{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:02:23Z","timestamp":1782543743323,"version":"3.54.5"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T00:00:00Z","timestamp":1323907200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1002302","type":"journal-article","created":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T21:44:17Z","timestamp":1323985457000},"page":"e1002302","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":73,"title":["Predictability of Evolutionary Trajectories in Fitness Landscapes"],"prefix":"10.1371","volume":"7","author":[{"given":"Alexander E.","family":"Lobkovsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri I.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene V.","family":"Koonin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2011,12,15]]},"reference":[{"key":"ref1","article-title":"Full House: The spread of excellence from Plato to Darwin","author":"SJ Gould","year":"1997"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s00114-009-0607-9","article-title":"The predictability of evolution: glimpses into a post-Darwinian world.","volume":"96","author":"MS Conway","year":"2009","journal-title":"Naturwissenschaften"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1098\/rstb.2009.0154","article-title":"Evolution: like any other science it is predictable.","volume":"365","author":"SC Morris","year":"2010","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrg2810","article-title":"Constraints and plasticity in genome and molecular-phenome evolution.","volume":"11","author":"EV Koonin","year":"2010","journal-title":"Nat Rev Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/37108","article-title":"Test of synergistic interactions among deleterious mutations in bacteria.","volume":"390","author":"SF Elena","year":"1997","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jmb.2009.07.015","article-title":"Epistasis among deleterious mutations in the hiv-1 protease.","volume":"392","author":"M Parera","year":"2009","journal-title":"Mol Biol Evol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e1000742","DOI":"10.1371\/journal.pgen.1000742","article-title":"The fitness effects of random mutations in single-stranded dna and rna bacteriophages.","volume":"5","author":"P Domingo-Calap","year":"2009","journal-title":"PLoS Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1126\/science.1133479","article-title":"Direct demonstration of an adaptive constraint.","volume":"314","author":"SP Miller","year":"2006","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1126\/science.1115649","article-title":"The biochemical architecture of an ancient adaptive landscape.","volume":"310","author":"M Lunzer","year":"2005","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1471-2148-7-60","article-title":"Analysis of epistatic interactions and fitness landscapes using a new geometric approach.","volume":"7","author":"N Beerenwinkel","year":"2007","journal-title":"BMC Evol Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/ng1998","article-title":"Distributions of epistasis in microbes fit predictions from a fitness landscape model.","volume":"39","author":"G Martin","year":"2007","journal-title":"Nat Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e1001162","DOI":"10.1371\/journal.pgen.1001162","article-title":"Pervasive cryptic epistasis in molecular evolution.","volume":"6","author":"M Lunzer","year":"2010","journal-title":"PloS Genet"},{"key":"ref13","first-page":"1165","article-title":"Perspective: Sign epistasis and genetic constraint on evolutionary trajectories.","volume":"59","author":"DM Weinreich","year":"2005","journal-title":"Evolution"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0065-3233(01)55003-2","article-title":"Rational evolutionary design: the theory of in vitro protein evolution.","volume":"55","author":"CA Voigt","year":"2000","journal-title":"Adv Protein Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/nature05385","article-title":"Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein.","volume":"444","author":"S Bershtein","year":"2006","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.cbpa.2009.01.017","article-title":"Directed enzyme evolution: climbing fitness peaks one amino acid at a time.","volume":"13","author":"CA Tracewell","year":"2009","journal-title":"Curr Opin Chem Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/nrm2805","article-title":"Exploring protein fitness landscapes by directed evolution.","volume":"10","author":"PA Romero","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"18638","DOI":"10.1073\/pnas.0905497106","article-title":"The dynamics of adaptation on correlated fitness landscapes.","volume":"106","author":"S Kryazhimskiy","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-5193(89)80019-0","article-title":"The NK model of rugged fitness landscapes and its application to maturation of the immune-response.","volume":"141","author":"SA Kauffman","year":"1989","journal-title":"J Theor Biol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1371\/journal.pone.0000096","article-title":"Experimental rugged fitness landscape in protein sequence space.","volume":"1","author":"Y Hayashi","year":"2006","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1073\/pnas.0914023107","article-title":"Specificity landscapes of dna binding molecules elucidate biological function.","volume":"107","author":"CD Carlson","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1093\/nar\/gkn899","article-title":"Array-based evolution of dna aptamers allows modelling of an explicit sequence-fitness landscape.","volume":"37","author":"CG Knight","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1093\/bioinformatics\/btq353","article-title":"Predictive models for population performance on real biological fitness landscapes.","volume":"26","author":"W Rowe","year":"2010","journal-title":"Bioinformatics"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1098\/rsif.2009.0193","article-title":"Analysis of a complete dna-protein affinity landscape.","volume":"7","author":"W Rowe","year":"2010","journal-title":"J R Soc Interface"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1126\/science.1123539","article-title":"Darwinian evolution can follow only very few mutational paths to fitter proteins.","volume":"312","author":"DM Weinreich","year":"2006","journal-title":"Science"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"12025","DOI":"10.1073\/pnas.0905922106","article-title":"Stepwise acquisition of pyrimethamine resistance in the malaria parasite.","volume":"106","author":"ER Lozovsky","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e1000735","DOI":"10.1371\/journal.ppat.1000735","article-title":"Evolutionary trajectories of beta-lactamase ctx-m-1 cluster enzymes: predicting antibiotic resistance.","volume":"6","author":"A Novais","year":"2010","journal-title":"PLoS Pathog"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nchembio.113","article-title":"Quantitative exploration of the catalytic landscape separating divergent plant sesquiterpene synthases.","volume":"4","author":"PE O'Maille","year":"2008","journal-title":"Nat Chem Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nature05451","article-title":"Empirical fitness landscapes reveal accessible evolutionary paths.","volume":"445","author":"FJ Poelwijk","year":"2007","journal-title":"Nature"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/10409230903039658","article-title":"Revealing evolutionary pathways by fitness landscape reconstruction.","volume":"44","author":"M Kogenaru","year":"2009","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"026105","DOI":"10.1063\/1.3453602","article-title":"Multiple peaks and reciprocal sign epistasis in an empirically determined genotype-phenotype landscape.","volume":"20","author":"A Dawid","year":"2010","journal-title":"Chaos"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jtbi.2010.12.015","article-title":"Reciprocal sign epistasis is a necessary condition for multi-peaked fitness landscapes.","volume":"272","author":"FJ Poelwijk","year":"2011","journal-title":"J Theor Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1073\/pnas.0906192106","article-title":"Colloquium papers: Adaptive landscapes and protein evolution.","volume":"107","author":"M Carneiro","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1073\/pnas.0910445107","article-title":"Universal distribution of protein evolution rates as a consequence of protein folding physics.","volume":"107","author":"AE Lobkovsky","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cell.2008.05.042","article-title":"Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution.","volume":"134","author":"DA Drummond","year":"2008","journal-title":"Cell"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrg2662","article-title":"The evolutionary consequences of erroneous protein synthesis.","volume":"10","author":"DA Drummond","year":"2009","journal-title":"Nat Rev Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1093\/gbe\/evq010","article-title":"Relative contributions of intrinsic structural-functional constraints and translation rate to the evolution of protein-coding genes.","volume":"2","author":"YI Wolf","year":"2010","journal-title":"Genome Biol Evol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1093\/genetics\/47.6.713","article-title":"On probability of fixation of mutant genes in a population.","volume":"47","author":"M Kimura","year":"1962","journal-title":"Genetics"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1098\/rspb.2007.1137","article-title":"Robustness and evolvability: a paradox resolved.","volume":"275","author":"A Wagner","year":"2008","journal-title":"Proc Biol Sci"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature08694","article-title":"Mutational robustness can facilitate adaptation.","volume":"463","author":"JA Draghi","year":"2010","journal-title":"Nature"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.tig.2010.06.002","article-title":"Robustness and evolvability.","volume":"26","author":"J Masel","year":"2010","journal-title":"Trends Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1073\/pnas.95.10.5545","article-title":"On the thermodynamic hypothesis of protein folding.","volume":"95","author":"S Govindarajan","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1006\/jmbi.2001.5226","article-title":"Why are proteins so robust to site mutations?","volume":"315","author":"DM Taverna","year":"2002","journal-title":"J Mol Biol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1002\/prot.22964","article-title":"The evolution and evolutionary consequences of marginal thermostability in proteins.","volume":"79","author":"RA Goldstein","year":"2011","journal-title":"Proteins"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1073\/pnas.0306638101","article-title":"Imprint of evolution on protein structures.","volume":"101","author":"G Tiana","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1021\/cr040425u","article-title":"Protein folding thermodynamics and dynamics: Where physics, chemistry, and biology meet.","volume":"106","author":"E Shakhnovich","year":"2006","journal-title":"Chem Rev"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"16152","DOI":"10.1073\/pnas.0705366104","article-title":"Protein stability imposes limits on organism complexity and speed of molecular evolution.","volume":"104","author":"KB Zeldovich","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev.physchem.58.032806.104449","article-title":"Understanding protein evolution: From protein physics to Darwinian selection.","volume":"59","author":"KB Zeldovich","year":"2008","journal-title":"Ann Rev Phys Chem"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1006\/jtbi.1999.0975","article-title":"Neutral evolution of model proteins: diffusion in sequence space and overdispersion.","volume":"200","author":"U Bastolla","year":"1999","journal-title":"J Theor Biol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1471-2148-6-43","article-title":"A protein evolution model with independent sites that reproduces site-specific amino acid distributions from the Protein Data Bank.","volume":"6","author":"U Bastolla","year":"2006","journal-title":"BMC Evol Biol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/iub.223","article-title":"Protein folding simulations: from coarse-grained model to all-atom model.","volume":"61","author":"J Zhang","year":"2009","journal-title":"IUIBMB Life"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1146\/annurev.biochem.73.011303.073904","article-title":"Using protein folding rates to test protein folding theories.","volume":"73","author":"B Gillespie","year":"2004","journal-title":"Annu Rev Biochem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"521","DOI":"10.2174\/138920307783018695","article-title":"Understanding the folding rates and folding nuclei of globular proteins.","volume":"8","author":"AV Finkelstein","year":"2007","journal-title":"Curr Protein Pept Sci"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/(SICI)1097-0282(200007)54:1<64::AID-BIP70>3.0.CO;2-R","article-title":"Analysis of a local fitness landscape with a model of the rough Mt. Fuji-type landscape: application to prolyl endopeptidase and thermolysin.","volume":"54","author":"T Aita","year":"2000","journal-title":"Biopolymers"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T19:26:07Z","timestamp":1640028367000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002302"}},"subtitle":[],"editor":[{"given":"Eugene I.","family":"Shakhnovich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2011,12,15]]},"references-count":54,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2011,12,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002302","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,15]]}}}