TheoryinBiosciences124(2006)349 - PDF document

TheoryinBiosciences124(2006)349…369TheproperplaceofhopefulmonstersinevolutionarybiologynterTheißenJena,LehrstuhlfuGenetik,Philosophenweg12,D-07743Jena,GermanyReceived9October2005;accepted13November2005Hopefulmonstersareorganismswithaprofoundmutantphenotypethathavethepotentialtoestablishanewevolutionarylineage.TheSyntheticTheoryofevolutionarybiologyhasrejectedtheevolutionaryrelevanceofhopefulmonsters,butcouldnotfullyexplainthemechanismandmodeofmacroevolution.Ontheotherhand,severallinesofevidencesuggestthathopefulmonstersplayedanimportantroleduringtheoriginofkeyinnovationsandnovelbodyplansbysaltationalratherthangradualevolution.Homeoticmutantsareidenti“edasan Tel.:+493641949550;fax:+493641949552.E-mailaddress:guenter.theissen@uni-jena.de. Introduction:navigatingevolutionarybiologythroughtheSkyllaofgradualismandtheCharybdisofintelligentdesignOurplanetisinhabitedbyanimpressivenumberofincrediblycomplexanddiverseorganisms,suchasplantsandanimals(includinghumanbeings).Comparedtothecomplexityof,say,thehumanbody,eventheSpaceShuttlelooksquitepoor,andthediversityofinsectsaloneisjustbreathtaking.Explainingexactlyhowthegreatcomplexityanddiversityoflifeonearthoriginatedisstillanenormousscienti“cchallenge(Carroll,2001).Itmay“rstappearunnecessarytopointoutthatthescienti“cmethodhastobebroughttobearontheproblem.Inadditiontotheinherentbiologicalcomplexityoftheproblem,however,Icurrentlyseetwoothermajorobstaclesforfutureprogressfromaheuristicperspectivethatmayjustifysucharemark:(i)Thereisthewidespreadattitudeinthescienti“ccommunitythat,despitesomeproblemsindetail,textbookaccountsonevolutionhaveessentiallysolvedtheproblemalready.Inmyview,thisisnotquitecorrect.(ii)Thereistheoppositeviewgaininggroundmainlyoutsideofscienti“ccirclesthatlivingorganismsaresocomplexthattheymusthavebeencreatedbyanexternalintelligence…anovelversionofcreationismknownasIntelligentDesign(ID).AphilosophicalanalysisofwhetherIDisascienti“chypothesisatallisbeyondthescopeofthisreview.Inanycase,itsabilitytodevelopfruitfulresearchprogramshasremainednegligiblesofar(Raff,2005).Withfewexceptions(e.g.,nnig,2004,andreferencescitedtherein)biologistsdonotconsiderIDhelpfulinourendeavourtoexplainlifescomplexityanddiversity.Thisdoesnotmean,however,thatwealreadyhaveacompleteandsatisfactorytheorywhichexplainshowthecomplexityanddiversityoflifeoriginated.ThustherejectionofIDorothervarietiesofcreationismisnotbasedonthecomprehensiveexplanatorypowerofanyexistingevolutionarytheory,buthastobeconsideredasanepistemologicalpresuppositionandheuristicbasisofbiologyasanaturalscience.Sincewedonothaveacompleteaccountoftheoriginofcomplexorganismalfeatures,clarifyingtheiroriginarguablyremainsoneofthegreatestchallengesofbiology(Lenskietal.,2003Allwell-supportedscienti“ctheoriesusedtoexplainthecomplexityanddiversityoflivingbeingsarevariantsofevolutionaryhypotheses.Accordingto,evolutionisatwo-stageprocess:heritablerandomvariationprovidestherawmaterial,naturalselectionactsasthedirectingforcethatleadstotheadaptationoforganismstotheenvironment.Byunitingtheclassicalobservationsofmorphology,systematics,biogeographyandembryologywithpopulationgeneticstheSyntheticTheory(orModernSynthesis)ofevolutionarybiologywasdevelopedduringthe1930sand1940s(Dobzhansky,1937Mayr,1942Simpson,1944MayrandProvine,Reifetal.,2000JunkerandHoßfeld,2001Junker,2004).TheSyntheticTheoryconsidersevolutionusuallyastheresultofchangesinallelefrequencyduetoARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 naturalselectionthatengendersubtlemodi“cationsofphenotype.LikeDarwintheSyntheticTheoryarguesthatevolutionoccursalwaysgradually,andthatcomplexanduniquestructuresevolvethroughanalmostin“nitenumberofgenerationssubjecttonaturalselection“ne-tuningthesetraits.Intime,suchgradualchangesaccumulateandresultinlargedifferencesuniquetohighertaxa.Gradualism,thatevolutionproceedsbyverysmallstepsandthiswaycreatestheuniquetraitsatalllevelsofbiologicaldiversity,canbeseenasacentraltenetofDarwinandtheSyntheticTheory.Accordingtothisview,thegradualprocessofevolutionbynaturalselectionthatoperateswithinpopulationsandspecies(oftentermedmicroevolution)alsocreatestheuniquetraitsrecognizableathighertaxonomiclevels(oftentermedmacroevolution).Macroevolutionisusuallyde“nedasevolutionatandabovethespecieslevel.Speciation,however,cangoalongwithalmostnostructuralandfunctionalchanges,whileevenwithinspecies,therecanbedramaticmorphologicaldifferences(e.g.,maizevs.teosinte,seebelow).InthefollowingIwillusethetermmacroevolutioninamorenarrowsenseonlyforthoseevolutionaryprocessesthatbringaboutinnovations(ornovelties),orchangesinbodyplans.EveninthisterminologytheSyntheticTheorymaintainsthatmacroevolutionisjustmicroevolutionextendedoverlargeperiodsoftime.Despiteallitsindisputableexplanatorypower,theSyntheticTheoryhasseriousshortcomings(Wagner,2000).Theempiricalbasisofgradualismisweakatbest.Themostdirectviewintolifespastonearthisprovidedbythefossilrecord.Withitsabrupttransitions,however,itprovideslittleevidenceforagradualevolutionofnewforms(GouldandEldredge,1993).Alsothebranchingpatternsofhighertaxainbothanimalsandplantsasrevealedbycladisticsandsystematicsdonotsupporttheideathatthemajorfeaturesofbodyplansandtheirconstituentpartsaroseinagradualway(Vergara-Silva,2003).Moreover,eventhoughpopulationgeneticsmightbethemostelaborateapproachthatwehavetoexplainevolution,itmightnotbesuf“cient.Forexample,itfallsshortofexplaininginnovationsandconstraints,andtheevolutionofbodyplans(Riedl,1977Gilbertetal.,1996Wagner,2000HaagandTrue,2001WagnerandMuller,2002WagnerandLaubichler,2004Whydidbacterianotjustgiverisetomoreandmoreoptimizedandbetterandbetteradaptedbacteriaforever,buttomushrooms,monkey”owersandman?Infact,populationgeneticstellsuslittleaboutthemechanismsbywhichchangesinalinearsequenceofnucleotidesthatconstitutesthegenomesoflivingorganismsproducesthediversityandcomplexityoflife(Weiss,2005).Changesinallelefrequencywithinpopulationsarecertainlyofgreatimportanceforunderstandingevolutionandtheoriginofbiodiversity,buttheyarebyfarnotsuf“cient,becausethenumberofgeneticlociisnot“xedinevolution(e.g.,animalsandplantshaveroughlyabout10timesmoregenesthanbacteria).Newgenesoriginateduringevolutionbyprocessessuchasgene,chromosomeorwholegenomeduplications,andgenescanlosetheirfunctionandevengetlost,e.g.bydeleteriousmutations.Thebirthanddeathofgenesaswellaschangesinregulatoryorgeneticinteractionsbetweenexistinggenesareofspecialimportanceduringtheevolutionaryoriginofkeyinnovationsandnovelties(Theißen,2002,2005ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369351 Inadditiontoexplanatoryde“citstheSyntheticTheoryalsohasphilosophicalshortcomings.Bymaintainingthatevolutionmustbegradualandthatmacroevolu-tionarypatternscanbefullyexplainedbytheactionofnaturalselectionandadaptationtotheenvironmentalone,theSyntheticTheorymadeover-extendedclaims,andhencelefttherealmofscienceanddevelopedintoanideology(andLaubichler,2004).Weshouldnotforget,however,thatallscienti“cknowledgeishypotheticalandpreliminary,andthatthereisnoreasonwhythisshouldnotalsoapplytoscienti“cexplanationsofthecomplexityanddiversityoflife.Thatallformsoflifeoriginatedinagradualway,therefore,mightbeconsideredanextremelyinterestinghypothesis,butinthenaturalsciencesthereisnosuchthingasaprovenSoinitsquesttoexplaintheoriginofcomplexorganismsonourplanet,evolutionarybiologyshouldrememberitsbasicprinciples.Withinthisframeworkitshould,however,alsobemoretoleranttowardsalternativeviews.Thevastmajorityofbiologistswillagreethatevolutionisinevitablewhenafewconditionsaremet:replication,variation(mutation),anddifferential“tness(competition)(Dennett,).Butwhiletheseprinciplesmighteasilyexplainhowanykindoforganismgivesrisetoanoptimizedorganism(concerningwhatevercriteria),itishardtoseehowitexplainstheoriginofe.g.eukaryotes,plantsandanimalsfromprokaroytes.Studiesofdigitalorganismssuggestthatcomplexfunctionscanoriginatebyrandommutationandnaturalselection(Lenskietal.,2003),buttheextenttowhichsuchinsilicostudiesre”ectevolutionaryeventsinlivingorganismsremainsunclear.Insightsintothedevelopmentalgeneticsofmulticellularorganismsaswellasthefossilrecordsuggestthatevolutioncanbesaltationalratherthangradual.Formanyyears,however,thetraditionalpopulation-genetictenetsoftheSyntheticTheorymadeimpossibleaseriousdiscussionofsaltationalmechanismsasexplanationsofmacroevolutionarychange(Vergara-Silva,2003).ButgiventheproblemstheSyntheticTheoryfacesinexplainingthemodesandmechanismsofmacroevolutionbiologyshouldalsoconsideralternativemechanisms,aslongastheyareaccessiblebyscienti“cmethods.HereIarguethatsaltationalevolutionoccurred,andthathopefulmonstersmighthaveactedas“rststepsinthisprocess.Ibrie”yreviewtheshortbutcontroversialhistoryoftheconceptofhopefulmonsters,andoutlinethat,ifitistobeausefuladditiontoevolutionarybiology,itneedsbothconceptualre“nementsandempiricaltests.Hopefulmonsters:GoldschmidtslegacyThetermhopefulmonsterwasintroducedbyRichardGoldschmidtdecadesago.Goldschmidtsawtruespeciesseparatedbybridgelessgapsthatcouldonlybeovercomebysaltationalchanges,andnotbytheslowgradualchangesenvisagedbyDarwinandtheSyntheticTheory.Inordertoexplaintheoriginofspecies,therefore,Goldschmidt(1940)developedviewsthatbrokesharplywiththeSyntheticTheoryARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 (reviewedbyDietrich,2000,2003).Whileheraisednoobjectiontogradualandcontinuouschangewithinspecies,hearguedthatnewspeciesariseabruptlybydiscontinuousvariation,ormacromutation.Goldschmidtwasawarethatthevastmajorityofmacromutationshavedisastrouseffectsonthe“tnessoforganisms…thesehecalledmonsters.ButinGoldschmidtsvieweveryonceinawhileahopefulmonsterisgeneratedwhichisadaptedtoanewmodeoflife.AccordingtoGoldschmidt,macroevolutionproceedsbytheraresuccessofthesehopefulmonstersratherthanbyanaccumulationofsmallchangeswithinpopulations.Goldschmidt(1940)presentedtwomechanismsforhowhopefulmonstersmightoriginate.The“rstoneisbasedondevelopmentalmacromutationsinrategenesorcontrollinggenesthatchangeearlydevelopmentandhencecauselargeeffectsintheadultphenotype.Whilethesekindsofmutationswerebasedontheclassicalgeneconcept,Goldschmidtrejectedtheclassicalmodelofthegeneinthesecondmechanism,anddevelopedanalternativemodelinwhichsystemicrearrangementsofchromosomes(systemicmutations)couldproducenewdevelopmentalsystemsandpotentiallynewspeciesquickly.Goldschmidtsideaofhopefulmonsterswasnottiedtohisideaofsystemicmutations,butheusedthepossibilityofmutationsindevelopmentallyimportantgenestomakethegeneticmechanismofsystemicmutationmoreplausible.AccordingtoDietrich(2003)itwashisrejectionoftheclassicalgeneconceptevenmorethanhisviewsonsaltationalevolutionviahopefulmonstersthatdamagedGoldschmidtsscienti“creputationand,tosomeextent,alsothecredibilityofhopefulmonsters.Hopelessmonsters:theSyntheticTheorystrikesbackGoldschmidtsideasaboutdevelopmentallyimportantmutantswithlargeeffectswerenotmetwiththesamehostilityashisviewsonsystemicmutations(Dietrich,).However,hedidnotsucceedinestablishinghopefulmonstersasanacceptedadditiontoevolutionarytheory.RepresentativesoftheSyntheticTheorysawtheaccumulatingevidenceoftheevolutionaryimportanceofselectiononmanymutationsofsmalleffectanddifferentiationatthepopulationlevelasindicationthatthereisnoneedforhopefulmonstersinevolutionarybiology(Dietrich,2003Simpson(1944)homeoticmutantswereinsuf“cienttoexplainthedistinctionbetweenmicroevolutionandmacroevolution.Wright(1941)Simpson(1944)raisedanumberofobjectionstoGoldschmidtsviewsabouttheevolutionaryimportanceofdrasticmutants,e.g.that,likeanyothermutant,theydonotcreatenewspecies,andthattheappearanceofamutantindividualisnotevolution.Towhom,forexample,shallhopefulmonstersmate?Allitsrelativesareverydifferentfromit,arguablyevenmembersofanotherspecies.Andthechancethatorganismswithreasonable“tnessweregeneratedratherthanhopelessmonsterswasconsideredtobeverylow.Insimplemodelsthe“tnessofanorganismdecreasesproportionallytoitsdeviationfromthewildtype.Itcanthusbeassumedthatprofoundphenotypictransformationsunderminethe“tnessoftheaffectedARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369353 organismsinsuchaseriouswaythatthereisalwaysstrongselectionagainstthem(reviewedbySvensson,2004).Thusfromapopulationgeneticspointofview,hopefulmonstersappearedimpossible.NotlongafterRichardGoldschmidtsbrainchildhadenteredtheworldofideasinevolutionarybiology,therefore,hopefulmonstersweregenerallyconsideredahopelesscase.Itisstillwidelybelievedthatanymutationofmajoreffectisunlikelytobetoleratedbynaturalselectionandthusgenerateshopelessratherthanhopefulmonsters(Akam,1998Helpfulmonsters:homeoticmutantsentertheevo-devostageHopefulmonstersremainedanathemaaslongastheoreticalpopulationgeneticmodelsdominatedevolutionarybiologyanddevelopmentalbiologyremainedaneglectedtopic.Thesituationchanged,however,mainlyduetoquantitativetraitloci(QTL)analysesofrealdifferencesbetweencloselyrelatedorganisms,andtheongoingreintegrationofdevelopmentalbiologyintoevolutionarybiology.InrecentyearsQTLanalysesrevealedthatnovelmorphologicalformsinevolutionmayresultfromchangesinjustafewgenesoflargeeffect.Themostintenselystudiedcaseinplantsisthedomesticationofmaize(Zeamays.ssp.fromteosinte(Zeamaysparviglumis).Duringthisprocessthefemalein”orescence(ear)ofcornoriginatedasanunprecedentednoveltyduetochangesatjustabout“vegeneloci(Doebleyetal.,1997Wangetal.,1999Wangetal.,).Ithasbeenarguedthattheselectionregimeduringdomesticationisverydifferentfromthatofevolutioninthewild.ButQTLanalysesofnaturallyoccurringpolymorphismsaffecting”owerandin”orescencestructurescorroboratedtheviewthatevendrasticstructuralchangescanbebasedonmutationsatjustoneorafewgeneticloci(see,e.g.,GailingandBachmann,2000MoritzandKadereit,2001Majorde“cienciesintheSyntheticTheory,e.g.inexplainingevolutionarynoveltiesandconstraints,ledtothereintegrationofdevelopmentalbiologyintoevolutionarybiology,givingrisetoevolutionarydevelopmentalbiology(evo-devo,forshort).Theevo-devorationaletakesintoconsiderationthatmulticellularorganismsusuallydevelopfromsinglecells(zygotes)ineachgenerationanew.Thisimpliesthatmorphologicalchangesinevolutionoccurbychangesindevelopmentalprocesses.Sincedevelopmentislargelyundergeneticcontrol,novelmorpholo-gicalformsinevolutionfrequentlyresultfromchangesindevelopmentalcontrolgenes.Thusevo-devoprojectsoftenstudythephylogenyofdevelopmentalcontrolgenesandtheirroleintheevolutionofmorphologicalfeatures(fordetailsoftheevo-devorationale,seeGould,1977bGilbertetal.,1996Theißenetal.,2000Carroll,Arthur,2002Inrecentyearsmuchprogresshasbeenmadeinunderstandingthegeneticmechanismsthatbringaboutdrasticyetcoordinatechangesintheadultphenotypebymodi“cationofdevelopment.Changesinboththetiming(heterochrony)andtheposition(heterotopy)ofdevelopmentalprocessescanoccur.Inthecaseofplants,however,heterotopyandheterochronyareoftendif“culttodistinguish,becauseARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 plantsdevelopcontinuously,soshiftingdevelopmentaleventslaterorearlierduringplantlifemayleaddirectlytoachangeinthepositionofthestructuregeneratedbythedevelopmentalprogram(Kellogg,2000).Quiteanumberofevolutionarynoveltiesandcharacteristicsofmajorclades…manyofwhichhavebeenusedfordecadesastaxonomiccharacters„canbeexplainedastheresultofheterotopyorheterochrony,underscoringitsimportanceformacroevolution(Kellogg,2000Animportantsubsetofheterotopicchangesarehomeotictransitions(BaumandDonoghue,2002).ThetermhomeosishadbeencoinedbyWilliamBatesonin1894todescribeatypeofvariationinwhichsomethinghasbeenchangedintothelikenessofsomethingelse(Lewis,1994).Well-knownexamplesareprovidedbythefruit”yDrosophilamelanogaster,suchastheAntennapediamutant,whichhasantennaereplacedbyleg-likeorgans,ortwomutantsstudiedbyRichardGoldschmidt,podoptera,withtransformationofwingsintoleg-likestructures,andtetraltera,withtransformationofwingsintohalteres(reviewedbyDietrich,2000Homeoticmutantsarealsofrequentinplants,affectingbothvegetativeandreproductiveorgans(Sattler,1988Meyerowitzetal.,1989).Especiallywellknownare”oralhomeoticmutants,i.e.mutantplantswith”owersthathavemoreorlessnormal”oralorgansinplaceswhereorgansofanothertypearetypicallyfound.Many”owersconsistoffourdifferenttypesoforganswhicharearrangedinfourwhorls:sepals,petals,stamensandcarpels.InthemodelplantthalecressArabidopsisthaliana)homeoticmutantscanbecategorizedintothreeclasses:A,BandC.IdealclassAmutantshavecarpelsinthe“rstwhorlinsteadofsepals,andstamensinthesecondwhorlinsteadofpetals.ClassBmutantshavesepalsratherthanpetalsinthesecondandcarpelsratherthanstamensinthethirdwhorl.AndclassCmutantshave”owersinwhichreproductiveorgans(stamensandcarpels)arereplacedbyperianthorgans(petalsandsepals,respectively),andinwhichthedeterminacyof”oralgrowthislost,resultinginanincreasednumberof”oralorgansMeyerowitzetal.,1989Theißen,2001).Such“lled”owersarewellknownfrommanywildandornamentalplants,includingArabidopsisAntirrhinum(rose),(e.g.,cherry),Petunia(tulip)(Fig.1BThede“nedclassesofhomeoticmutantsareexplainedbysimplecombinatorialmodelssuchastheABCmodelof”owerdevelopment(reviewedbyTheißen,2001Itproposesthreedifferent”oralhomeoticfunctionstoexplainhowthedifferent”oralorgansadopttheiruniqueidentitiesduringdevelopment.ThesefunctionsaretermedA,BandC,withAspecifyingsepalsinthe“rst”oralwhorl,A+Bpetalsinthesecondwhorl,B+CstamensinthethirdwhorlandCcarpelsinthefourthwhorl.Cloningofhomeoticgenesduringthe1980sand1990sinbothanimalsandplantsrevealedthattheyallencodetranscriptionfactors,i.e.proteinsthatrecognizespeci“cDNAmotifsofothergenesandin”uencetheirtranscription.Whilethehomeoticgenesofanimalsencodehomeodomainproteins,thevastmajorityofhomeoticgenesofplantsencodeMADS-domainproteins(Gehring,1992Carroll,1995BeckerandTheißen,2003Theißen,2001Meyerowitz,2002Homeoticgenesrevealthatmajordevelopmentaleventssuchasthespeci“cationoforganidentityareoftenunderthecontrolofalimitednumberofdevelopmentalcontrolgenes.TheanalysesofmutantsandtransgenicorganismsdemonstratethatARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369355 ARTICLEINPRESS Fig.1.Aputativehopeless(B)andhopefulmonster(D).Intheupperrow,awild-type”oweroftulip(Tulipagesneriana,left)iscomparedtoadouble”oweror“lled”owermutant(right);whilethewild-type”owerhasmale(stamens)andfemalereproductiveorgans(carpels)inthecentre,the“lled”owerissterile,becauseallreproductiveorgansaretransformedintoshowyyetsterileperianthorgans,thushamperingsexualreproductionandundermining“tness.Thelowerpartshowsin”orescencesofShepherdspurse(Capsellabursa-pastorisWhilewild-type”owershavefourdifferenttypesof”oralorgansincludingpetals(thewhiteorgansinC),allpetalsaretransformedintostamensinthedecandricvarietyshowninD,whichhencehas10stamensand2carpelsinallofits”owersandisfullyfertile.Notethatwhileevolutionarybiologyusuallyfavoursanimalmodelsystems(anattitudeknownaszoocentrism),theinsectsshownhereareonlydecorativeelements.(PicturescourtesyofHanneloreSimon(upperrow)andJanineZiermann(lowerrow)).G.Theißen/TheoryinBiosciences124(2006)349…369 changesintheselocicanbringaboutprofound,yetcoordinatedmorphologicalchanges.Someofthemutantphenotypes(e.g.,petaloidratherthansepaloid1stwhorl”oralorgans,actinomorphicratherthanzygomorphic”owers,four-wingedratherthantwo-winged”ies),resembledifferencesincharacterstatesbetweenmajororganismiclineages.Thereisalongdebategoingonastowhetherthegenesunderlyingsuchphylomimickingmutants(HaagandTrue,2001)de“nelocithatplayanimportantroleincharacterchangesduringmacroevolution.Asamatteroffact,changesintheexpressiondomainsof”oralhomeoticgenesinmutantortransgenicplantscanbringabouthomeotictransformationsof”oralorgans.Forexample,theexpressionofclassCgenesinthewhorlsoftheperianthleadstoatransformationofsepalsintocarpelloidorgansandofpetalsintostaminoidorgans(Bradleyetal.,1993).Similarly,theectopicexpressionofclassBgenesinthe1stand4th”oralwhorlsofArabidopsisleadstoatransformationofsepalsintopetaloidorgansandofcarpelsintostaminoidorgans(KrizekandMeyerowitz,1996).Asurveyduringthecourseofevo-devoprojectssuggestedthatthesechangesdonotonlyunderlieshort-livedtransgenicandmutantplants,butalsonaturalmorphologicaldiversitygeneratedduringmacroevolution,andthusaresuitablemodelsforevolutionaryprocesses.Forexample,tulips(Tulipagesnerianaandotherlilylikeplants(Liliaceae)have”owersdisplayingorganidentitiesquitesimilartotheonesofhighereudicots,but“rstwhorlorgansaretypicallypetaloidlikesecondwhorlorgansratherthansepaloid(Fig.1A).Thissuggeststhatahomeotictransitioninthe“rst”oralwhorlfromsepaloidtopetaloidorganidentity,orviceversa,occurredduringtheevolutionof”oweringplants.PetaloidorganidentityrequiresthefunctionofclassB”oralhomeoticgenes.Indeed,whenclassBgeneswereinvestigatedintulip,theywerefoundtobeexpressednotonlyinthepetaloidtepalsofthesecond”oralwhorl,butalsointheorgansofsimilaridentityinthe“rstwhorl(Kannoetal.,2003).Similarexamplesareprovidedbymany”owersofthebasaleudicotfamilyRanunculaceae,whichhavedistinctlydifferentpetaloidorgansinthe“rsttwowhorls.Expressionstudiessuggestedthatpetaloidyof1stwhorlorgansisduetoashiftofclassBgeneexpressiontowardsthe1st”oralwhorlKrameretal.,2003These“ndingssupporttheviewthatshiftsintheboundariesofclassB”oralhomeoticgeneexpressionthatbroughtabout”oralhomeoticchangescontributedtothediversityof”oralarchitecture.Theyaddtoagrowingstreamofreasoningfuelledbyevolutionaryanalysesofmorphologicalcharacters,allindicatingthathomeosisplayedasigni“cantroleinplantevolution.Forexample,Sattler(1988)putativecasesofhomeosisintheevolutionof”oweringplantsfromthecellulartotheorganismiclevel,includingseveralaffectingvegetativeorganssuchasleavesandlea”ets.Theoriginofmaizefromteosintewithitsdramaticchangesthatgaverisetothefemalein”orescence(ear)ofmaizehastraditionallyinvitedscientiststoexplainitinvolvingdramatic,evencatastrophiceventssuchashomeosis(1983,2000Kellogg(2000)summarizedevidencefortheimportanceofheterotopyduringtheevolutionofgrasses(Poaceae);examplesincludetheevolutionoftheuniqueepidermalmorphologyofgrasses,theoriginofthegrass”owerandspikelet,theformationofunisexual”owersinthepanicoidgrassesandtherepeatedoriginofARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369357 C4photosynthesis.Incontrast,heterochronymayunderliethenovelmorphologyofthegrassembryo(Kellogg,2000RonseDeCraene(2003)providedmorphologicalevidencefortheevolutionarysigni“canceofhomeosisinthe”owersofdiverseangiosperms,suchasRosaceae,PapaveraceaeandLacandonia.Forexample,thereisstrongphylogeneticandmorphologicalevidencethatthepetalsoftheRosaceae(comprisingwell-knowncultivatedplantssuchasroses,strawberriesandapples)werederivedfromstamens(RonseDeCraene,2003BaumandDonoghue(2002)reconsideredtheconceptoftransferenceoffunctionduringplantevolution,includingmanyputativecasesofhomeosis.ModelsofhowevolutionaryvariationoftheABCsystemof”oralorganidentityspeci“cationcouldexplain”oraldiversi“cationduringevolutionhavebeenprovidede.g.byTheißenetal.(2000)Krameretal.(2003)RudallandBateman(2002,2003)describeddifferentkindsofteratologicalplantswithpeloric”owers,especiallyinorchidsandthemintfamily,whichcanbeunderstoodintermsofheterotopyandhomeosis.RutishauserandIslerRutishauserandMoline(2005)consideredhomeosisorevenmoreradicalconceptssuchasfuzzymorphologyandcontinuummorphologytoexplainatleastsomeoftheextremepeculiaritiesinthebodyplansofbladderwortsUtricularia)andriver-weeds(Podostemaceae),respectively.Itismaybenotbychancethatalltheseexamplesrepresentplants.Itcouldwellbethatthemoreopenstructureandadditivemodeofgrowthofplantsimpliesthathomeoticmutationsaremoreimportantinplantthaninanimalevolution.However,evidenceforhomeoticshiftsinanimalevolutionisnotcompletelylacking.Aninstructiveexampleisthedigitsinthebirdhand,whichwasinferredbycon”ictsinhomologyassignments.Traditionalcriteriaforrecognizinghomologousfeaturesincludestructuralsimilarity,positionwithinacomparablesetoffeatures,andtheexistenceoftransitionalformsbetweenpresumptivehomologues,eitherindevelopment(ontogeny)orevolution(asrevealedbythefossilrecord)(RutishauserandIsler,2001Theißen,2005;andreferencestherein).Theappendagesofmanytetrapodshave5digits,whilebirdwingshavejust3.Thedigitsofthewingsofbirdsareconsideredonembryologicalgroundstobedigits2,3,and4,whilephylogeneticanalysesoffossildataindicatethatbirdsdescendedfromtheropoddinosaursthathadlostdigits4and5andthushavedigits1,2,3.ButhowcanitbethatWagnerandGauthier(1999)suggestedthatahomeotictransforma-tionoccurred,sothatnowe.g.adigitdevelopingatposition2hastheorganidentity(orspecialquality)ofanposition1organ(hence21).ExpressionstudiesofHoxgenesdeterminingdigitidentityarecompatiblewiththishypothesis,althoughalternativeexplanationsremainconceivable(VargasandFallon,2005).Thehandsofkiwisandtyrannosaurscouldrepresentfurthercasesofnaturalhomeotictransformationofdigits(WagnerandGauthier,1999Takentogether,thereisincreasingevidence,mainlyfromplants,butalsofromanimals,thathomeotictransitionshaveindeedoccurredduringevolution,andthatthesearebasedonmutationsinjustoneorafewgeneticloci.Inprinciple,homeoticchangescouldoccurinagradualmodeofevolutionSattler,1988).However,giventhatfullconversionsinorganidentityusuallytakeplaceinamutantindividualjustbythemutationofasinglehomeoticgene,ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 asaltationalmodeofcharacterchangeappearsmoreplausible,atleastfromageneticpointofview.This,however,wouldbecontradictorytotheassumptionoftheSyntheticTheorythatallkindsofevolutionaregradualandbasedonchangesinallelefrequencyatmanyloci.Anditwouldhaveaquitedramaticconsequence:homeoticmutantsshouldrepresentimportantstepsduringamacroevolutionarytransition.Sincehomeoticmutantscanbeconsideredasprofoundvariantsofanyorganismicdesign,theymightreasonablybecalledhopefulmonsters.Remarkably,Goldschmidtalreadystudiedhomeoticmutantsinthefruit”yDrosophilasuchaspodopterabecauseheconsideredthemasexcellentcandidatesforhopefulmonsters(reviewedbyDietrich,2000,2003).Butnowevo-devohasincreasedtheevolutionarycredibilityofdrasticsaltational,yetcoordinatedmorphologicalchangesasrepresentedby”oralhomeotictransitions(BatemanandDiMichele,2002Krameretal.,2003Theißenetal.,2000Theißenetal.,2002Thus,thankstothehelpfulmonsters(Coen,2001)providedbydevelopmentalgenetics,hopefulmonstersarebackonthecentrestageofevolutionarybiology.ThereturnofhopefulmonstersTheconceptofhopefulmonsterswouldhaveremainedasdeadasaDodoifanyorthodoxevolutionarytheorycouldfullyexplaintheoriginanddiversi“cationoflifeasweknowit.Butthereisnosuchcomprehensivetheory,andintheirattemptsto“llthegapsofexistingones,notonlyhasevo-devodeveloped,hopefulmonstershavealsobeenreconsideredseveraltimes.InakindofGoldschmidtvariationGould(1977a)arguedthatthefossilrecordprovidesverylittleevidenceforagradualisticmodeofmacroevolution,becausethetransitionsbetweenmajorgroupsoforganismsarecharacteristicallyabrupt.Thisobservationisusuallyattributedtothenotoriousincompletenessofthefossilrecord,butwithincreasingsamplingandintensifyingstudyofthefossilrecorditisbecominglessandlessconvincing(GouldandEldredge,1993).Evenmoreimportantisthenotionthattherearemanycasesofmacroevolutionaryeventsforwhichareasonablestoryofcontinuouschangecannotbeconstructed(Gould,1977a).Usingthephrasewhatgoodishalfawing?Gould(1977a)outlinedthatinquiteafewcasesintermediatestagesmighthavehadafunctiondifferentfromthe“nalstructure(e.g.,thehalfwingmayhavehelpedintrappingpreyorcontrollingbodytemperature),aconcepttermedpreadaptation.AccordingtoGould(1977a),however,inmanycasesgradualismcannotbesavedthatway.Forexample,ontheislandofMauritiustwogeneraofsnakesshareafeaturepresentinnootherterrestrialvertebrate,namelysplittingofthemaxillaryboneoftheupperjawintofrontandrearhalvesconnectedbyamoveablejoint.Howcanajawbonebehalfbroken(Gould,)?Adetailedconsiderationofthecaserejectedeverypreadaptivepossibilitythatcametomindinfavourofadiscontinuoustransition(Frazzetta,1970).ThisandothercasesledGould(1977a)toaccepttheoccurrenceofdiscontinuoustransitions(saltation)inmacroevolution.Accordingtothisview,theabsenceofintermediateARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369359 formsdoesnotsimplyre”ecttheincompletenessofthefossilrecord,butoftenthetruelackofsuchforms.FollowingDarwinsfriendThomasHenryHuxley,Gould(1977a)arguedthatgradualismisnotanecessarycorollaryofevolutionbynaturalselection,andthatitisthereforeunnecessarythatitbecamethecentraltenetoftheSyntheticTheory.Hesuggestedthatthesaltationalchangeofthehopefulmonstermaynotproduceaperfectformallatonce,butrathermayserveasakeyadaptationtoshiftitspossessortowardsanewmodeoflife.Inasecondphasealargesetofcollateralalterationsmayariseinamoretraditional,gradualwayoncethekeyinnovationforcesaprofoundshiftinselectivepressures.Gould(1977a,b)agreedwithGoldschmidtthatmajorevolutionarytransitionsmaybeaccomplishedbysmallalterationsintherateofearlydevelopmentthataccumulatethroughgrowthtoyieldprofounddifferencesamongadults.Gould(1977a)predictedthatGoldschmidtsideasaboutevolutionwillbelargelyvindicatedintheworldofevolutionarybiologyduringthe1980s.Asweallknow,hewaswrong.However,hopefulmonsterswereindetailrevisitedbyBatemanandDiMichele(1994,2002)intheirconceptofneoGoldschmidtiansaltation.Weowetotheseauthorsthe“rstdetailedelaborationofascienti“cconceptofhopefulmonsters.Theauthorsde“nedsaltationalevolutionasageneticmodi“cationthatisexpressedasaprofoundphenotypicchangeacrossasinglegenerationandresultsinapotentiallyindependentlineagethattheytermedprospecies.TheseprospeciesarejustGoldschmidtshopefulmonstersbyanothername(whichiswhythetermisnotadoptedhere).BatemanandDiMichele(1994,2002)discussseveralputativemechanismsofsaltationalevolution,andhowtheycouldbringaboutspeciationandprofoundphenotypicnovelties.Studyingfossilseed-fernsandextantorchidsBatemanandcolleaguesrealizedthatvastnumbersofhopefulmonstersaregeneratedcontinuouslybyheterotopy(includinghomeosis)andheterochronyduetomutationsinkeydevelopmentalgenesthatcontrolmorphogenesis(BatemanandDiMichele,2002RudallandBateman,2002,2003).Theauthorsassumethatthe“tnessofthehopefulmonstersthusgeneratedis,atleastinmostcases,toolowtosurvivecompetition-mediatedselection.Theyconcludethattheestablishmentofhopefulmonstersismostlikelyundertemporaryreleasefromselectioninenvironmentsoflowbioticcompetitionforresources,followedbyhoningtocompetitive“tnessbygradualreintroductiontoneoDarwinianselection.BatemanandDiMichele(2002)concludetheirconsiderationsbythecatchystatementthatevolutionequalsphyleticgradualisminDNAsequencespluspunctuatedequilibriainmorphology.(Phyleticgradualismreferstotheoftenalmostmolecularclock-likechangesinDNAsequencesbutthusignoresthatgeneneticchangescanalsobepunctuated,e.g.inthecaseofgene,chromosomeorevengenomeduplications).Inadditiontotheseconceptualconsiderationshopefulmonstershavebeenconsideredasreasonablehypothesesinindividualcasesofmacroevolutionwherescenariosofgradualevolutionappearedimplausible.Arguablythemoststrikingcaseisprovidedbytheoriginofturtles(Testudines).Turtleshavethemostunusualbodyplansoftheamniotes,withadorsalshellconsistingofmodi“edribs(Fig.2AVentralribsarenotformed,insteadthedermalplastroncoverstheventralbody.ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 Moreover,incontrasttothesituationinothervertebratespeciesinwhichthescapuladevelopsoutsidetheribcage,theshouldergirdleisfoundinsidetheribcageinturtles(Rieppel,2001).Forsuchasituationaplausiblescenarioofcontinuouschangefromanykindofpossibleancestorcannotbeconstructed(Rieppel,2001).Inlinewiththis,turtlesappearabruptlyinthefossilrecordofthelateTriassic,withnointermediatechangessofarbeingfound(reviewedbyOhyaetal.,2005).Eventhoughthisdoesnotcompletelyruleoutthatmanyintermediateformsonceexisted,itatleastsuggeststhattheturtlebodyplanoriginatedquickly,especiallysinceonecannotsaythatturtleboneshavealowpotentialtofossilize(aseriousprobleminothercasesofrapidappearanceofnovelties,e.g.originof”owers,seebelow).Thereismeanwhileevidencethattheturtlebodyplanoriginatedduetochangesinaxial-levelspeci“calterationinearlydevelopment,causedbychangesintheexpressiondomainofsomegenes(Ohyaetal.,2005Duetotheirstrikingevolution,Rieppel(2001)consideredturtlesashopefulmonsters.However,turtleshaveafossilrecorddatingbackmorethan200millionyearsandarewidespreadinmanypartsoftheworld,withanumberofspeciesfoundARTICLEINPRESS Fig.2.Putativedescendantsofhopefulmonsters.(A)Turtles(Testudohermannii)and(B)”oweringplants(in”orescenceofanorchidspecies)areprimecandidatesforowingtheirbodyplanstosaltationalevolutionviahopefulmonstersratherthanthegradualevolutionenvisagedbytheSyntheticTheory.G.Theißen/TheoryinBiosciences124(2006)349…369361 insomeofthedriestdesertsandthedeepestseas.Turtlesarethusneithermonstersnorjusthopeful,butwelladaptedandsuccessfulorganisms.Itwouldbemoreappropriatetosay,therefore,thatturtlesaredescendantsofhopefulmonstersratherthanhopefulmonstersthemselves.Cambrianexplosionandabominablemystery:hopingforhopefulWehavealreadyseenthatinsomecases,suchastheturtlebodyplan,thereisevidencethatsaltationaleventssuchashomeotictransitionscontributedtotheoriginofevolutionarynovelties.Buthowimportanthavetheseeventsbeenforglobalbiodiversity?Inprincipletheycouldrepresentexceptionalcasesthatdonotjustifyageneralrevisionofevolutionarybiology.Butthisisprobablyfarfromthetruth.Thestructuraldiversityofmulticellularorganismsonourplanetappearstohaveoriginatedtoalargeextentintwomajorbursts.ThefossilrecordsuggeststhatduringtheCambrianExplosionabout540millionyearsagothevisiblebodyplansof(almost)allanimaltaxa(extantandextinct)originatedwithinafewmillionyearsPhilippeetal.,1994Forteyetal.,1997Valentineetal.,1999).Thisdoesnotnecessarilymean,however,thattherespectiveanimalcladesalsooriginatedduringthattime;somemolecularsurveysofanimalphylogenysuggestanextendedbutcrypticPrecambrianhistoryofmetazoans(Wrayetal.,1996Levintonetal.,2004ThiswouldbeinlinewiththenotionofBatemanandDiMichele(2002)evolutionequalsphyleticgradualisminDNAsequences(includingcladogenesis)pluspunctuatedequilibriainmorphology,anditwouldrequireanexplanationofhowgraduallychanginggenescanbringaboutsaltationalchangesinmorphology.Thehypotheticalanswerfavouredhereisthatchangesinjustalimitednumberofdevelopmentalcontrolgenesgeneratinghopefulmonstersaresometimeskeytomorphologicaltransitions,whilethevastmajorityofthegenomemaychangemoreorlessinaclock-likewaywithnotmuchimpactontheoriginofmorphologicalnoveltiesandtheevolutionofbodyplans.Anyway,inmanyrespects,suchasnumberofspecies,theinsects,whichoriginatedintheCarboniferous,becamebyfarthemostsuccessfulgroupofanimals(Carroll,2001Morethan300millionyearsaftertheCambrianexplosion,inthelateJurassicorearlyCretaceous,theoriginanddiversi“cationofthe”oweringplants(angiosperms)providedthesecondexampleofanapparentlysuddenoriginandrapidearlymorphologicalradiation.Theoriginandearlydiversi“cationofangiospermswasconsideredanabominablemysteryandperplexingphenomen-onbyCharlesDarwinabout150yearsago,andhasremainedaconsiderablescienti“cchallenge(Crepet,2000Theißenetal.,2002Frohlich,2003FrohlichandParker,2000Stuessy,2004TheißenandBecker,2004Forboththeoriginofanimalsandofangiospermsthereisnofossilrecordthatwouldsupportagradualmodeofevolution,suggestingthatsaltationalevents,ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 andhencehopefulmonsters,havebeeninvolved.Nevertheless,manyattemptshavebeenmadetoexplaintheoriginofdiverseanimalsandangiospermsinagradualisticway,butconclusiveexplanationsthatstoodthetestoftime(includingexperimentalevidenceandfossildata)havenotbeenprovided.Onthecontrary,allrecenthypothesesabouttheoriginofthe”ower,forexample,postulatecriticalchangesinhomeoticgenesthatbroughtaboute.g.heterotopyorhomeosisTheißenetal.,2002TheißenandBecker,2004FrohlichandParker,2000Frohlich,2003Albertetal.,2002).Theoriginoftheangiosperm”owerthusbecamearguablythebeststudiedbotanicalcaseofcon”ictbetweentheSyntheticTheoryaccountandnon-gradualisticmodelsofevolutionarykeyinnovations(Vergara-Silva,2003Intermsofspeciesandecologicaldominanceanimalsand”oweringplantsbecameextremelysuccessfulgroupsoforganisms.Adaptiveradiationandco-evolutionbetweenbothgroups,e.g.duetoplant…pollinatorandplant…predatorinteractions,havecertainlyplayedagreatroleinthis.Butthe“rststepsmighthavebeenmadebysomestrangeorganismsthatmanagedtoovercomethedevelopmentalconstraintsoftheirancestorsandhenceacquiredkeyinnovationsthatweretheprerequisiteforanyadaptiveradiationandco-evolutionaryprocessthatfollowed.Ifanimalandangiospermbodyplansreallyoriginatedviahopefulmonsters,theimportanceofhopefulmonstersforthebiodiversityonourplanetcanhardlybeoverestimated.ThefutureofhopefulmonstersWhatsinaname?Ahopefulmonster,byanyothername(e.g.,prospecies),wouldremainaremarkable,andcontroversial,concept.Inordertoestablishhopefulmonstersasausefuladditiontoevolutionarybiology,however,theconcepthastobere“ned,andtestedempirically.(a)Thinkingintermsofmutuallyexclusivealternativeshastobeovercome.Neitherdoesitappearlikelythatmacroevolutionproceedsexclusivelybytheraresuccessofhopefulmonsters(asassumedbyGoldschmidt),northatitalwaysproceedsbyanaccumulationofsmallchangeswithinpopulations(asmaintainedbytheSyntheticTheory).Rather,therelativeimportanceofbothmodesofmacroevolutionhastobedetermined.Thisimpliesthat,incontrasttoGoldschmidtsviews,evolutionaboveandbelowthespecieslevelisnotgovernedbycompletelydifferentprocesses,andthatbothgradualaswellassaltationaleventsbridgedthegapsthatGoldschmidtsawbetweenspecies.(b)Becausetheimportanceofsaltationalevolutionmightbedifferentindifferentkindsoforganisms,evolutionarybiologyhastoovercomeitsinordinatefondnessforanimals.EvolutionarybiologyhasbeenzoocentriceversinceDarwinstime(BatemanandDiMichele,2002).Butanimals,withtheirhighlyARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369363 conservedbodyplansfullyoutlinedduringembryogenesis,arearguablythegroupoforganismsinwhichhopefulmonstersaretheleastlikelytoappear(butnevertheless,somemighthaveexisted,seeabove).Plants,withtheiropen,additivegrowthandtheirgreatpotentialforself-fertilizationandclonalvegetativereproduction,aremuchbettercandidates(BatemanandDiMichele,).Soinordertoassesstheevolutionaryimportanceofhopefulmonsters,evolutionarybiologyhastocoverthediversityoflifeinalessbiasedway.PossiblyGoldschmidtwasrightinassumingthathomeoticmutantsareofconsiderableevolutionaryimportance,hejustmighthavelookedatthewrongspecies.(c)Ithastobemoreappreciatedthatalongthecontingenttrajectoriesofreplicatingorganismsrarityofeventsdoesnotnecessarilyimplyunimportance.Innaturalpopulationshopefulmonstersmightberare(thoughmorefrequentthanmanyassume),andsuccessfulhopefulmonstersmightbemuchrarerstill.Butevenifhopefulmonstersareasrareasmeteoritesthathittheearth,theycouldbeofenormousevolutionaryimportance.ThemeteoritethatprobablywipedoutthedinosaursandmanyotherorganismsattheendoftheCretaceous65millionyearsagocertainlyhadanenormousimpactonthefaunasand”orasonearth.ButiftheCambrianExplosionortheoriginoftheangiospermsinvolvedhopefulmonsters,theydidnothavealesserimpactonthebiodiversityofourplanet.(d)Putativehopefulmonstershavetobeexperimentallystudiedandnotjustdiscussed.Whileevo-devohasprovideddetailedinformationastohowhopefulmonsterscanbegenerated,almostnothingisknownabouttheirperformanceinnaturalenvironments.Thusthepopulationdynamicsofhopefulmonstershastobestudiedinextensive“eldwork(Theißen,2000BatemanandDiMichele,2002Vergara-Silva,2003Dietrich,2003).Non-gradualmodesofevolutionwillnotbegenerallyacceptedunlessasuf“cient“tnessofhopefulmonstershasbeendocumentedinnaturalhabitats.Towardsthatgoal,promisingcandidatesforhopefulmonsters“rsthavetobeidenti“edamongextantspecies.Floralhomeoticmutantsagainappeartobeagoodstudyobjecttous,butofcoursenoteverymutantfreakwilldo.Sterilemutantsthathavetransformedtheirreproductiveorgans(Fig.1B)canbereadilyclassi“edashopeless.Agoodstartingpointmightthusbe”oralhomeoticmutantsthatappearinpopulationsinthewild,thusrevealingatleastsomeminimal“tness.Veryfewofthemhavebeendescribed,including,arecessivevarietyofClarkiaconcinna(Onagraceae)inwhichthepetalsaretransformedintosepaloidorgans(FordandGottlieb,1992).ItoccursonlyinasmallpopulationnorthofSanFrancisco(USA),accompaniedbyamajorityofwild-typeplants.AnothercaseisapeloricvarietyofLinariavulgarishasactinomorphicratherthanzygomorphic”owersandpersistsonasmallislandnearStockholm(Sweden)(Cubasetal.,1999).Whilethebicalyxgenehasnotbeenmolecularlycharacterizedsofar,itturnedoutthattheLinariavarietyisaffectedinaCYCLOIDEA-likegene,butbyepimutation(methylationofDNA)ratherthanchangeintheDNAsequence(Cubasetal.,ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 ).BoththeClarkiavarietieshaveaverylimitedrangeofdistribution,andtheir“tnessandcompetitivenessinthe“eldhavenotbeentestedyet,butisquestionable(theLinariaepimutantmayevenonlypropagatevegetatively;Theißen,2000).Incontrast,a”oralhomeoticvarietyofShepherdspurse(Capsellabursa-pastoris)hasbeendescribedforalmost200yearsfromdifferentlocationsthroughoutEurope,andhasbeendocumentedtoexistinpopulationsofconsiderablesizeatleastforanumberofyears(Opiz,Trattinnick,1821Murbeck,1918Dahlgren,1919Gottschalk,1971Reichert,1998).Thisdecandricvarietyhas”owersthatlackpetals(Fig.1Dsincetheyarealltransformedintostamens(decandricreferstothefactthatthevarietyhas10ratherthantheusual6stamensinthewildtype).Atleastinsomecasesthevarietyisbasedonamutationatasingle,co-dominantlocusDahlgren,1919Gottschalk(1971)concludedfromthedistributionofthe”oralhomeoticvarietythatitmusthaveaselectiveadvantagecomparedtothewildtype.Iamnotsosure,butwouldagreethatits“tnessisatleastnotseriouslyhampered.Itthusmayqualifyasahopefulmonster.Effortstocharacterizeitindetail,rangingfromthemoleculargeneticsofthemutantphenotypetoitsperformanceinwildhabitatsareunderway.Animportantquestionoffutureresearchwillbeto“ndoutwhetherepimutationsserveastransitionalstepsinatrialphaseofmutantphenotypesduringtheoriginofhopefulmonstersTheißen,2000ConcludingremarksWehaveseenabovethathopefulmonstersarenotjustpostulatedinhabitantsofCambrianfaunasandCretaceous”oras,butthattheymightstillbeamongus,havingmanyproperplacesinecologicaltermsrangingfromsomerockcliffsinCaliforniatovineyardsinGermany(FordandGottlieb,1992Reichert,1998).But,“nally,whatistheproperplaceofhopefulmonstersinevolutionarybiology?Itisdangeroustoraiseattentiontothefactthatthereisnosatisfyingexplanationformacroevolution.Oneeasilybecomesatargetoforthodoxevolutionarybiologyandafalsefriendofproponentsofnon-scienti“cconcepts.Accordingtotheformerwealreadyknowalltherelevantprinciplesthatexplainthecomplexityanddiversityoflifeonearth;forthelatterscienceandresearchwillneverbeabletoprovideaconclusiveexplanation,simplybecausecomplexlifedoesnothaveanaturalorigin.Fromaheuristicpointofview,bothpositionsareunsatisfactorily.Butthehabitatofhopefulmonstersmightbeverysmall.Itstheverynarrowplacebetweenadogmaticevolutionarybiologythatacceptsonlygradualchanges,andconceptsthatmaintainthatlivingorganismsaretoocomplextobeexplainedbythescienti“cmethod.Inotherwords,theonlyappropriateplaceforhopefulmonstersinthesedaysisinthesmallisthmusbetweentheSkyllaofdogmaticscienceandtheCharybdisofreligiousbelief.Futureprogressinevolutionarybiologymightbeanarrowescape.ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369365 AcknowledgementsIthankRolfRutishauser(ZurichUniversity),GunterP.Wagner(YaleUniversity)andRichardBateman(NHM,London)forhelpfuldiscussionsaboutmonstersofdifferentkinds.ManythanksalsotoBarbaraNeuffer(UniversityofOsnabruck),MatthiasHoffmann(HalleBotanicalGarden),andPiaNutt,JanineZiermann,ConnyBartholmesandMarenHintz(frommyowngroupattheUniversityofJena)fordiscussionsintheframeworkofourprojectonthedecandricCapsellavariety.IamgratefultoHanneloreSimon,JanineZiermannandChristianeBradaczekforproviding“gures.SpecialthankstoFindusakaCharlyforteachingmetoseehopefulaspectseveninseeminglyhopelesscases,andtoOskarforeventuallyhavingrevealedhismonstrousancestrytomeaftermorethan30years.WorkinmylabonthedecandricCapsellavarietyissupportedbyGrantTH417/4-1fromtheDeutscheForschungsgemeinschaft(DFG).Akam,M.,1998.genes,homeosisandtheevolutionofsegmentidentity:noneedforhopelessmonsters.Int.J.Dev.Biol.42,445…451.Albert,V.A.,Oppenheimer,D.G.,Lindqvist,C.,2002.Pleiotropy,redundancyandtheevolutionof”owers.TrendsPlantSci.7,297…301.Arthur,W.,2002.Theemergingconceptualframeworkofevolutionarydevelopmentalbiology.Nature415,757…764.Bateman,R.M.,DiMichele,W.A.,1994.Saltationalevolutionofforminvascularplants:aneoGoldschmidtiansynthesis.In:Ingram,D.S.,Hudson,A.(Eds.),ShapeandForminPlantsandFungi.AcademicPress,London,pp.63…102.Bateman,R.M.,DiMichele,W.A.,2002.Generatingand“lteringmajorphenotypicnovelties:neoGoldschmidtiansaltationrevisited.In:Cronk,Q.C.B.,Bateman,R.M.,Hawkins,J.A.(Eds.),DevelopmentalGeneticsandPlantEvolution.Taylor&Francis,London,pp.109…159.Baum,D.A.,Donoghue,M.J.,2002.Transferenceoffunction,heterotopyandtheevolutionofplantdevelopment.In:Cronk,Q.C.B.,Bateman,R.M.,Hawkins,J.A.(Eds.),DevelopmentalGeneticsandPlantEvolution.Taylor&Francis,London,pp.52…69.Becker,A.,Theißen,G.,2003.ThemajorcladesofMADS-boxgenesandtheirroleinthedevelopmentandevolutionof”oweringplants.Mol.Phyl.Evol.29,464…489.Bradley,D.,Carpenter,R.,Sommer,H.,Hartley,N.,Coen,E.,1993.Complementary”oralhomeoticphenotypesresultfromoppositeorientationsofatransposonatthePlena-locusofAntirrhinum.Cell72,85…95.Carroll,S.B.,1995.Homeoticgenesandtheevolutionofarthropodsandchordates.Nature376,479…485.Carroll,S.B.,2001.Chanceandnecessity:theevolutionofmorphologicalcomplexityanddiversity.Nature409,1102…1109.Coen,E.,2001.GoetheandtheABCmodelof”owerdevelopment.C.R.Acad.Sci.Paris,Sciencesdelavie324,1…8.Crepet,W.L.,2000.Progressinunderstandingangiospermhistory,success,andrelationships:Darwinsabominableperplexingphenomenon.Proc.Natl.Acad.Sci.USA97,12939…12941.Cubas,P.,Vincent,C.,Coen,E.,1999.Anepigeneticmutationresponsiblefornaturalvariationin”oralsymmetry.Nature401,157…161.Dahlgren,K.V.O.,1919.ErblichkeitsversuchemiteinerdekandrischenCapsellabursa-pastoris(L.).SvenskBot.Tidskr.13,48…60.Darwin,C.,1859.OntheOriginofSpeciesbyMeansofNaturalSelection.Murray,London.Dennett,D.,2002.In:Pagel,M.(Ed.),EncyclopediaofEvolution.OxfordUniversityPress,NewYork,pp.E83…E92.ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 Dietrich,M.R.,2000.Fromhopefulmonsterstohomeoticeffects:RichardGoldschmidtsintegrationofdevelopment,evolutionandgenetics.Am.Zool.40,738…747.Dietrich,M.R.,2003.RichardGoldschmidt:hopefulmonstersandotherheresies.Nat.Rev.Genet.4,Doebley,J.,Stec,A.,Hubbard,L.,1997.Theevolutionofapicaldominanceinmaize.Nature386,Dobzhansky,T.,1937.GeneticsandtheOriginofSpecies.ColumbiaUniversityPress,NewYork.Ford,V.S.,Gottlieb,L.D.,1992.isanaturalhomeotic”oralvariant.Nature358,671…673.Fortey,R.A.,Briggs,D.E.G.,Wills,M.A.,1997.TheCambrianevolutionaryexplosionrecalibrated.Bioessays19,429…434.Frazzetta,T.H.,1970.Fromhopefulmonsterstobolyerinesnakes?Am.Nat.104,55…72.Frohlich,M.W.,2003.Anevolutionaryscenariofortheoriginof”owers.Nat.Rev.Genet.4,559…566.Frohlich,M.W.,Parker,D.S.,2000.Themostlymaletheoryof”owerevolutionaryorigins:fromgenestofossils.Syst.Bot.25,155…170.Gailing,O.,Bachmann,K.,2000.Theevolutionaryreductionofmicrosporangiain(Asteraceae):transitiongenotypesandphenotypes.PlantBiol.2,455…461.Gehring,W.J.,1992.Thehomeoboxinperspective.TrendsBiochem.Sci.17,277…280.Gilbert,S.F.,Opitz,J.M.,Raff,R.A.,1996.Resynthesizingevolutionaryanddevelopmentalbiology.Dev.Biol.173,357…372.Goldschmidt,R.,1940.TheMaterialBasisofEvolution.YaleUniversityPress,NewHaven.Gottschalk,W.,1971.DieBedeutungderGenmutationfurdieEvolutionderP”anze.GustavFischerVerlag,Stuttgart.Gould,S.J.,1977a.Thereturnofhopefulmonsters.NaturalHist.86(6),24…30.Gould,S.J.,1977b.OntogenyandPhylogeny.HarvardUniversityPress,Cambridge,MA,USA.Gould,S.J.,Eldredge,N.,1993.Punctuatedequilibriumcomesofage.Nature366,223…227.Haag,E.S.,True,J.R.,2001.Frommutantstomechanisms?Assessingthecandidategeneparadigminevolutionarybiology.Evolution55,1077…1084.Iltis,H.H.,1983.Fromteosintetomaize:thecatastrophicsexualtransmutation.Science222,Iltis,H.H.,2000.Homeoticsexualtranslocationandtheoriginofmaize(Zeamays,Poaceae):anewlookatanoldproblem.Econ.Bot.54,7…42.Junker,T.,2004.DiezweiteDarwinscheRevolution.GeschichtedesSynthetischenDarwinismusinDeutschland1924bis1950(ActaBiohistorica,Bd.8).Basilisken-Presse,Marburg.Junker,T.,Hoßfeld,U.,2001.DieEntdeckungderEvolution.EinerevolutionareTheorieundihreGeschichte.WissenschaftlicheBuchgesellschaftDarmstadt.Kanno,A.,Saeki,H.,Kameya,T.,Saedler,H.,Theissen,G.,2003.HeterotopicexpressionofclassB”oralhomeoticgenessupportsamodi“edABCmodelfortulip(Tulipagesneriana).PlantMol.Biol.52,Kellogg,E.A.,2000.Thegrasses:acasestudyinmacroevolution.Annu.Rev.Ecol.Syst.31,217…238.Kramer,E.M.,DiStilio,V.S.,Schluter,P.M.,2003.ComplexpatternsofgeneduplicationintheAPETALA3andPISTILLATAlineagesoftheRanunculaceae.Int.J.PlantSci.164,1…11.Krizek,B.A.,Meyerowitz,E.M.,1996.TheArabidopsishomeoticgenesAPETALA3andPISTILLATAaresuf“cienttoprovidetheBclassorganidentityfunction.Development122,11…22.Lenski,R.E.,Ofria,C.,Pennock,R.T.,Adami,C.,2003.Theevolutionaryoriginofcomplexfeatures.Nature423,139…144.Levinton,J.,Dubb,L.,Wray,G.A.,2004.SimulationsofevolutionaryradiationsandtheirapplicationtounderstandingtheprobabilityofaCambrianexplosion.J.Paleont.78,31…38.Lewis,E.B.,1994.Homeosis:the“rst100years.TrendsGenet.10,341…343.nnig,W.-E.,2004.Dynamicgenomes,morphologicalstasis,andtheoriginofirreduciblecomplexity.In:Parisi,V.,DeFonzo,V.,Aluf“-Pentini,F.(Eds.),DynamicalGenetics.ResearchSignpost,Trivandrum,India,pp.101…119.Mayr,E.,1942.SystematicsandtheOriginofSpecies.ColumbiaUniversityPress,NewYork.Mayr,E.,Provine,W.B.,1980.TheEvolutionarySynthesis.HarvardUniversityPress,Cambridge,MA.Meyerowitz,E.M.,2002.Plantscomparedtoanimals:thebroadestcomparativestudyofdevelopment.Science295,1482…1485.Meyerowitz,E.M.,Smyth,D.R.,Bowman,J.L.,1989.Abnormal”owersandpatternformationin”oraldevelopment.Development106,209…217.Moritz,D.M.L.,Kadereit,J.W.,2001.ThegeneticsofevolutionarychangeinSeneciovulgarisL.:aQTLmappingapproach.PlantBiol.3,544…552.ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369367 Murbeck,S.V.,1918.UberstaminalePseudapetalieundderenBedeutungfurdieFragenachderHerkunftderBlutenkrone.LundsUniversitetsArsskriftN.F.Avd.2,Bd.14,No.25,Lund.Ohya,Y.K.,Kuraku,S.,Kuratani,S.,2005.codeinembryosofChinesesoft-shelledturtlecorrelateswiththeevolutionaryinnovationintheturtle.J.Exp.Zool.(Mol.Dev.Evol.)304B,Opiz,P.M.,1821.2.CapsellaapetalaOpiz.EineneuemerkwurdigeP”anze.FloraNr.28,oder:BotanischeZeitung,Regensburg,28.Juli1821.Philippe,H.,Chenuil,A.,Adoutte,A.,1994.CantheCambrianexplosionbeinferredthroughmolecularphylogeny?Development(Suppl.),15…25.Raff,R.A.,2005.Editorial:standupforevolution.Evol.Dev.7,273…275.Reichert,H.,1998.EinekronblattloseSippedesHirtentaschels(Capsellabursa-pastoris)seitJahrenbestandsbildendbeiGau-Odernheim/Rheinhessen.HessischeFloristischeRundbriefe47(4),Reif,W.-E.,Junker,T.,Hoßfeld,U.,2000.Thesynthetictheoryofevolution:generalproblemsandtheGermancontributiontothesynthesis.TheoryBiosci.119,41…91.Riedl,R.,1977.Asystems-analyticalapproachtomacro-evolutionaryphenomena.Quart.Rev.Biol.52,Rieppel,O.,2001.Turtlesashopefulmonsters.Bioessays23,987…991.RonseDeCraene,L.P.,2003.Theevolutionarysigni“canceofhomeosisin”owers:amorphologicalperspective.Int.J.PlantSci.164,S225…S235.Rudall,P.J.,Bateman,R.M.,2002.Rolesofsynorganisation,zygomorphyandheterotopyin”oralevolution:thegynostemiumandlabellumoforchidsandotherlilioidmonocots.Biol.Rev.77,Rudall,P.J.,Bateman,R.,2003.Evolutionarychangein”owersandin”orescences:evidencefromnaturallyoccurringterata.TrendsPlantSci.8,76…82.Rutishauser,R.,Isler,B.,2001.Developmentalgeneticsandmorphologicalevolutionof”oweringplants,especiallybladderworts():fuzzyArberianmorphologycomplementsclassicalmorphology.Ann.Bot.88,1173…1202.Rutishauser,R.,Moline,P.,2005.Evo-devoandthesearchforsamenessinbiologicalsystems.In:Richter,S.,Olsson,L.(Eds.),EvolutionaryDevelopmentalBiology:NewChallengestotheHomologyConcept?TheoryBiosci.124,pp.213…242.Sattler,R.,1988.Homeosisinplants.Am.J.Bot.75,1606…1617.Simpson,G.G.,1944.TempoandModeinEvolution.ColumbiaUniversityPress,NewYork.Stuessy,T.F.,2004.Atransitional-combinationaltheoryfortheoriginofangiosperms.Taxon53,3…16.Svensson,M.E.,2004.Homologyandhomocracyrevisited:geneexpressionpatternsandhypothesesofhomology.Dev.GenesEvol.214,418…421.Theißen,G.,2000.Evolutionarydevelopmentalgeneticsof”oralsymmetry:therevealingpowerofLinnaeusmonstrous”ower.Bioessays22,209…213.Theißen,G.,2001.Developmentof”oralorganidentity:storiesfromtheMADShouse.Curr.Opin.PlantBiol.4,75…85.Theißen,G.,2002.Orthology:secretlifeofgenes.Nature415,741.Theißen,G.,2005.Birth,lifeanddeathofdevelopmentalcontrolgenes:newchallengesforthehomologyconcept.In:Richter,S.,Olsson,L.(Eds.),EvolutionaryDevelopmentalBiology:NewChallengestotheHomologyConcept?TheoryBiosci.124,pp.199…212.Theißen,G.,Becker,A.,2004.GymnospermorthologuesofclassB”oralhomeoticgenesandtheirimpactonunderstanding”owerorigin.Crit.Rev.PlantSci.23,129…148.Theißen,G.,Becker,A.,DiRosa,A.,Kanno,A.,Kim,J.T.,Munster,T.,Winter,K.-U.,Saedler,H.,2000.AshorthistoryofMADS-boxgenesinplants.PlantMol.Biol.42,115…149.Theißen,G.,Becker,A.,Kirchner,C.,Munster,T.,Winter,K.-U.,Saedler,H.,2002.Howlandplantslearnedtheir”oralABCs:theroleofMADS-boxgenesintheevolutionaryoriginof”owers.In:Cronk,Q.C.B.,Bateman,R.M.,Hawkins,J.A.(Eds.),DevelopmentalGeneticsandPlantEvolution.Taylor&Francis,London,pp.173…205.Trattinnick,L.,1821.BotanischeBemerkungen.Flora1821,723.Valentine,J.W.,Jablonski,D.,Erwin,D.H.,1999.Fossils,molecules,andtheembryo:newperspectivesontheCambrianexplosion.Development126,851…859.Vargas,A.O.,Fallon,J.F.,2005.Birdshavedinosaurwings:themolecularevidence.J.Exp.Zool.(Mol.Dev.Evol.)304B,86…90.Vergara-Silva,F.,2003.Plantsandtheconceptualarticulationofevolutionarydevelopmentalbiology.Biol.Philos.18,249…284.ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369 Wagner,G.P.,2000.Whatisthepromiseofdevelopmentalevolution:PartI:whyisdevelopmentalbiologynecessarytoexplainevolutionaryinnovations?J.Exp.Zool.(Mol.Dev.Evol.)288,95…98.Wagner,G.P.,Gauthier,J.A.,1999.1,2,32,3,4:asolutiontotheproblemofthehomologyofthedigitsintheavianhand.Proc.Natl.Acad.Sci.USA96,5111…5116.Wagner,G.P.,Laubichler,M.D.,2004.RupertRiedlandthere-synthesisofevolutionaryanddevelopmentalbiology:bodyplanandevolvability.J.Exp.Zool.(Mol.Dev.Evol.)302B,92…102.Wagner,G.P.,Muller,G.B.,2002.Evolutionaryinnovationsovercomeancestralconstraints:are-examinationofcharacterevolutioninmalesepsid”ies(Diptera:Sepsidae).Evol.Dev.4,1…6.Wang,H.,Nussbaum-Wagler,T.,Li,B.,Zhao,Q.,Vigouroux,Y.,Faller,M.,Bomblies,K.,Lukens,L.,Doebley,J.F.,2005.Theoriginofthenakedgrainsofmaize.Nature436,714…719.Wang,R.-L.,Stec,A.,Hey,J.,Lukens,L.,Doebley,J.,1999.Thelimitsofselectionduringmaizedomestication.Nature398,236…239.Weiss,K.M.,2005.Thephenogeneticlogicoflife.Nat.Rev.Genet.6,36…46.Wray,G.A.,Levinton,J.S.,Shapiro,L.H.,1996.MolecularevidencefordeepPrecambriandivergencesamongmetazoanphyla.Science274,568…573.Wright,S.,1941.ThematerialbasisofevolutionbyR.Goldschmidt(review).Sci.Monthly53,165…170.ARTICLEINPRESSG.Theißen/TheoryinBiosciences124(2006)349…369369