{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:03:42Z","timestamp":1791079422533,"version":"4.1.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:00:00Z","timestamp":1384387200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1003766","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T22:38:47Z","timestamp":1384468727000},"page":"e1003766","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":46,"title":["Natural Selection Promotes Antigenic Evolvability"],"prefix":"10.1371","volume":"9","author":[{"given":"Christopher J.","family":"Graves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera I. D.","family":"Ros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Sniegowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin","family":"Brisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,11,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"R831","DOI":"10.1016\/j.cub.2006.08.080","article-title":"Evolvability","volume":"16","author":"PD Sniegowski","year":"2006","journal-title":"Current Biology"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"8597","DOI":"10.1073\/pnas.0702207104","article-title":"The frailty of adaptive hypotheses for the origins of organismal complexity","volume":"104 Suppl 1","author":"M Lynch","year":"2007","journal-title":"Proceedings of the National Academy of Sciences, USA"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1016\/S0960-9822(01)00041-0","article-title":"Evolution: the evolvability enigma","volume":"11","author":"JF Brookfield","year":"2001","journal-title":"Current Biology"},{"key":"ref4","unstructured":"Williams GC (1966) Adaptation and Natural Selection. Princeton, NJ: Princeton University Press."},{"key":"ref5","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1558-5646.2007.00303.x","article-title":"Evolution of evolvability in a developmental model","volume":"62","author":"J Draghi","year":"2008","journal-title":"Evolution"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S0960-9822(00)00005-1","article-title":"Adaptive evolution of highly mutable loci in pathogenic bacteria","volume":"4","author":"ER Moxon","year":"1994","journal-title":"Curr Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"7152","DOI":"10.1073\/pnas.1132114100","article-title":"Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus","volume":"100","author":"JB Plotkin","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1534\/genetics.105.040493","article-title":"Evolutionary capacitance may be favored by natural selection","volume":"170","author":"J Masel","year":"2005","journal-title":"Genetics"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/ng1618","article-title":"Intragenic tandem repeats generate functional variability","volume":"37","author":"KJ Verstrepen","year":"2005","journal-title":"Nat Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1086\/419267","article-title":"Models of parasite virulence","volume":"71","author":"SA Frank","year":"1996","journal-title":"Quarterly review of Biology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1098\/rspb.1994.0156","article-title":"Kin selection and virulence in the evolution of protocells and parasites","volume":"258","author":"SA Frank","year":"1994","journal-title":"Proc Biol Sci"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/0966-842X(94)90538-X","article-title":"Short-sighted evolution and the virulence of pathogenic microorganisms","volume":"2","author":"BR Levin","year":"1994","journal-title":"Trends in Microbiology"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Ewald PW (1994) Evolution of infectious disease. Oxford University Press.","DOI":"10.1093\/oso\/9780195060584.001.0001"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/j.1420-9101.2007.01480.x","article-title":"Mechanisms of pathogenesis and the evolution of parasite virulence","volume":"21","author":"SA Frank","year":"2008","journal-title":"Journal of Evolutionary Biology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"8472","DOI":"10.1073\/pnas.0702412104","article-title":"Simple sequence repeats in prokaryotic genomes","volume":"104","author":"J Mrazek","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1111\/j.1365-2958.2007.05895.x","article-title":"The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens","volume":"65","author":"T Bankhead","year":"2007","journal-title":"Molecular Microbiology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1128\/IAI.66.8.3689-3697.1998","article-title":"Kinetics and in vivo induction of genetic variation of <italic>vlsE<\/italic> in <italic>Borrelia burgdorferi<\/italic>","volume":"66","author":"JR Zhang","year":"1998","journal-title":"Infection and Immunity"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0092-8674(00)80206-8","article-title":"Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes","volume":"89","author":"JR Zhang","year":"1997","journal-title":"Cell"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"13865","DOI":"10.1073\/pnas.97.25.13865","article-title":"Correlation between plasmid content and infectivity in Borrelia burgdorferi","volume":"97","author":"JE Purser","year":"2000","journal-title":"Proceedings of the National Academy of Sciences of the United States of America U S A"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1128\/IAI.63.6.2206-2212.1995","article-title":"High- and low-infectivity phenotypes of clonal populations of in vitro-cultured <italic>Borrelia burgdorferi<\/italic>","volume":"63","author":"SJ Norris","year":"1995","journal-title":"Infection and Immunity"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e1000293","DOI":"10.1371\/journal.ppat.1000293","article-title":"Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of <italic>Borrelia burgdorferi<\/italic> infection","volume":"5","author":"L Coutte","year":"2009","journal-title":"PLoS Pathogens"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1046\/j.1365-2958.2003.03386.x","article-title":"Characterization of the <italic>vls<\/italic> antigenic variation loci of the Lyme disease spirochaetes <italic>Borrelia garinii<\/italic> Ip90 and <italic>Borrelia afzelii<\/italic> ACAI","volume":"47","author":"D Wang","year":"2003","journal-title":"Molecular Microbiology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"21691","DOI":"10.1074\/jbc.M201547200","article-title":"Crystal structure of Lyme disease variable surface antigen VlsE of <italic>Borrelia burgdorferi<\/italic>","volume":"277","author":"C Eicken","year":"2002","journal-title":"Journal of Biological Chemistry"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"4196","DOI":"10.1128\/IAI.70.8.4196-4203.2002","article-title":"Evidence that the variable regions of the central domain of VlsE are antigenic during infection with Lyme disease spirochetes","volume":"70","author":"JV McDowell","year":"2002","journal-title":"Infection and Immunity"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1128\/JB.01158-10","article-title":"Whole-genome sequences of thirteen isolates of Borrelia burgdorferi","volume":"193","author":"SE Schutzer","year":"2011","journal-title":"Journal of Bacteriology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/oxfordjournals.molbev.a004233","article-title":"Pervasive adaptive evolution in mammalian fertilization proteins","volume":"20","author":"WJ Swanson","year":"2003","journal-title":"Mol Biol Evol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/genetics\/155.1.431","article-title":"Codon-substitution models for heterogeneous selection pressure at amino acid sites","volume":"155","author":"Z Yang","year":"2000","journal-title":"Genetics"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.fmrre.2004.10.004","article-title":"Gene conversion and concerted evolution in bacterial genomes","volume":"29","author":"G Santoyo","year":"2005","journal-title":"FEMS Microbiol Rev"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s002390010093","article-title":"Gene conversion drives within genic sequences: concerted evolution of ribosomal RNA genes in bacteria and archaea","volume":"51","author":"D Liao","year":"2000","journal-title":"J Mol Evol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0092-8674(83)90331-8","article-title":"The double-strand-break repair model for recombination","volume":"33","author":"JW Szostak","year":"1983","journal-title":"Cell"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.dnarep.2004.03.037","article-title":"Homologous recombination-mediated double-strand break repair","volume":"3","author":"C Wyman","year":"2004","journal-title":"DNA Repair (Amst)"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e1000679","DOI":"10.1371\/journal.ppat.1000679","article-title":"Central role of the Holliday junction helicase RuvAB in vlsE recombination and infectivity of Borrelia burgdorferi","volume":"5","author":"T Lin","year":"2009","journal-title":"PLoS Pathog"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1128\/IAI.66.8.3698-3704.1998","article-title":"Genetic variation of the <italic>Borrelia burgdorferi<\/italic> gene <italic>vlsE<\/italic> involves cassette-specific, segmental gene conversion","volume":"66","author":"J-R Zhang","year":"1998","journal-title":"Infection and Immunity"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1128\/IAI.62.8.3568-3571.1994","article-title":"Expression and gene sequence of outer surface protein C of <italic>Borrelia burgdorferi<\/italic> reisolated from chronically infected mice","volume":"62","author":"B Stevenson","year":"1994","journal-title":"Infection and Immunity"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1128\/IAI.67.6.3146-3150.1999","article-title":"Stability of erp loci during Borrelia burgdorferi infection: recombination is not required for chronic infection of immunocompetent mice","volume":"67","author":"N El Hage","year":"1999","journal-title":"Infect Immun"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijmm.2007.10.002","article-title":"Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal-tick infection cycle","volume":"298 Suppl 1","author":"T Bykowski","year":"2008","journal-title":"Int J Med Microbiol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.pt.2007.07.001","article-title":"Tick-host-pathogen interactions in Lyme borreliosis","volume":"23","author":"JW Hovius","year":"2007","journal-title":"Trends Parasitol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00508-006-0690-2","article-title":"Evolving models of Lyme disease spirochete gene regulation","volume":"118","author":"B Stevenson","year":"2006","journal-title":"Wien Klin Wochenschr"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1042\/bst0310108","article-title":"Temporal regulation of outer surface proteins of the Lyme-disease spirochaete Borrelia burgdorferi","volume":"31","author":"TG Schwan","year":"2003","journal-title":"Biochem Soc Trans"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e1000304","DOI":"10.1371\/journal.pgen.1000304","article-title":"The population genetics of dN\/dS","volume":"4","author":"S Kryazhimskiy","year":"2008","journal-title":"PLoS Genet"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"W506","DOI":"10.1093\/nar\/gkm382","article-title":"Selecton 2007: advanced models for detecting positive and purifying selection using a Bayesian inference approach","volume":"35","author":"A Stern","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.mrfmmm.2006.01.020","article-title":"Mechanisms of tandem repeat instability in bacteria","volume":"598","author":"M Bichara","year":"2006","journal-title":"Mutat Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev.genet.40.110405.090442","article-title":"Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation","volume":"40","author":"R Moxon","year":"2006","journal-title":"Annu Rev Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/1521-1878(200012)22:12<1057::AID-BIES3>3.0.CO;2-W","article-title":"The evolution of mutation rates: separating causes from consequences","volume":"22","author":"PD Sniegowski","year":"2000","journal-title":"Bioessays"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1128\/IAI.61.6.2273-2276.1993","article-title":"Bacterial antigenic variation, host immune response, and pathogen-host coevolution","volume":"61","author":"RC Brunham","year":"1993","journal-title":"Infection and Immunity"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1128\/.61.3.281-293.1997","article-title":"Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections","volume":"61","author":"KW Deitsch","year":"1997","journal-title":"Microbiol Mol Biol Rev"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrmicro2145","article-title":"Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens","volume":"7","author":"KW Deitsch","year":"2009","journal-title":"Nature Reviews Microbiology"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"6077","DOI":"10.1073\/pnas.87.16.6077","article-title":"Juxtaposition of expressed variable antigen genes with a conserved telomere in the bacterium Borrelia hermsii","volume":"87","author":"T Kitten","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0092-8674(86)90489-7","article-title":"The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion","volume":"44","author":"R Haas","year":"1986","journal-title":"Cell"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/j.1365-2958.2004.04086.x","article-title":"Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection","volume":"52","author":"A Centurion-Lara","year":"2004","journal-title":"Mol Microbiol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-2958.2007.05898.x","article-title":"mgpB and mgpC sequence diversity in Mycoplasma genitalium is generated by segmental reciprocal recombination with repetitive chromosomal sequences","volume":"66","author":"SL Iverson-Cabral","year":"2007","journal-title":"Mol Microbiol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/nar\/gki198","article-title":"MAFFT version 5: improvement in accuracy of multiple sequence alignment","volume":"33","author":"K Katoh","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"W609","DOI":"10.1093\/nar\/gkl315","article-title":"PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments","volume":"34","author":"M Suyama","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref54","first-page":"418","article-title":"Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions","volume":"3","author":"M Nei","year":"1986","journal-title":"Mol Biol Evol"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Nei M, Kumar S (2000) Molecular Evolution and Phylogenetics. New York: Oxford University Press.","DOI":"10.1093\/oso\/9780195135848.001.0001"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1093\/molbev\/msr121","article-title":"MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods","volume":"28","author":"K Tamura","year":"2011","journal-title":"Mol Biol Evol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1093\/nar\/gkg617","article-title":"mreps: Efficient and flexible detection of tandem repeats in DNA","volume":"31","author":"R Kolpakov","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/bioinformatics\/bti770","article-title":"The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling","volume":"22","author":"K Arnold","year":"2006","journal-title":"Bioinformatics"},{"key":"ref59","unstructured":"Drummond AJ, Ashton B, Buxton S, Cheung M, Cooper A, <etal>et al<\/etal>.. (2010) Geneious v5.3 Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.geneious.com\" xlink:type=\"simple\">http:\/\/www.geneious.com<\/ext-link>."},{"key":"ref60","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1093\/infdis\/157.4.842","article-title":"Experimental Lyme arthritis in rats infected with Borrelia burgdorferi","volume":"157","author":"SW Barthold","year":"1988","journal-title":"J Infect Dis"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1099\/mic.0.26944-0","article-title":"Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents <italic>Borrelia burgdorferi<\/italic> in North America and <italic>Borrelia afzelii<\/italic> in Europe","volume":"150","author":"J Bunikis","year":"2004","journal-title":"Microbiology"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1003766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T12:55:49Z","timestamp":1716123349000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1003766"}},"subtitle":[],"editor":[{"given":"Richard","family":"Moxon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,11,14]]},"references-count":61,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1003766","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,14]]}}}