbiol 45:616–619

    Article  PubMed  Google Scholar 

  • Thomas JC, Godfrey PA, Feldgarden M, Robinson DA (2012) Candidate targets of balancing selection in the genome of Staphylococcus aureus. Mol Biol Evol 29:1175–1186

    Article  PubMed  CAS  Google Scholar 

  • Thornton K, Andolfatto P (2006) Approximate Bayesian inference reveals evidence for a recent, severe bottleneck in a Netherlands population of Drosophila melanogaster. Genetics 172:1607–1619

    Article  PubMed  CAS  Google Scholar 

  • van Belkum A, Melles DC, Nouwen J, van Leeuwen WB, van Wamel W, Vos MC, Wertheim HFL, Verbrugh HA (2009) Co-evolutionary aspects of human colonisation and infection by Staphylococcus aureus. Infect Genet Evol 9:32–47

    Article  PubMed  Google Scholar 

  • Verhoogt HJ, Smit H, Abee T, Gamper M, Driessen AJ, Haas D, Konings WN (1992) arcD, the first gene of the arc operon for anaerobic arginine catabolism in Pseudomonas aeruginosa, encodes an arginine–ornithine exchanger. J Bacteriol 174:1568–1573

    PubMed  CAS  Google Scholar 

  • Vilella AJ, Blanco-Garcia A, Hutter S, Rozas J (2005) VariScan: analysis of evolutionary patterns from large-scale DNA sequence polymorphism data. Bioinformatics 21:2791–2793

    Article  PubMed  CAS  Google Scholar 

  • von Eiff C, Peters G, Heilmann C (2002) Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infect Dis 2:677–685

    Article  Google Scholar 

  • Vos M, Didelot X (2009) A comparison of homologous recombination rates in bacteria and archaea. ISME J 3:199–208

    Article  PubMed  CAS  Google Scholar 

  • Watterson GA (1975) Number of segregating sites in genetics models without recombination. Theor Popul Biol 7:256–276

    Article  PubMed  CAS  Google Scholar 

  • Weedall GD, Conway DJ (2010) Detecting signatures of balancing selection to identify targets of anti-parasite immunity. Trends Parasitol 26:363–369

    Article  PubMed  CAS  Google Scholar 

  • Wildschutte H, Lawrence JG (2007) Differential Salmonella survival against communities of intestinal amoebae. Microbiology 41:10095–10104

    Google Scholar 

  • Wiuf C, Zhao K, Innan H, Nordborg M (2004) The probability and chromosomal extent of trans-specific polymorphism. Genetics 168:2363–2372

    Article  PubMed  Google Scholar 

  • Wong A, Reddy SP, Smyth DS, Aguero-Rosenfeld ME, Sakoulas G, Robinson DA (2010) Polyphyletic emergence of linezolid-resistant staphylococci in the United States. Antimicrob Agents Chemother 54:742–748

    Article  PubMed  CAS  Google Scholar 

  • Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J, Qin ZQ, Miao YG, Wang WY, Chen RS, Shen Y, Chen Z, Yuan ZH, Zhao GP, Qu D, Danchin A, Wen YM (2003) Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228). Mol Microbiol 49:1577–1593

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y, Weiss EC, Otto M, Fey PD, Smeltzer MS, Somerville GA (2007) Staphylococcus aureus biofilm metabolism and the influence of arginine on polysaccharide intercellular adhesin synthesis, biofilm formation, and pathogenesis. Infect Immun 75:4219–4226

    Article  PubMed  CAS  Google Scholar 

  • Zúñiga M, Champomier-Verges M, Zagorec M, Pérez-Martínez G (1998) Structural and functional analysis of the gene cluster encoding the enzymes of the arginine deiminase pathway of Lactobacillus sake. J Bacteriol 180:4154–4159

    PubMed  Google Scholar 

  • Zúñiga M, Pérez G, González-Candelas F (2002) Evolution of arginine deiminase (ADI) pathway genes. Mol Phylogenet Evol 25:429–444

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Institutes of Health Grant GM080602 (to D.A.R.).

Author information

Authors and Affiliations

  1. Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    Liangfen Zhang, Jonathan C. Thomas & D. Ashley Robinson

  2. Department of Infectious Disease Epidemiology, Imperial College London, London, UK

    Xavier Didelot

Authors
  1. Liangfen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan C. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xavier Didelot
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Ashley Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Ashley Robinson.

Additional information

Liangfen Zhang and Jonathan C. Thomas contributed equally to this study.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Thomas, J.C., Didelot, X. et al. Molecular Signatures Identify a Candidate Target of Balancing Selection in an arcD-Like Gene of Staphylococcus epidermidis . J Mol Evol 75, 43–54 (2012). https://doi.org/10.1007/s00239-012-9520-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-012-9520-5

Keywords

Search

Navigation