JosephThorntonJoseph Thornton41.78927490000000-87.601250000000001722Thornton, JosephMolecular EvolutionEvolutionary biochemistryBiochemistryPhylogeneticsEvolution, GeneticEvolutionMy lab studies the mechanisms by which protein functions evolve. We do this by phylogenetically reconstructing the histories of ancient proteins and then synthesizing, manipulating, and experimentally characterizing their biological functions and physical properties.
This kind of work is powerful and fun — and possible at all — because we are a diverse group of evolutionary biologists, biochemists, biophysicists, computational biologists, geneticists, and molecular biologists, all working together and freely mingling our expertise, techniques, and ideas.
We address classical and recent questions about the nature of evolutionary processes, such as: How do complex molecular systems evolve? Does evolution proceed by a few large-effect or many small-effect mutations? Does epistasis shape the evolutionary process and make the pathways and outcomes of evolution contingent on chance events? Is evolution reversible? How does the architecture of biological systems shape the evolutionary process? How did evolution produce those architectures in the first place?
Evolutionary analysis can also help address core questions in biochemistry, biophysics, and molecular biology. Why do proteins have the particular architectures that they do? How does that architecture itself evolve? What structural and genetic mechanisms cause functions to differ between members of protein families? How do molecular machines, allostery, and molecular interfaces evolve? Are proteins’ physical properties always optimized for their functions, and if not, why not? Can history explain why particular proteins are subject to interference by particular drugs and pollutants? We have found that detailed reconstruction of proteins’ histories helps us to understand why and how their present-day descendants work as they do today.Professorprns:awardConferredByaward conferred byprns:coAuthorOfcoauthor ofprns:emailEncryptedemail addressprns:endDateend dateprns:fullNamefull nameprns:grantAwardedBygrant awarded byprns:hasAuthorListauthor listprns:hasNetworkhas networkprns:hasPublicationVenuepublished inprns:informationResourceReferenceinformation resource referenceprns:isPrimaryPositionis primary positionprns:latitudelatitudeprns:longitudelongitudeprns:mainImagephotoprns:maxWeightmaximum weightprns:medlineTAjournal title abbreviationprns:meshDescriptorUIMeSH DescriptorUIprns:meshSemanticGroupNameMeSH semantic group nameprns:minWeightminimum weightprns:numberOfAuthorsnumber of authorsprns:numberOfConnectionsnumber of connectionsprns:numberOfPublicationsnumber of publicationsprns:personIdPerson IDprns:personInPrimaryPositionperson in primary positionprns:physicalNeighborOfphysical neighborprns:positionInDepartmentposition in departmentprns:predicateNodepredicate nodeprns:principalInvestigatorNameprincipal investigator nameprns:publicationDatepublication dateprns:similarTosimilar toprns:sortOrdersort orderprns:startDatestart dateprns:trainingAtOrganizationeducational organizationprns:trainingLocationtraining locationprns:uniquenessWeightuniqueness weightprns:yearyearAcademic ArticleArticleDocumentbibo:pmidPubMed IdentifierAddressvivo:addressCitycityvivo:addressPostalCodepostal codevivo:addressStatestate or provinceAgreementvivo:authorInAuthorshipselected publicationsvivo:authorRankauthor rank in publicationAuthorshipvivo:awardOrHonorawards and honorsAward or Honor Receiptvivo:degreeEarneddegree earnedDepartmentvivo:educationalTrainingeducation and trainingEducational Trainingvivo:freetextKeywordkeywordsGrantvivo:hasResearchArearesearch areasvivo:hasResearcherRoleresearch activitiesvivo:hrJobTitleHR job titleInformation Resourcevivo:linkAnchorTextlink anchor textvivo:linkedAuthorlinked authorvivo:linkedInformationResourcelinked information resourcevivo:mailingAddressmailing addressvivo:majorFieldmajor field of degreevivo:orcidIdORCID idvivo:overviewoverviewvivo:personInPositionpositionsPositionvivo:positionInOrganizationposition in organizationvivo:preferredTitlepreferred titleResearcher Rolevivo:researcherRoleOfresearcher role ofRolevivo:roleContributesTocontributes tovivo:sponsorAwardIdsponsor award idURLLinkvivo:webpagewebpagerdf:predicatepredicaterdf:typetyperdfs:labellabelConceptAgentfoaf:firstNamefirst namefoaf:lastNamelast nameOrganizationPersonAuthorship 1017528Authorship 101921228301769Hochberg GKA, Thornton JWAnnual review of biophysicsReconstructing Ancient Proteins to Understand the Causes of Structure and Function. Annu Rev Biophys. 2017 05 22; 46:247-269.Annu Rev Biophys2017-03-15T00:00:002017Reconstructing Ancient Proteins to Understand the Causes of Structure and Function.26790885Anderson DP, Whitney DS, Hanson-Smith V, Woznica A, Campodonico-Burnett W, Volkman BF, King N, Thornton JW, Prehoda KEeLifeCorrection: Evolution of an ancient protein function involved in organized multicellularity in animals. Elife. 2016 Jan 21; 5:e14311.Elife2016-01-21T00:00:002016Correction: Evolution of an ancient protein function involved in organized multicellularity in animals.Authorship 103222726715749Hudson WH, Kossmann BR, de Vera IM, Chuo SW, Weikum ER, Eick GN, Thornton JW, Ivanov IN, Kojetin DJ, Ortlund EAProceedings of the National Academy of Sciences of the United States of AmericaDistal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space. Proc Natl Acad Sci U S A. 2016 Jan 12; 113(2):326-31.Proc Natl Acad Sci U S A2015-12-29T00:00:002015Distal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space.BryanDickinson02tqa6gbCuPXsW9naE/t8mL1sc65/A==Bryan Dickinson41.7886000000000087.598699999999993482Dickinson, BryanProfessor Authorship 1073373Authorship 1073383Authorship 107339406/2000Columbia University/ American Museum of Natural HistoryColumbia University/ American Museum of Natural History, Biological SciencesPh.DBiological Sciences08/2012Columbia UniversityNew YorkColumbia University, Postdoc28902834Starr TN, Picton LK, Thornton JWNatureAlternative evolutionary histories in the sequence space of an ancient protein. Nature. 2017 09 21; 549(7672):409-413.Nature2017-09-13T00:00:002017Alternative evolutionary histories in the sequence space of an ancient protein.28841430Siddiq MA, Hochberg GK, Thornton JWCurrent opinion in structural biologyEvolution of protein specificity: insights from ancestral protein reconstruction. Curr Opin Struct Biol. 2017 12; 47:113-122.Curr Opin Struct Biol2017-08-23T00:00:002017Evolution of protein specificity: insights from ancestral protein reconstruction.28812605Siddiq MA, Loehlin DW, Montooth KL, Thornton JWNature ecology & evolutionExperimental test and refutation of a classic case of molecular adaptation in Drosophila melanogaster. Nat Ecol Evol. 2017 Jan 13; 1(2):25.Nat Ecol Evol2017-01-13T00:00:002017Experimental test and refutation of a classic case of molecular adaptation in Drosophila melanogaster.RamaRanganathanxWNnDKAbGPjRkHR2QFPt+2z5/syyp7BaZQ==Rama Ranganathan41.7886000000000087.598699999999993563Ranganathan, RamaProfessorBiochemistry and Molecular BiologyEcology and EvolutionOrganismal Biology and Anatomy2014Guggenheim Foundation FellowshipNational Institute for Environmental Health Sciences2014Hans Falk AwardOregon Medical Research Foundation2010Richard Jones Investigator AwardHoward Hughes Medical Institute2009Early Career Investigator2007U.S. Presidential Early Career Award for Scientists and EngineersNational Science Foundation2006CAREER Award2006Alfred P. Sloan Foundation Research FellowCarnegie-Mellon University2002Distinguished University Lecturer in Environmental SustainabilityUniversity of Wisconsin2016Steenbock Distinguished Lecturer in BiochemistryUniversity of Queensland School of Biochemistry2016Distinguished Alumni LectureshipAuthorship 1079773Authorship 107978529967485Venkat A, Hahn MW, Thornton JWNature ecology & evolutionMultinucleotide mutations cause false inferences of lineage-specific positive selection. Nat Ecol Evol. 2018 08; 2(8):1280-1288.Nat Ecol Evol2018-07-02T00:00:002018Multinucleotide mutations cause false inferences of lineage-specific positive selection.29626131Starr TN, Flynn JM, Mishra P, Bolon DNA, Thornton JWProceedings of the National Academy of Sciences of the United States of AmericaPervasive contingency and entrenchment in a billion years of Hsp90 evolution. Proc Natl Acad Sci U S A. 2018 04 24; 115(17):4453-4458.Proc Natl Acad Sci U S A2018-04-06T00:00:002018Pervasive contingency and entrenchment in a billion years of Hsp90 evolution.Authorship 1206324Authorship 123664827432813Katsu Y, Cziko PA, Chandsawangbhuwana C, Thornton JW, Sato R, Oka K, Takei Y, Baker ME, Iguchi TGeneral and comparative endocrinologyA second estrogen receptor from Japanese lamprey (Lethenteron japonicum) does not have activities for estrogen binding and transcription. Gen Comp Endocrinol. 2016 09 15; 236:105-114.Gen Comp Endocrinol2016-07-16T00:00:002016A second estrogen receptor from Japanese lamprey (Lethenteron japonicum) does not have activities for estrogen binding and transcription.30298815Liu Q, Onal P, Datta RR, Rogers JM, Schmidt-Ott U, Bulyk ML, Small S, Thornton JWeLifeAncient mechanisms for the evolution of the bicoid homeodomain's function in fly development. Elife. 2018 10 09; 7.Elife2018-10-09T00:00:002018Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development.Medicine-Computational Biomedicine and Biomedical Data ScienceAuthorship 129338631043568Cheng S, Park Y, Kurleto JD, Jeon M, Zinn K, Thornton JW, Özkan EProceedings of the National Academy of Sciences of the United States of AmericaFamily of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence. Proc Natl Acad Sci U S A. 2019 05 14; 116(20):9837-9842.Proc Natl Acad Sci U S A2019-05-01T00:00:002019Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence.Authorship 133502231594844Siddiq MA, Thornton JWProceedings of the National Academy of Sciences of the United States of AmericaFitness effects but no temperature-mediated balancing selection at the polymorphic Adh gene of Drosophila melanogaster. Proc Natl Acad Sci U S A. 2019 10 22; 116(43):21634-21640.Proc Natl Acad Sci U S A2019-10-08T00:00:002019Fitness effects but no temperature-mediated balancing selection at the polymorphic Adh gene of Drosophila melanogaster.D011506Chemicals & Drugs3127770.656427ProteinsAuthorship 1379031032461643Pillai AS, Chandler SA, Liu Y, Signore AV, Cortez-Romero CR, Benesch JLP, Laganowsky A, Storz JF, Hochberg GKA, Thornton JWNatureOrigin of complexity in haemoglobin evolution. Nature. 2020 05; 581(7809):480-485.Nature2020-05-20T00:00:002020Origin of complexity in haemoglobin evolution.Authorship 1384651032587402Pillai AS, Chandler SA, Liu Y, Signore AV, Cortez-Romero CR, Benesch JLP, Laganowsky A, Storz JF, Hochberg GKA, Thornton JWNatureAuthor Correction: Origin of complexity in haemoglobin evolution. Nature. 2020 Jul; 583(7816):E26.Nature2020-07-01T00:00:002020Author Correction: Origin of complexity in haemoglobin evolution.EnginOzkanEngin Ozkan0.000000000000000.000000000000002877Ozkan, EnginAssociate ProfessorAuthorship 142311433214251Park Y, Patton JEJ, Hochberg GKA, Thornton JWScience (New York, N.Y.)Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase". Science. 2020 11 20; 370(6519).Science2020-11-20T00:00:002020Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase".Authorship 142612633299178Hochberg GKA, Liu Y, Marklund EG, Metzger BPH, Laganowsky A, Thornton JWNatureA hydrophobic ratchet entrenches molecular complexes. Nature. 2020 12; 588(7838):503-508.Nature2020-12-09T00:00:002020A hydrophobic ratchet entrenches molecular complexes.Authorship 146864434061027Xie VC, Pu J, Metzger BP, Thornton JW, Dickinson BCeLifeContingency and chance erase necessity in the experimental evolution of ancestral proteins. Elife. 2021 06 01; 10.Elife2021-06-01T00:00:002021Contingency and chance erase necessity in the experimental evolution of ancestral proteins.D019143Phenomena1868130.635637Evolution, MolecularAuthorship 150999534731636Wang J, Vaddadi N, Pak JS, Park Y, Quilez S, Roman CA, Dumontier E, Thornton JW, Cloutier JF, Özkan ECell reportsMolecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors. Cell Rep. 2021 11 02; 37(5):109940.Cell Rep2021-11-02T00:00:002021Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors.Authorship 154890335587978Park Y, Metzger BPH, Thornton JWScience (New York, N.Y.)Epistatic drift causes gradual decay of predictability in protein evolution. Science. 2022 05 20; 376(6595):823-830.Science2022-05-19T00:00:002022Epistatic drift causes gradual decay of predictability in protein evolution.AartiVenkatAarti Venkat41.7886000000000087.598699999999994156Venkat, AartiAssistant ProfessorD011987Chemicals & Drugs23420.964194Receptors, SteroidAuthorship 159430336107026Pillai AS, Hochberg GKA, Thornton JWProtein science : a publication of the Protein SocietySimple mechanisms for the evolution of protein complexity. Protein Sci. 2022 11; 31(11):e4449.Protein Sci2022-11-01T00:00:002022Simple mechanisms for the evolution of protein complexity.ChuanHe1Gp8Cq8dHMzMknJtY0fp/Cv/+94=Chuan He0.000000000000000.000000000000003123He, ChuanProfessorhttp://pfisterlab.uchicago.eduCathy Pfister's websitehttp://www.thorntonlab.orgThornton Lab websitehttp://voices.uchicago.edu/woottonlab/Wootton Lab at the University of Chicagohttps://voices.uchicago.edu/ozkanlabThe Özkan Lab at the University of Chicagohttp://he-group.uchicago.eduMy Lab Sitehttp://sosnick.uchicago.edu/Sosnick lab websitehttps://voices.uchicago.edu/dwyerlab/Greg Dwyer Labhttp://manyuanlonglab.uchicago.edu/Long Lab Websitehttp://ranganathanlab.org/Ranganathan Labhttp://schmidtottlab.uchicago.edu/Schmidt-Ott Laboratory: Developmental Mechanisms and Evolution2025-03-31NIHBOLON, DANIEL N;THORNTON, JOSEPH W2021-06-01Comprehensive analysis of fitness effects and epistasis along a billion-year evolutionary trajectoryR01GM1390072026-06-30NIHNOVEMBRE, JOHN ;ROTHMAN-DENES, LUCIA B. B;RUTHENBURG, ALEXANDER JACKSON;THORNTON, JOSEPH W2021-07-01Genetic Mechanisms and EvolutionT32GM1397822023-08-31NIHTHORNTON, JOSEPH W2019-09-01Evolution of molecular complexes: genetic, structural, and functional mechanisms for the evolution of oligomers and allosteryR01GM1311282021-03-31NIHTHORNTON, JOSEPH W2017-04-04Deep characterization of the sequence space and evolutionary trajectories of reconstructed ancestral proteins - Resubmission 01R01GM1219312018-05-31NIHTHORNTON, JOSEPH W2013-09-17Mechanisms for the evolution of novel DNA specificity in a transcription factor fR01GM1043972013-07-31NIHTHORNTON, JOSEPH W2007-08-01Experimental and structural evolution of hormone receptorsR01GM0815922007-04-30NIHTHORNTON, JOSEPH W2004-05-01Experimental evolution of ligand-receptor relationshipsR21GM070792Principal InvestigatorPrincipal InvestigatorPrincipal InvestigatorPrincipal InvestigatorPrincipal InvestigatorPrincipal InvestigatorPrincipal InvestigatorD004843Genes & Molecular SequencesPhysiology55860.946486Epistasis, GeneticD010802Concepts & Ideas22711360.665652PhylogenyAuthorship 164092437395787Lucaci AG, Zehr JD, Enard D, Thornton JW, Kosakovsky Pond SLMolecular biology and evolutionEvolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses. Mol Biol Evol. 2023 07 05; 40(7).Mol Biol Evol2023-07-05T00:00:002023Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses.ChemistryHuman GeneticsUniversity of ChicagoJohn TimothyWootton3XZ+BK4BDeP5hHlsaUXv9Gq0+s+oJohn Timothy Wootton41.78927490000000-87.601250000000001244Wootton, John TimothyProfessor10.01580.00861226239research areas0.6716920.1711084coauthor of137.62915.945560similar to1168selected publicationsMollyPrzeworskiMolly Przeworski41.78927490000000-87.601250000000001825Przeworski, MollyPROFESSORMartinKreitman2ml7DoF1GuTQkntjbwjr93A=Martin Kreitman41.78927490000000-87.601250000000002043Kreitman, MartinProfessorAuthorship 167190937732229Park Y, Metzger BPH, Thornton JWbioRxiv : the preprint server for biologyThe simplicity of protein sequence-function relationships. bioRxiv. 2024 Feb 07.bioRxiv2024-02-07T00:00:002024The simplicity of protein sequence-function relationships.CatherinePfisterCatherine Pfister41.78927490000000-87.601250000000002376Pfister, CatherineProfessorUrs C.Schmidt-OttUrs C. Schmidt-Ott41.78927490000000-87.601250000000002507Schmidt-Ott, Urs C.0000-0002-1351-9472ProfessorGregoryDwyerGregory Dwyer41.78927490000000-87.601250000000002551Dwyer, GregoryProfessorManyuanLongManyuan Long41.78927490000000-87.601250000000002617Long, ManyuanProfessorTobin R.Sosnickw3B6BLIbEO/5hHlsaUXv9Gq0+s+oTobin R. Sosnick41.78927490000000-87.60125000000000744Sosnick, Tobin R.Professortrue1ProfessorProfessortrue1ProfessorProfessortrue1Associate ProfessorAssociate Professortrue1ProfessorProfessortrue1Professor Professor true1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1PROFESSORPROFESSORtrue1Assistant ProfessorAssistant Professortrue1ProfessorProfessorAuthorship 6526116Authorship 6568130Authorship 667992Authorship 666762Authorship 671633Authorship 688683Authorship 673433Authorship 679769Authorship 693181Authorship 682644Authorship 703412Authorship 704282Authorship 709394Authorship 702022Authorship 703305Authorship 734271Authorship 725813Authorship 719694Authorship 713431Authorship 742474Authorship 732042Authorship 742301Authorship 740465Authorship 741703Authorship 755501Authorship 760412Authorship 750851Authorship 755111Authorship 761147Authorship 782542Authorship 777242Authorship 781456Authorship 791441Authorship 785512Authorship 784663Authorship 689323Authorship 693632Authorship 709244Authorship 728922Authorship 733131Authorship 74221212220982Sarkar IN, Thornton JW, Planet PJ, Figurski DH, Schierwater B, DeSalle RMolecular phylogenetics and evolutionAn automated phylogenetic key for classifying homeoboxes. Mol Phylogenet Evol. 2002 Sep; 24(3):388-99.Mol Phylogenet Evol2002-09-01T00:00:002002An automated phylogenetic key for classifying homeoboxes.22230956Finnigan GC, Hanson-Smith V, Stevens TH, Thornton JWNatureEvolution of increased complexity in a molecular machine. Nature. 2012 Jan 09; 481(7381):360-4.Nature2012-01-09T00:00:002012Evolution of increased complexity in a molecular machine.9819573Thornton JW, Kelley DBBioEssays : news and reviews in molecular, cellular and developmental biologyEvolution of the androgen receptor: structure-function implications. Bioessays. 1998 Oct; 20(10):860-9.Bioessays1998-10-01T00:00:001998Evolution of the androgen receptor: structure-function implications.18787702Bridgham JT, Brown JE, Rodríguez-Marí A, Catchen JM, Thornton JWPLoS geneticsEvolution of a new function by degenerative mutation in cephalochordate steroid receptors. PLoS Genet. 2008 Sep 12; 4(9):e1000191.PLoS Genet2008-09-12T00:00:002008Evolution of a new function by degenerative mutation in cephalochordate steroid receptors.18799714Carroll SM, Bridgham JT, Thornton JWMolecular biology and evolutionEvolution of hormone signaling in elasmobranchs by exploitation of promiscuous receptors. Mol Biol Evol. 2008 Dec; 25(12):2643-52.Mol Biol Evol2008-09-17T00:00:002008Evolution of hormone signaling in elasmobranchs by exploitation of promiscuous receptors.15496922Kolaczkowski B, Thornton JWNaturePerformance of maximum parsimony and likelihood phylogenetics when evolution is heterogeneous. Nature. 2004 Oct 21; 431(7011):980-4.Nature2004-10-21T00:00:002004Performance of maximum parsimony and likelihood phylogenetics when evolution is heterogeneous.12118404Thornton JW, DeSalle RSystematic biologyA new method to localize and test the significance of incongruence: detecting domain shuffling in the nuclear receptor superfamily. Syst Biol. 2000 Jun; 49(2):183-201.Syst Biol2000-06-01T00:00:002000A new method to localize and test the significance of incongruence: detecting domain shuffling in the nuclear receptor superfamily.17345582Fox JE, Bridgham JT, Bovee TF, Thornton JWYeast (Chichester, England)An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome. Yeast. 2007 May; 24(5):379-90.Yeast2007-05-01T00:00:002007An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome.12477912Thornton JW, McCally M, Houlihan JPublic health reports (Washington, D.C. : 1974)Biomonitoring of industrial pollutants: health and policy implications of the chemical body burden. Public Health Rep. 2002 Jul-Aug; 117(4):315-23.Public Health Rep2002-07-01T00:00:002002Biomonitoring of industrial pollutants: health and policy implications of the chemical body burden.19036877Keay J, Thornton JWEndocrinologyHormone-activated estrogen receptors in annelid invertebrates: implications for evolution and endocrine disruption. Endocrinology. 2009 Apr; 150(4):1731-8.Endocrinology2008-11-26T00:00:002008Hormone-activated estrogen receptors in annelid invertebrates: implications for evolution and endocrine disruption.25259920McKeown AN, Bridgham JT, Anderson DW, Murphy MN, Ortlund EA, Thornton JWCellEvolution of DNA specificity in a transcription factor family produced a new gene regulatory module. Cell. 2014 Sep 25; 159(1):58-68.Cell2014-09-25T00:00:002014Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.15707893Krylova IN, Sablin EP, Moore J, Xu RX, Waitt GM, MacKay JA, Juzumiene D, Bynum JM, Madauss K, Montana V, Lebedeva L, Suzawa M, Williams JD, Williams SP, Guy RK, Thornton JW, Fletterick RJ, Willson TM, Ingraham HACellStructural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell. 2005 Feb 11; 120(3):343-55.Cell2005-02-11T00:00:002005Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1.20837101Eick GN, Thornton JWMolecular and cellular endocrinologyEvolution of steroid receptors from an estrogen-sensitive ancestral receptor. Mol Cell Endocrinol. 2011 Mar 01; 334(1-2):31-8.Mol Cell Endocrinol2010-09-15T00:00:002010Evolution of steroid receptors from an estrogen-sensitive ancestral receptor.22528593Liberles DA, Teichmann SA, Bahar I, Bastolla U, Bloom J, Bornberg-Bauer E, Colwell LJ, de Koning AP, Dokholyan NV, Echave J, Elofsson A, Gerloff DL, Goldstein RA, Grahnen JA, Holder MT, Lakner C, Lartillot N, Lovell SC, Naylor G, Perica T, Pollock DD, Pupko T, Regan L, Roger A, Rubinstein N, Shakhnovich E, Sjölander K, Sunyaev S, Teufel AI, Thorne JL, Thornton JW, Weinreich DM, Whelan SProtein science : a publication of the Protein SocietyThe interface of protein structure, protein biophysics, and molecular evolution. Protein Sci. 2012 Jun; 21(6):769-85.Protein Sci2012-04-23T00:00:002012The interface of protein structure, protein biophysics, and molecular evolution.21209326Thornton JW, Carroll SMProceedings of the National Academy of Sciences of the United States of AmericaLamprey endocrinology is not ancestral. Proc Natl Acad Sci U S A. 2011 Jan 11; 108(2):E5; author reply E6.Proc Natl Acad Sci U S A2011-01-05T00:00:002011Lamprey endocrinology is not ancestral.20957188Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, Gauthier ME, Ortlund EA, Degnan BM, Thornton JWPLoS biologyProtein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor. PLoS Biol. 2010 Oct 05; 8(10).PLoS Biol2010-10-05T00:00:002010Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor.23864121Harms MJ, Thornton JWNature reviews. GeneticsEvolutionary biochemistry: revealing the historical and physical causes of protein properties. Nat Rev Genet. 2013 Aug; 14(8):559-71.Nat Rev Genet2013-08-01T00:00:002013Evolutionary biochemistry: revealing the historical and physical causes of protein properties.17702911Ortlund EA, Bridgham JT, Redinbo MR, Thornton JWScience (New York, N.Y.)Crystal structure of an ancient protein: evolution by conformational epistasis. Science. 2007 Sep 14; 317(5844):1544-8.Science2007-08-16T00:00:002007Crystal structure of an ancient protein: evolution by conformational epistasis.23798447Harms MJ, Eick GN, Goswami D, Colucci JK, Griffin PR, Ortlund EA, Thornton JWProceedings of the National Academy of Sciences of the United States of AmericaBiophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors. Proc Natl Acad Sci U S A. 2013 Jul 09; 110(28):11475-80.Proc Natl Acad Sci U S A2013-06-24T00:00:002013Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors.15922825Thornton JW, Kolaczkowski BTrends in genetics : TIGNo magic pill for phylogenetic error. Trends Genet. 2005 Jun; 21(6):310-1.Trends Genet2005-06-01T00:00:002005No magic pill for phylogenetic error.25386647Hart KM, Harms MJ, Schmidt BH, Elya C, Thornton JW, Marqusee SPLoS biologyThermodynamic system drift in protein evolution. PLoS Biol. 2014 Nov; 12(11):e1001994.PLoS Biol2014-11-11T00:00:002014Thermodynamic system drift in protein evolution.17703238Dean AM, Thornton JWNature reviews. GeneticsMechanistic approaches to the study of evolution: the functional synthesis. Nat Rev Genet. 2007 Sep; 8(9):675-88.Nat Rev Genet2007-09-01T00:00:002007Mechanistic approaches to the study of evolution: the functional synthesis.12899845Wu KH, Tobias ML, Thornton JW, Kelley DBGeneral and comparative endocrinologyEstrogen receptors in Xenopus: duplicate genes, splice variants, and tissue-specific expression. Gen Comp Endocrinol. 2003 Aug; 133(1):38-49.Gen Comp Endocrinol2003-08-01T00:00:002003Estrogen receptors in Xenopus: duplicate genes, splice variants, and tissue-specific expression.19779450Bridgham JT, Ortlund EA, Thornton JWNatureAn epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature. 2009 Sep 24; 461(7263):515-9.Nature2009-09-24T00:00:002009An epistatic ratchet constrains the direction of glucocorticoid receptor evolution.24415950Bridgham JT, Keay J, Ortlund EA, Thornton JWPLoS geneticsVestigialization of an allosteric switch: genetic and structural mechanisms for the evolution of constitutive activity in a steroid hormone receptor. PLoS Genet. 2014 Jan; 10(1):e1004058.PLoS Genet2014-01-09T00:00:002014Vestigialization of an allosteric switch: genetic and structural mechanisms for the evolution of constitutive activity in a steroid hormone receptor.18319244Kolaczkowski B, Thornton JWMolecular biology and evolutionA mixed branch length model of heterotachy improves phylogenetic accuracy. Mol Biol Evol. 2008 Jun; 25(6):1054-66.Mol Biol Evol2008-03-03T00:00:002008A mixed branch length model of heterotachy improves phylogenetic accuracy.20011052Kolaczkowski B, Thornton JWPloS oneLong-branch attraction bias and inconsistency in Bayesian phylogenetics. PLoS One. 2009 Dec 09; 4(12):e7891.PLoS One2009-12-09T00:00:002009Long-branch attraction bias and inconsistency in Bayesian phylogenetics.11331759Thornton JWProceedings of the National Academy of Sciences of the United States of AmericaEvolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc Natl Acad Sci U S A. 2001 May 08; 98(10):5671-6.Proc Natl Acad Sci U S A2001-05-01T00:00:002001Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions.11701624Thornton JW, DeSalle RAnnual review of genomics and human geneticsGene family evolution and homology: genomics meets phylogenetics. Annu Rev Genomics Hum Genet. 2000; 1:41-73.Annu Rev Genomics Hum Genet2000-01-01T00:00:002000Gene family evolution and homology: genomics meets phylogenetics.24930765Harms MJ, Thornton JWNatureHistorical contingency and its biophysical basis in glucocorticoid receptor evolution. Nature. 2014 Aug 14; 512(7513):203-7.Nature2014-06-15T00:00:002014Historical contingency and its biophysical basis in glucocorticoid receptor evolution.21698144Carroll SM, Ortlund EA, Thornton JWPLoS geneticsMechanisms for the evolution of a derived function in the ancestral glucocorticoid receptor. PLoS Genet. 2011 Jun; 7(6):e1002117.PLoS Genet2011-06-16T00:00:002011Mechanisms for the evolution of a derived function in the ancestral glucocorticoid receptor.16601189Bridgham JT, Carroll SM, Thornton JWScience (New York, N.Y.)Evolution of hormone-receptor complexity by molecular exploitation. Science. 2006 Apr 07; 312(5770):97-101.Science2006-04-07T00:00:002006Evolution of hormone-receptor complexity by molecular exploitation.16837562Kolaczkowski B, Thornton JWMolecular biology and evolutionIs there a star tree paradox? Mol Biol Evol. 2006 Oct; 23(10):1819-23.Mol Biol Evol2006-07-12T00:00:002006Is there a star tree paradox?15143319Thornton JWNature reviews. GeneticsResurrecting ancient genes: experimental analysis of extinct molecules. Nat Rev Genet. 2004 May; 5(5):366-75.Nat Rev Genet2004-05-01T00:00:002004Resurrecting ancient genes: experimental analysis of extinct molecules.20413295Harms MJ, Thornton JWCurrent opinion in structural biologyAnalyzing protein structure and function using ancestral gene reconstruction. Curr Opin Struct Biol. 2010 Jun; 20(3):360-6.Curr Opin Struct Biol2010-04-21T00:00:002010Analyzing protein structure and function using ancestral gene reconstruction.23166518Eick GN, Colucci JK, Harms MJ, Ortlund EA, Thornton JWPLoS geneticsEvolution of minimal specificity and promiscuity in steroid hormone receptors. PLoS Genet. 2012; 8(11):e1003072.PLoS Genet2012-11-15T00:00:002012Evolution of minimal specificity and promiscuity in steroid hormone receptors.16690796Keay J, Bridgham JT, Thornton JWEndocrinologyThe Octopus vulgaris estrogen receptor is a constitutive transcriptional activator: evolutionary and functional implications. Endocrinology. 2006 Aug; 147(8):3861-9.Endocrinology2006-05-11T00:00:002006The Octopus vulgaris estrogen receptor is a constitutive transcriptional activator: evolutionary and functional implications.20368266Hanson-Smith V, Kolaczkowski B, Thornton JWMolecular biology and evolutionRobustness of ancestral sequence reconstruction to phylogenetic uncertainty. Mol Biol Evol. 2010 Sep; 27(9):1988-99.Mol Biol Evol2010-04-05T00:00:002010Robustness of ancestral sequence reconstruction to phylogenetic uncertainty.17636043Kolaczkowski B, Thornton JWMolecular biology and evolutionEffects of branch length uncertainty on Bayesian posterior probabilities for phylogenetic hypotheses. Mol Biol Evol. 2007 Sep; 24(9):2108-18.Mol Biol Evol2007-07-17T00:00:002007Effects of branch length uncertainty on Bayesian posterior probabilities for phylogenetic hypotheses.11005855Hawkins MB, Thornton JW, Crews D, Skipper JK, Dotte A, Thomas PProceedings of the National Academy of Sciences of the United States of AmericaIdentification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts. Proc Natl Acad Sci U S A. 2000 Sep 26; 97(20):10751-6.Proc Natl Acad Sci U S A2000-09-26T00:00:002000Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts.14500980Thornton JW, Need E, Crews DScience (New York, N.Y.)Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling. Science. 2003 Sep 19; 301(5640):1714-7.Science2003-09-19T00:00:002003Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling.Authorship 80914326076233Anderson DW, McKeown AN, Thornton JWeLifeIntermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites. Elife. 2015 Jun 15; 4:e07864.Elife2015-06-15T00:00:002015Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites.Chicago60637ILAuthorship 85357826740169Anderson DP, Whitney DS, Hanson-Smith V, Woznica A, Campodonico-Burnett W, Volkman BF, King N, Thornton JW, Prehoda KEeLifeEvolution of an ancient protein function involved in organized multicellularity in animals. Elife. 2016 Jan 07; 5:e10147.Elife2016-01-07T00:00:002016Evolution of an ancient protein function involved in organized multicellularity in animals.Authorship 91093226833806Starr TN, Thornton JWProtein science : a publication of the Protein SocietyEpistasis in protein evolution. Protein Sci. 2016 07; 25(7):1204-18.Protein Sci2016-02-28T00:00:002016Epistasis in protein evolution.Authorship 96394527795231Eick GN, Bridgham JT, Anderson DP, Harms MJ, Thornton JWMolecular biology and evolutionRobustness of Reconstructed Ancestral Protein Functions to Statistical Uncertainty. Mol Biol Evol. 2017 02 01; 34(2):247-261.Mol Biol Evol2017-02-01T00:00:002017Robustness of Reconstructed Ancestral Protein Functions to Statistical Uncertainty.Authorship 99670228178247Starr TN, Thornton JWNature biotechnologyExploring protein sequence-function landscapes. Nat Biotechnol. 2017 02 08; 35(2):125-126.Nat Biotechnol2017-02-08T00:00:002017Exploring protein sequence-function landscapes.