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Origin of Animals

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EvolutionofDevelopment:EvolutionofAnimalBodyPlansasanExample

Or,anotherwaytoconceptualizetoday’slecture:

EvolutionofGeneRegulatoryNetworks:

EvolutionofDevelopmentasanExample

• WhatisanAnimal?• Whatmakesthemdifferentfromotherorganisms?

• WhendidtheyEvolve?• HowdidtheyEvolve?

Multicellular (metazoan)Heterotrophic (eat, not photo or chemosynthetic)

Eukaryote

No Cell Walls, have collagenNervous tissue, muscle tissue

Particular Life History-developmental patterns (this lecture)

WhatisanAnimal?

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• http://www.wimp.com/planktonlife/

Aretheredifferencesbetweenplantandanimalevolution?

• Greaterdiversityinsexualsystemsinplants

– Abundantasexuality

• Morechemistrylessbehaviorinplants

• Developmentislessrigidandregulatedinplants:perhapsallowingformoreevolutionby“hopefulmonsters,”asdevelopmentalabnormalitiesaremoretolerableinplants

• Polyploidyistoleratedmorereadilyandcommoninplants

Outline• Today:Biggerpictureonhowradicalchangesinbodyplancomeabout

• EvolutionofDevelopment• EvolutionofDevelopmentalGeneRegulatoryNetworks(GRNs)

• HierarchyinEvolutionofGRNs• EvolutionofGRNs leadingtoevolutionofmajorphylogeneticbreaksinEarthHistory

Outline

• NextLectures:HumanEvolution…agreatexampleofEvolutionofDevelopment

• Mostdifferencesbetweenhumansandotherprimatesareduetoevolutionarychangesatafewdevelopmentalgenes

Reviewconceptsfrompreviouslectures:

• cis- andtrans-regulation• Transcriptionfactors• Pleiotropy• CambrianExplosion• Phylogeny

EvolutionofDevelopment:

• Whatisit?

• Howcanitleadtoevolutionofradicalchangesinbodyplan?

• Howcandifferenttypesofdevelopmentalchanges(mutationsatdifferentdevelopmentalstages)leadtodifferenthierarchicalevolutionarychanges(thatdistinguishphylum,class,order,family,genus,species)?

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OntogenyRecapitulatesPhylogenyErnstHaeckel(1834-1919)

• Ontogenyisthecourseofdevelopmentofanorganismfromfertilizedeggtoadult;phylogenyistheevolutionaryhistoryofagroupoforganisms.

• Haeckelobservedthatasembryosofvertebratesdeveloped,theypassedthroughstagesthatresembledtheadultphaseofmoreancestral(“primitive”)organisms.Forexample,atonepointeachhumanembryohasgillsandresemblesatadpole.

• Haeckel’sideawasthataspecies’biologicaldevelopment,orontogeny,parallelsandsummarizesthespecies’evolutionaryhistory,orphylogeny

OntogenyRecapitulatesPhylogenyErnstHaeckel(1834-1919)

• Someofhisanalogieshavebeendiscredited(infavorofVonBaer’sideas)

• However,Haeckel'sgeneralconcept,thatthedevelopmentalprocessrevealssomecluesaboutevolutionaryhistory,appearstoholdfortheevolutionofdevelopmentalgenes.

Romanes's 1892copyofErnstHaeckel’sembryonicdrawings

TheCambrianExplosion

65mya:CretaceousExtinction(dinosaursgoextinct)

230 mya: Permian Extinction

570 mya: Cambrian Explosion

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EvolutionofAnimalBodyPlans

• TrueTissues• TissueLayers(Diplo vs Triploblasts)• BodySymmetry• Evolutionofbodycavity(Coelom)• EvolutionofDevelopment

Cambrian Explosion

Howcouldthishappen?(geneticmechanism?)

TheEvolutionofDevelopment(Freeman&Herron,Chapter19)

• ThetremendousincreaseindiversityduringtheCambrianexplosionappearstohavebeencausedbyevolutionofdevelopmentalgenes

• Changesindevelopmentalgenescanresultinradicallynewmorphologicalforms

• Developmentalgenescontroltherate,timing,andspatialpatternofchangesinanorganism’sformasitdevelopsintoanadult

• ThediscoveryofHox genes– Notthe“mostimportant”devgenes– Nottheonlydevelopmentalgenes– But,amongthefirststudied

Hox genesaretypesofHomeotic genes,whicharegenesthatcontrolthepatternsandorderofdevelopmentinplantsandanimals.Forexample,homeoticgenesareinvolvedindeterminingwhere,when,andhowbodysegmentsdevelopinorganisms.

ExamplesofHomeotic genes:Hox genes,paraHox genes,MADS-boxcontaininggenes,etc.

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Changesinafewregulatorygenescouldhavebigimpacts

• Mostnewfeaturesofmulticellularorganismsarisewhenpreexistingcelltypesappearatnewlocations ornewtimes intheembryo.

• Changesinthespecificationofcellfates areamajormechanismfortheevolutionofdifferentorganismalforms.

• Forexample,smallchangesingeneregulationcouldcausechangesintimingofdevelopmentalevents(heterochrony),whichcouldthenleadtodramaticchangesinmorphology

• StephanJayGouldin1977proposedthisasamechanismforevolutionarychange

So,whathappenedduringtheCambrianExplosion?

AllmajorAnimalPhyla(differentbodyplans)evolvedwithinarelativelynarrowwindowoftime

(1)Precambrian-PaleozoicBoundary (~570MYA)

Cambrian Explosion

Prec

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Cambrian

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1200

1000

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Anne

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Arth

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0Million Years Ago

Wray et al. 1996

BasedonphylogenyofanimalsbasedonDNAsequencedata,theradiationofanimalspredatesthegeologicalrecordoftheCambrianExplosion

“CambrianExplosion”Howcandifferenttypesofdevelopmentalchangesleadtodifferenthierarchicalevolutionarychanges(thatdistinguishphylum,class,order,family,genus,species)

TheGrandMystery

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WhyhastherehasbeensolittlechangeinanimalbodyplanssincetheCambrianExplosion???

TheGrandMystery

Davidson&Erwin.2006.GeneRegulatoryNetworksandtheEvolutionofAnimalBodyPlans.Science.311:796-800.

Bigphylogeny

“Kernels”

“GeneBatteries”

1. ‘‘Kernels’’oftheGRN: Evolutionarilyinflexiblesubcircuits (ofregulatorygenes)thatperformessentialupstreamfunctionsinbuildinggivenbodypartsàmaindifferencesamongphyla

2. ‘‘Plug-ins’’oftheGRN: Certainsmallsubcircuits (ofregulatorygenes),thathavebeenrepeatedlyco-optedfordiversedevelopmentalpurposes

3. Input/Output(I/O)deviceswithintheGRN: Switchesthatallowordisallowdevelopmentalsubcircuits tofunctioninagivencontext(e.g.Hox genes)

4. DifferentiationGeneBatteries: Consistofgroupsofprotein-codinggenesundercommonregulatorycontrol,theproductsofwhichexecutecelltype–specificfunctionsà Speciesdifferences

DifferentHierarchicalComponentsofGeneRegulatoryNetworks

First,BasicsonDevelopmentalGeneRegulatoryNetworks

DevelopmentalGeneRegulatoryNetwork

• ThebindingoftranscriptionfactorstoregulatoryDNAsequencescontrolsthespatialandtemporalexpressionofgenesinthedevelopingorganism

• Becauseeachtranscriptionfactorregulatestheexpressionofmultiplegenes,regulatorygeneinteractionsformanetwork.

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S.Sinha

DevelopmentalGeneRegulatoryNetwork

• ThebindingoftranscriptionfactorstoregulatoryDNAsequencescontrolsthespatialandtemporalexpressionofgenesinthedevelopingorganism

• Becauseeachtranscriptionfactorregulatestheexpressionofmultiplegenes,regulatorygeneinteractionsformanetwork.

DevelopmentalGeneRegulatoryNetwork

Exampleshownforneuraldevelopment

DevelopmentalGeneRegulatoryNetworks(GRNs)

• Developmentiscontrolleddirectlybyprogressivechangesintheregulatorystateinthespatialdomainsofthedevelopingorganism.

• Asregulatorygenesregulateoneanotheraswellasothergenes,andbecauseeveryregulatorygenerespondstomultipleinputswhileregulatingmultipleothergenes,thetotalmapoftheirinteractionshastheformofanetwork.

• GeneRegulatoryNetworksconsistof:• Regulatorygenes,whichencodetranscriptionfactors• Signalinggenes,whichencodeligands andreceptorsforintercellularcommunication

Whatkindofevolutionarychanges(i.e.mutations)leadtotheevolution

ofGeneRegulatoryNetworks?

EvolutionaryChangeswithintheGeneRegulatoryNetworks• DevelopmentalBiologistshavehypothesizedthatmostchangeswithinregulatorynetworkswouldbe cis-regulatory (e.g.promoter,enhanceratthegene)

• Thereasonisthatcis-regulatorychangeswouldonlychangetheexpressionofonegene

• Ontheotherhand,Trans-regulatorychangesareoftenoverlypleiotropic,andthusdon’toccurasoften.But,whentheyoccur,theyhaveprofoundeffects.

• So,developmentalevolutionarychangeshavebeenassumedtobemostlycis-regulatory.

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DevelopmentalGeneRegulatoryNetworks(GRNs)

• Comparativedevelopmentalevidenceindicatesthatreorganizationsindevelopmentalgeneregulatorynetworks(GRNs)underlieevolutionarychangesinanimalmorphology,includingbodyplans.

• ThenatureoftheevolutionaryalterationsthatarisefromregulatorychangesdependsonthehierarchicalpositionofthechangewithinaGRN.

DevelopmentalGeneRegulatoryNetworks(GRNs)

• GRNs arehierarchical,sothattheportionscontrollingtheinitialstagesofdevelopmentareatthetopofthehierarchy(earlyindevelopment),theportionscontrollingintermediateprocessesofspatialsubdivisionortheformationoffuturemorphologicalpatternareinthemiddle,andtheportionscontrollingthedetailedfunctionsofcelldifferentiationandmorphogenesisareattheperiphery.

DevelopmentalGeneRegulatoryNetwork

Exampleshownforneuraldevelopment

Thefundamentaldifferences

“Kernels”

“GeneBatteries”

Developmentoccursthroughasequenceofevents

• DuringDevelopment,regulationofgeneexpressioniscriticalfordeterminingthedifferentialfateofgeneticallyidenticalcells

• Morphologicalpatterningduringthecourseofdevelopment:Generalà moredetailed

• Developmentalchangesleadtodivergenceatdifferenthierarchicallevelsfromthemoreupstream“kernels”earlyindevelopment,tothemoreperipheral“genebatteries”

• Ontogenyrecapitulatesphylogeny: Christiane Nüsslein-Volhard and Sean Carroll

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OntogenyRecapitulatesPhylogenyErnstHaeckel(1834-1919)

• Haeckel’sideawasthataspecies’biologicaldevelopment,orontogeny,parallelsandsummarizesthespecies’evolutionaryhistory,orphylogeny

• Haeckel'sgeneralconcept,thatthedevelopmentalprocessrevealssomecluesaboutevolutionaryhistory,mightgenerallyholdfortheevolutionofdevelopmentalgenes.

Christiane Nüsslein-Volhard and Sean Carroll

Architecturalchangesinanimalbodyplansmighthavebeenproducedoverthepast600millionyearsbychangesinGRNs (generegulatorynetworks)ofmultipleclasses,withextremelydifferentdevelopmentalconsequencesandratesofoccurrence.

• Themodularsub-circuitsofdevelopmentalGRNs differinevolutionarylability.

• Themostslowlychangingcomponents— calledkernels— consistofhighlyconservedregulatoryinteractionsthatestablishtheprogenitorfieldofadevelopingstructure.

• Theevolutionarystability(constraint)ofkernelscontrastswiththelability(evolvability)ofotherGRNsub-circuits.

EvolutionofGRNs

1. ‘‘Kernels’’oftheGRN: Evolutionarilyinflexiblesubcircuits (ofregulatorygenes)thatperformessentialupstreamfunctionsinbuildinggivenbodypartsàmaindifferencesamongphyla

2. ‘‘Plug-ins’’oftheGRN: Certainsmallsubcircuits (ofregulatorygenes),thathavebeenrepeatedlyco-optedfordiversedevelopmentalpurposes

3. Input/Output(I/O)deviceswithintheGRN: Switchesthatallowordisallowdevelopmentalsubcircuits tofunctioninagivencontext(e.g.Hox genes)

4. DifferentiationGeneBatteries: Consistofgroupsofprotein-codinggenesundercommonregulatorycontrol,theproductsofwhichexecutecelltype–specificfunctionsà Speciesdifferences

DifferentHierarchicalComponentsofGeneRegulatoryNetworks

1. ‘‘Kernels’’oftheGRN: Evolutionarilyinflexible(constrained)subcircuits thatperformessentialupstreamfunctionsinbuildinggivenbodyparts

• Oftendedicatedtomajorformationofbodyparts• Oftensub-circuitofinteractingtranscriptionfactors• Oftenhighlyconstrainedbypleiotropy• Oftencannotundergoevolutionarychangewithout

catastrophiceffects

• Examplesinnextfourslides.OtherpossibleExamples:anteriortoposteriorandmidlinetolateralspecificationofthenervoussystem(indeuterostomes andpossiblyacrossBilateria);eyefield specification[inarthropods];gutregionalization[inchordates];developmentofimmunesystems[acrossBilateria];andregionalizationofthehindbrainandspecificationofneuralcrest[inchordates]

DifferentComponentsofGeneRegulatoryNetworks

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• Kernelsaresub-circuitscomposedofrecursivelywiredregulatorygenes(thatis,theyshareinputsthroughmultiplecis-regulatoryinteractions),whichoperateduringtheinitialphaseofregionalpatternformationforaparticularbodypart.

• Ifanyofthegenesinthesub-circuitarepreventedfromfunctioning,thebodypartfailstodevelop.

• Akernelinteractswithregionalregulatorystatesub-circuits,whichinturnactivateorrepresstheactivityofdifferentiationgenebatteriesattheperipheryoftheGRN(nextfigures).

• TheconservedstructureofdevelopmentalGRNkernelsmightberesponsibleforthephenotypicstabilityofanimalbodyplansthathaspersistedatleastsincetheEarlyCambrianperiod,520millionyearsago.

‘‘Kernels’’oftheGRNEndomesoderm specificationkernel,commontoseaurchinandstarfish,thelastcommonancestorofwhichlivedabouthalfabillionyearsago.

Fiveofthesixgenesinthekernel(allexceptdelta)encodeDNA-recognizingtranscriptionfactors

Thelinkagesarehighlyrecursive.Thecis-regulatorymoduleoftheotx genereceivesinputfromthreeofthefivegenes;thefoxa gene,fromthreeofthefive;andthegatae,foxa,andbragenesfromtwoofthesamefivegenes

Possibleheartspecificationkernels;assembledfrommanyliteraturesources.Dashedlinesshowpossibleinteractions.

Thesenetworksarealsohighlyrecursive

Acoresetofregulatorygenesareusedincommonandarelinkedinasimilarwayinaconservedsubcircuit ofthegenenetworkarchitecture(greyboxes)

GeneralModelforHeartSpecificationKernel

Zebrafish endodermkernel(subcircuit)

Photoshowsgeneexpressionof4transcriptionfactorsthatarepartofthiskernel

Tsengetal.2011

1. blank

2. ‘‘Plug-ins’’oftheGRN: Certainsmallsubcircuits thathavebeenrepeatedlyco-optedfordiversedevelopmentalpurposes

• Notdedicatedtoformationofbodyparts.Instead,theyareinsertedinmanydifferentnetworkswheretheyprovideinputsintoagreatvarietyofregulatoryapparatus.

• Oftenexpresseddifferentiallyinthe(species-specific)terminalphasesofdevelopment

• Theirconnectionsintothenetworkareevolutionarilyverylabile(evolvable)

• Examples:signaltransductionsystems,Wnt,transforminggrowthfactor–b (TGF-b),fibroblastgrowthfactor,Hedgehog,Notch,andepidermalgrowthfactor

DifferentHierarchicalComponentsofGeneRegulatoryNetworks

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SonicHedgehog signalingpathway:

Keyroleinregulatingvertebrateorganogenesis,suchasinthegrowthofdigitsonlimbsandorganizationofthebrain.

SonicHedgehog(yellow)signalingcontrollingneuronalidentityinthedevelopingspinalcord

3. Input/Output(I/O)deviceswithintheGRN:Switchesthatallowordisallowdevelopmentalsubcircuits tofunctioninagivencontext

• Permitorprohibittheoperationoftheregulatorysub-circuits,andsignalsbetweentheregulatorysub-circuits

• Theycanacttopermitorprohibitpatterningsubcircuitsfromactingingivenregionsofananimal.

• Examples:regulationofsizeofhomologousbodyparts.regulationoffateofsegmentsinanimalshox genes,Ubx,pitx2

DifferentHierarchicalComponentsofGeneRegulatoryNetworks

Hox Genes

• Hox genesareexamplesof“Input/OutputDevices”…thatis,operatelike“on/off”switches

• Iftheyare“on”withinananimalregion,theywilldictatethefateofthatsegment

• Hox genesaretranscriptionfactors,whichregulategenesthatinturnregulatelargenetworksofothergenes

Hox Clusters

• Genefamilyformedbygeneduplicationevents

• Hox geneproductsare transcriptionfactors,regulatoryproteinsthatbindtoDNAandcontrolthetranscriptionofothergenes

• Hox genesdeterminetheidentityofsegmentalregionsalongtheanterio-posterioraxisofanimalsduringearlyembryonicdevelopment(e.g.legs,antennae,andwingsinfruitfliesorthedifferentvertebrateribsinhumans)

• Hox genesareaclassofhomeotic genesthatprovidepositionalinformationduringdevelopment

• IfHox genesareexpressedinthewronglocation,bodypartscanbeproducedinthewronglocation

• Forexample,incrustaceans,aswimmingappendagecanbeproducedinasegmentinsteadofafeedingappendage

Hox Genes MutationsinaHox genecausinglegstogrowoutofthehead

In this case, the identity of one head segment has been changed to that of a thoracic segment.

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Hox genes in Drosophila

Hox genestendtobeclusteredalongachromosomeintheorderthattheyareexpressedinmanytaxa(fliesandvertebrates),butnotalltaxa

P.Z.Myers

EvolutionofHox clusters

• HOX-clustersundergoessentialrearrangementsinevolutionofmaintaxa

• Duplication,deletion,divergenceofthegenesleadtodifferentiationinbodyplans

• Otherregulatorygenes/genefamiliesarealsoimportant

Animalbodyplans

EvolutionarychangesinHox Genes

• Newmorphologicalformslikelycomefromgeneduplicationeventsthatproducenewdevelopmentalgenes

• Apossiblemechanismfortheevolutionofsix-leggedinsectsfromamany-leggedcrustaceanancestorhasbeendemonstratedinlabexperiments

• SpecificchangesintheUbxgenehavebeenidentifiedthatcan“turnoff”legdevelopment

Hox gene6 Hox gene7 Hox gene8

About400mya

Drosophila Artemia

Ubx

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Differences in Hox gene expression distinguish the various arthropod segmentation patterns

• EvolutionofvertebratesfrominvertebrateanimalswasassociatedwithalterationsinHox genes

• TwoduplicationsofHox genes arethoughttohaveoccurredinthevertebratelineage

• Theseduplicationsmayhavebeenimportantintheevolutionofnewvertebratecharacteristics

EvolutionofVertebrates(PhylumChordata) • Polyploidizationisprobablythesinglemostimportantmechanismfortheevolutionofmajorlineagesandforspeciationinplants

Multipleroundsofpolyploidization mighthaveoccurredduringtheearlyevolutionofvertebrates

Vertebrates(withjaws)withfourHox clusters

Hypotheticalearlyvertebrates(jawless)withtwoHox clusters

Hypotheticalvertebrateancestor(invertebrate)withasingleHox cluster

SecondHoxduplication

FirstHoxduplication

4.DifferentiationGeneBatteries:

Consistofgroupsoffunctionallylinkedprotein-codinggenesundercommonregulatorycontrol,theproductsofwhichexecutecelltype–specificfunctionsandaremajordeterminantofcellspecializationinmetazoans

Theyareexpressedinthefinalstagesofgivendevelopmentalprocesses.

DifferentHierarchicalComponentsofGeneRegulatoryNetworks

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4.DifferentiationGeneBatteries: Consistofgroupsoffunctionallylinkedprotein-codinggenesundercommonregulatorycontrol,theproductsofwhichexecutecelltype–specificfunctionsandaremajordeterminantofcellspecializationinmetazoans

• ResideattheperipheryofdevelopmentalGRNs,andareexpressedinthefinalstagesofgivendevelopmentalprocesses

• Theydonotregulateothergenes(incontrasttokernelsandplug-ins,whichareentirelyregulatory)

• Theydonotcontroltheprogressiveformationofspatialpatternsofgeneexpressionthatunderliesthebuildingofthebodyplan;inshort,theydonotmakebodyparts.

• Differentiationgenebatteriesbuildmusclecellsandmakeskeletalbiominerals,skin,synaptictransmissionsystems,etc.

DifferentHierarchicalComponentsofGeneRegulatoryNetworks

So....Kernelsofthenetwork:• Kernelsspecifythedomainforeachbodypartinthespatial

coordinatesystemofthepostgastrular embryo•• Highlypleiotropically constrained

o internalrecursivewiring—manylinkageso positionhighinthedevelopmentalnetworkhierarchy

Whensufficientcomparativenetworkdataareavailable,itislikelythatconservednetworkkernelswillbefoundtoprogramtheinitialstagesofdevelopmentofeveryphylum-specificbodypartandperhapsofsuperphylum andpan-bilaterian bodypartsaswell.

EvolutionwithinDevelopmentalGeneRegulatoryNetworks

Incontrast,peripheralregionsoftheGRN(i.e.differentiationgenebatteries)arelesspleiotropicallyconstrained,andmorelikelytoevolve.

Therearenodownstreamconsequencesinchangesatthislevel.

Examples:manycasesofspeciation,manycasesofadaptationtotheenvironment

EvolutionwithinDevelopmentalGeneRegulatoryNetworks

So,notallmutationsareequal:

Mutationsthatareretainedthataffecttheearlierstagesofdevelopment(e.g.kernels)willhavemoreprofoundeffectsonanimalbodyplansthanmutationsthataffecttheterminalstepsofdevelopment(e.g.genebatteries)

Sothen,whydidmassivediversificationofmajorbodyforms(evolutionarychangesinthepleiotropic kernels)occuratthetimeofthe“CambrianExplosion”

Andwhydidsuchchangesnotoccurafterthat?

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Thekernelswouldhaveformedthroughthesameprocessesofevolutionthataffecttheothercomponents(whilenewlineageswereformingduringthelatePre-Cambrian-earlyCambrian),

But,onceformedandoperatingtospecifyparticularbodyparts,kernelstructurewouldhavebecomerefractory(resistant)tosubsequentchange(becauseofthecatastrophiccostsofalteringfundamentalstructures—becausethedevelopmentalpathwayshadalreadybeenlaidout).

MolecularphylogenyplacesthisevolutionarystageinthelateNeoproterozoic whenBilateria begintoappearinthefossilrecord,betweentheendoftheMarinoan glaciation atabout630millionyearsagoandthebeginningoftheCambrian.

Thereforethemechanisticexplanationforthesurprisingfactthatessentiallynomajornewphylum-levelbodypartshaveevolvedsincetheCambrianmaylieintheinternalstructuralandfunctionalpropertiesofGRNkernels:Oncetheywereassembled,theycouldnotbedisassembledorbasicallyrewired,onlybuiltupon.

DiversekindsofchangeinGRNs andtheirdiverseevolutionaryconsequences

Fig.3.Theleftcolumnshowschangesinnetworkcomponents;therightcolumnshowsevolutionaryconsequencesexpected,whichdifferintheirtaxonomiclevel(red).

Bigphylogeny

“Kernals”

“GeneBatteries”

SampleExamQuestions

1. WhichofthefollowingisFALSE regardinghox Genes?(a)Theyservetheroleofdefiningsegmentalregionsalongtheanteriorto

posterioraxisduringdevelopment(b)Theirfunctionshavediversifiedthroughgeneduplicationsfollowedby

differentiation(e.g.subfunctionalization),leadingtodifferentiationofsegmentalregionsinanimals

(c)Theyencodetranscriptionfactorsthatperformtrans-regulatoryfunctions(d)Theyareresponsibleforthemajordifferencesamonganimalphyla(e)Theyfunctionbyallowingordisallowingdevelopmentalsubcircuits to

functionwithinsegmentalregions(likean"on/off"switch)

2. Whichofthefollowingwouldbemostevolutionaryconstrained?

(a)Plug-insoftheGRN(b)KernelsoftheGRN(c)Input/Outputdevices(d)Genebatteries(e)Hox genes

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3.Changesatwhichbelowaremostlikelytoberesponsiblefortheradiationofanimalphyla?

(a)Plug-insoftheGRN(b)SonicHedgehog(c)Input/Outputdevices(d)Genebatteries(e)KernelsoftheGRN

4.Whatarehox geneswithinanindividualanimal?

(a)Orthologs(b)Paralogs(c)Homologs(d)Xenologs(e)Noneoftheabove

5. Developmentalevolutionarydifferencesbetweenhumansandchimpanzeesaremostlikelytobeatthelevelof

(a)Plug-insoftheGRN(b)hox genes(c)Input/Outputdevices(d)Genebatteries(e)Kernels

• 1D• 2B• 3E• 4B• 5D

• OptionalSlides(foryourowninterest)

Differentsub-circuitswithinGeneRegulatoryNetworks

Don’tneedtoknowthis,justshowingasanexample

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Changesthatcanaffectcis-regulatorymodules(CRMs)(canreviewlecturenotesoncis-regulatoryevolution)

• Internalchangesthataffectthefunctionofapre-existingCRMo Singlebase-pairmutationcancausegainofnewbindingsites,lossofsites,orstrengtheningorweakeningofbindingtosites.

o Insertionsanddeletionscanchangethedistancebetweeninteractingsites,causegainorlossofsites,oranincreaseinthecopynumberofgivensites.

o Insertionofmobileelementcarryingregulatorysequencescancausegainorpotentiallossofsite,changeinthedistancebetweeninteractingsitesandincreaseincopynumber,aswellasalterthestrengthofbindingatthesite.

• ChangesthatalterCRMrepertoireofpre-existinggeneso InsertionofCRMs fromelsewhere:carriedbymobileelements,byinversions,bytranslocations,orbyintronic retrotranspositions cancausegainofdevelopmentalfunctionswithoutlossofthegene.

o LossofaCRM:bytranslocation,largedeletion,inversionbreakageorinsertionofmobileelementcancauselossofspecificdevelopmentalfunctionwithoutlossofgene.

• Large-scale rearrangements that produce novel gene–CRM complexeso Regionalduplicationscanresultinsubfunctionalization andneofunctionalization.o Translocationscanbringnewgenesintolargeregulatorydomains.