The making of the Fittest: Natural Selection and Adaptation

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    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation

    Lesson The Making of the Fittest Natural Selection and Adaptation Educator Materials

    PublishedFebruary,2017

    Page1of8

    INTRODUCTIONTOTHEMOLECULARGENETICSOFTHECOLORMUTATIONSINROCKPOCKETMICE

    OVERVIEWTheselessonsserveasanextensiontotheHowardHughesMedicalInstituteshortfilmTheMakingoftheFittest:NaturalSelectionandAdaptation.Studentswilltranscribeandtranslateportionsofthewild-typeandmutantrockpocketmouseMc1rgene.BycomparingDNAsequences,studentsidentifythelocationsandtypesofmutationsresponsibleforthecoat-colorchangedescribedinthefilm.StudentswillansweraseriesofquestionstoexplainhowachangeinaminoacidsequenceaffectsthefunctionalityoftheMC1Rprotein,andhowthatchangemightdirectlyaffectthecoatcoloroftherockpocketmousepopulationsandthesurvivalofthatpopulation.KEYCONCEPTSANDLEARNINGOBJECTIVES

    AmutationisarandomchangetoanorganismsDNAsequence. Mostmutationshavenoeffectontraits,butsomemutationsaffecttheexpressionofageneand/orthe

    geneproduct. Theenvironmentcontributestodeterminingwhetheramutationisadvantageous,deleterious,orneutral. Naturalselectionpreservesfavorabletraits. Variation,selection,andtimefueltheprocessofevolution. Boththetypeofthemutationanditslocationdeterminewhetherornotitwillhaveaneffecton

    phenotype(advancedversiononly).Studentswillbeableto:

    transcribeandtranslateaDNAsequence. connectDNAchangestophenotype. analyzeandorganizedata.

    CURRICULUMCONNECTIONSCurriculum StandardsNGSS(April2013) HS-LS1-1,HS-LS3-1,HS-LS3-2,HS-LS4-2,HS-LS4-4,HS-LS4-5

    HS.LS1.A,HS.LS4.B,HS.LS4.CCommonCore(2010) CCSS.ELA-Literacy.RST.9-10.3,CCSS.ELA-Literacy.RST.9-10.4,

    CCSS.ELA-Literacy.RST.9-10.7APBiology(201213) 1.A.1,1.A.2,3.A.1,3.C.1,4.B.1IBBiology(2009) 3.5,4.1,4.3,5.4,7.3,7.4,D.2,G.1

    KEYTERMSevolution,naturalselection,variation,trait,mutation,adaptationTIMEREQUIREMENTTheseactivitiesaredesignedforone50-minuteclassperiodincludingshowingthefilm.Additionaltimefortheanalysisquestionsmightberequiredforhomeworkdependingonstudentspace.Bothactivitiescoverthesamematerial,butactivity2hasadditionalmaterialcoveringintracellular,transmembrane,andextracellulardomains.

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    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation Educator Materials

    Lesson The Making of the Fittest Natural Selection and Adaptation

    PublishedFebruary,2017Page2of8

    SUGGESTEDAUDIENCEActivity1:Theactivityisdesignedforhighschoolbiology(primarilyfirst-yearbiology,bothregularandhonors).Activity2:TheactivityisdesignedforAPandIBhighschoolbiologyandintroductorycollegebiology.PRIORKNOWLEDGEStudentsshouldbefamiliarwiththedefinitionsofgeneandprotein.Theyshouldalsobecomfortablewithbasicmoleculargenetics,includingafamiliaritywiththeprocessesoftranscriptionandtranslation.Finally,studentsshouldunderstandthataproteinsaminoacidsequencedeterminesitsstructure,whichdeterminesitsfunction.MATERIALSStudentswillneed:geneticcodechart(providedinstudentmaterials)blue,red,andgreencoloredpencilsTEACHINGTIPS

    Ifyoudonothaveaccesstoacolorprintertoprintthechartonpage2ofthisdocument,youshouldcomparestudentsworktohowthechartsbelowappearonyourcomputerscreen.

    Youcouldassignanalysisquestionsashomeworktoreducetheamountofclasstimerequiredforthislesson.

    ANSWERKEYACTIVITY1GENETABLE1:WILD-TYPEMC1RGENE(LIGHTCOAT-COLORPHENOTYPE)

    015 022DNA TTG AGG TGG GCG TGT CCG CAA GGAmRNA AAC UCC ACC CGC ACA GGC GUU CCUAminoAcid Asn Ser Thr Arg Thr Gly Val Pro

    105 112

    DNA CGG GAC CGG TGG GCC CAC TGA CACmRNA GCC CUG GCC ACC CGG GUG ACU GUGAminoAcid Ala Leu Ala Thr Arg Val Thr Val

    154 161

    DNA TCA TAA CAC TGT GAC GGG GCC CGAmRNA AGU AUU GUG ACA CUG CCC CGG GCUAminoAcid Ser Ile Val Thr Leu Pro Arg Ala

    209 212

    DNA GTG TAC GAA CGTmRNA CAC AUG CUU GCAAminoAcid His Met Leu Ala

  • www.BioInteractive.org

    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation Educator Materials

    Lesson The Making of the Fittest Natural Selection and Adaptation

    PublishedFebruary,2017Page3of8

    230 237

    DNA GAA CAG GTG GTT CCA AAG GCT GAGmRNA CUU GUC CAC CAA GGU UUC CGA CUCAminoAcid Leu Val His Gln Gly Phe Arg Leu

    GENETABLE2:MUTANTMC1RGENE(DARKCOAT-COLORPHENOTYPE)

    015 022DNA TTG AGG TGG ACG TGT CCG CAA GGAmRNA AAC UCC ACC UGC ACA GGC GUU CCUAminoAcid Asn Ser Thr Cys Thr Gly Val Pro

    105 112DNA CGG GAC CGG TGG ACC CAC TGA CACmRNA GCC CUG GCC ACC UGG GUG ACU GUGAminoAcid Ala Leu Ala Thr Trp Val Thr Val

    154 161

    DNA TCA TAA CAC TGT GAC GGG ACC CGAmRNA AGU AUU GUG ACA CUG CCC UGG GCUAminoAcid Ser Ile Val Thr Leu Pro Trp Ala

    209 212

    DNA GTG TAC GAG CGTmRNA CAC AUG CUC GCAAminoAcid His Met Leu Ala

    230

    237

    DNA GAA CAG GTG GTG CCA AAG GCT GAGmRNA CUU GUC CAC CAC GGU UUC CGA CUCAminoAcid Leu Val His His Gly Phe Arg Leu

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    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation Educator Materials

    Lesson The Making of the Fittest Natural Selection and Adaptation

    PublishedFebruary,2017Page4of8

    QUESTIONSANSWERKEY1.Ingeneexpression,whichenzymeisresponsiblefortranscribingtheDNAsequenceintomRNAbyaddingcomplementaryRNAnucleotides?RNApolymerase2.Inaeukaryoticcell,wheredoestranscriptionoccur?Inthenucleus3.Describetheprocessoftranslation.TranslationistheprocessofturninginstructionsfrommRNAintochainsofaminoacids.ItoccursinthecytoplasmwiththehelpofribosomesandtRNA.4.Inaeukaryoticcell,whatmainorganelleisinvolvedintranslation?Ribosome5.ExplaintherelationshipbetweenDNAsequence,aminoacidsequence,andproteinstructureandfunction.StudentsmaysimplyrelateDNAsequencetoaminoacidsequence,andaminoacidsequencetothethree-dimensionalshapeoftheprotein.Anexampleofastudentresponsemaybe:DNAsequenceprovidesthecodefortheaminoacidsequence.Theaminoacidsequencedeterminesthestructureoftheprotein,whichaffectsthefunctionoftheprotein.6.TheMc1rgenecodesforthemelanocortin1receptor(MC1R)protein.7.IftheMC1Rproteinis317aminoacidslong,whyarethere954basepairsinthecodingregionofthegene?EachoftheaminoacidshasacorrespondingmRNAcodonandDNAtripletconsistingofathree-basesequence.Aproteinthathas317aminoacidsthereforehasaDNAbasesequenceconsistingof951basepairs(3173=951basepairs).Thethreeadditionalbasepairscorrespondtoastopcodonforwhichthereisnocomplementaryaminoacid.Thestopcodonsignalstheterminationoftranslation.8.OfthefivemutationsyouidentifiedintheMc1rgene,howmanyare: 5substitutions;0insertions;0deletions9.OfthefivemutationsyouidentifiedintheMc1rgene,howmanyare: 1silent;4missense;0nonsense10.Micewiththewild-type(nonmutant)Mc1rgenehavelight-coloredfur.Whichpigmentisresponsibleforthiscoloration?Pheomelanin11.Usingtheinformationintheintroductiononmutationsandyourknowledgeofproteins,developahypothesistoexplainhowthechangesintheMC1Rproteinsaminoacidsequencemightaffectitsfunction.Sampleanswer:ThefourmissensemutationsintheMc1rgenechangetheaminoacidsequenceoftheMC1Rprotein,whichchangesthestructureoftheprotein.Thechangeinproteinstructurewillaffecttheproteinfunction.12.Explainhowsilentmutationsaffectthestructureandfunctionoftheprotein.Silentmutationsdonotchangetheaminoacid,andthereforewillnotchangethestructureoftheprotein.Becauseaproteinsstructureisrelatedtoitsfunction,silentmutationsdonotaffectthefunctionoftheprotein.13.UsingtheinformationprovidedintheintroductionunderMC1RGene,explainhowthemutantMC1Rproteindirectlyaffectsarockpocketmousescoatcolor.TheaminoacidchangesintheMC1Rproteinmaychangethestructureandfunctionoftheprotein.Thisleadstoincreasedproductionofeumelanin,whichresultsinthedarkcolor.14.Mutationsareasourceofgeneticvariation.Inthefilm,Dr.Carrollsaysthatmutationsoccurrandomly.Whatdoesthatmean?Sampleanswer:Itmeansthatmutationsdonotoccurforapurposeorforanypredeterminedresult.15.Itisacommonmisconceptionthatallmutationsarebad.Usetheexampleofrockpocketmicetoexplainwhythisisnottrue.Inyouranswer,explainhowthedarkcoatcolormutationcanbeanadvantagetosomemiceandadisadvantagetoothers.Sampleanswer:Mutationscanresultinnewtraits.Theselectiveadvantageprovidedbyatraitdependsontheenvironment.Forexample,onalightsubstrate,individualswithdark-coloredcoatswouldbeatadisadvantage

  • www.BioInteractive.org

    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation Educator Materials

    Lesson The Making of the Fittest Natural Selection and Adaptation

    PublishedFebruary,2017Page5of8

    becausetheywouldstandoutmorethanindividualswithlight-coloredcoats,makingthemeasierforpredatorstospot.However,inthedarklavaflowhabitat,thosesamedark-coloredindividualswouldhaveaselectiveadvantagebecausetheywouldbebettercamouflagedthanlight-coloredindividuals.So,thestatementthatallmutationsarebadisincorrect,becausetherearedifferentselectivepressuresonthetraitsproducedbymutationsdependingonthehabitat.Therearealsosilentmutationsthatdonotchangetheresultingprotein;theseareneutral,neithergoodnorbad.16.Useyourunderstandingofevolutionandtheinformationinthefilmtoexplainhowthedark-coloredmutationcametobesocommoninsomepopulationsofrockpocketmice.Bespecific.Sampleanswer:Thedark-coloredmousehasaselectiveadvantageinahabitatsuchasthePinacatelavaflow,whichhasadark-coloredsubstrate.Sincerockpocketmicereproducequicklyandoften,thefrequencyofthisfavoredtraitwouldspreadrapidlythroughthepopulation.Anylight-coloredmiceinthedark-coloredhabitatwouldbeataselectivedisadvantage,thusdecreasingtheirgenefrequencyinfuturegenerations.Inthisway,favorabletraitsaccumulateandincreaseinfrequencyjustasDarwinexplained.ANSWERKEYACTIVITY2

    GENETABLES

    WILD-TYPEMC1RGENE(LIGHT-COLOREDCOATPHENOTYPE) 015 024

    DNA TTG AGG TGG GCG TGT CCG CAA GGA GTG GAG

    EXTR

    ACELLU

    LARDO

    MAINI

    mRNA AAC UCC ACC CGC ACA GGC GUU CCU CAC CUCAminoAcid Asn Ser Thr Arg Thr Gly Val Pro His Leu

    MUTANTMC1RGENE(DARK-COLOREDCOATPHENOTYPE) 015 024

    DNA TTG AGG TGG ACG TGT CCG CAA GGA GTG GAGmRNA AAC UCC ACC UGC ACA GGC GUU CCU CAC CUCAminoAcid Asn Ser Thr Cys Thr Gly Val Pro His Leu

    WILD-TYPEMC1RGENE(LIGHT-COLOREDCOATPHENOTYPE) 105 114

    DNA CGG GAC CGG TGG GCC CAC TGA CAC CAT GTC

    EXTR

    ACELLU

    LARDO

    MAINIII

    mRNA GCC CUG GCC ACC CGG GUG ACU GUG GUA CAG

    AminoAcid Ala Leu Ala Thr Arg Val Thr Val Val Gln

    MUTANTMC1RGENE(DARK-COLOREDCOATPHENOTYPE) 105 114

    DNA CGG GAC CGG TGG ACC CAC TGA CAC CAT GTCmRNA GCC CUG GCC ACC UGG GUG ACU GUG GUA CAGAminoAcid Ala Leu Ala Thr Trp Val Thr Val Val Gln

  • www.BioInteractive.org

    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation Educator Materials

    Lesson The Making of the Fittest Natural Selection and Adaptation

    PublishedFebruary,2017Page6of8

    WILD-TYPEMC1RGENE(LIGHT-COLOREDCOATPHENOTYPE) 154 163

    DNA TCA TAA CAC TGT GAC GGG GCC CGA GCC ACC

    INTR

    ACELLU

    LARDO

    MAINI

    mRNA AGU AUU GUG ACA CUG CCC CGG GCU CGG UGGAminoAcid Ser Ile Val Thr Leu Pro Arg Ala Arg Trp

    MUTANTMC1RGENE(DARK-COLOREDCOATPHENOTYPE) 154 163

    DNA TCA TAA CAC TGT GAC GGG ACC CGA GCC ACCmRNA AGU AUU GUG ACA CUG CCC UGG GCU CGG UGGAminoAcid Ser Ile Val Thr Leu Pro Trp Ala Arg Trp

    WILD-TYPEMC1RGENE(LIGHT-COLOREDCOATPHENOTYPE) 208 212

    DNA CAC GTG TAC GAA CGTTR

    ANSM

    EMBR

    ANEV

    mRNA GUG CAC AUG CUU GCAAminoAcid Val His Met Leu Ala

    MUTANTMC1RGENE(DARK-COLOREDCOATPHENOTYPE)

    208 212DNA CAC GTG TAC GAG CGTmRNA GUG CAC AUG CUC GCAAminoAcid Val His Met Leu Ala

    WILD-TYPEMC1RGENE(LIGHT-COLOREDCOATPHENOTYPE) 230 239

    DNA GAA CAG GTG GTT CCA AAG GCT GAG TTT CCGINTR

    ACELLU

    LARDO

    MAINIII

    mRNA CUU GUC CAC CAA GGU UUC CGA CUC AAA GGCAminoAcid Leu Val His Gln Gly Phe Arg Leu Lys Gly

    MUTANTMC1RGENE(DARK-COLOREDCOATPHENOTYPE) 230 239

    DNA GAA CAG GTG GTG CCA AAG GCT GAG TTT CCGmRNA CUU GUC CAC CAC GGU UUC CGA CUC AAA GGCAminoAcid Leu Val His His Gly Phe Arg Leu Lys Gly

  • www.BioInteractive.org

    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation Educator Materials

    Lesson The Making of the Fittest Natural Selection and Adaptation

    PublishedFebruary,2017Page7of8

    QUESTIONSANSWERKEY1.Usingtheaminoacidlocationnumbersprovidedabovethefirstandlastcolumnofeachtable,listthelocationsofthefiveaminoacidsthatcontainamutation.Theaminoacidlocationsare018,109,160,211,and233.2.OfthefivemutationsyouidentifiedintheMc1rgene,howmanyarethefollowing: 5substitutions,0insertions,0deletions3.OfthefivemutationsyouidentifiedintheMc1rgene,howmanyarethefollowing: 1silent,4missense,0nonsense4. a.Whichfouraminoacidlocations(seeQuestion1above)containthemissensemutations?Theaminoacidsare018,109,160,and233.b.ExplainthelinkbetweenDNAsequenceandproteinstructureandfunction.StudentsmaysimplyrelateDNAsequencetoaminoacidsequence,andaminoacidsequencetothethree-dimensionalshapeoftheprotein.More-advancedstudentsshouldbeabletolinkthemutationtoachangeintheproteinsprimarystructure,whichaffectsotherlevelsofstructure(secondaryandtertiary).AllstudentresponsesshoulddemonstrateanunderstandingofthelinkbetweenDNAandthesequenceofaminoacidsthatdeterminesthestructure,andthereforefunction,ofaprotein.5.Usingtheinformationonmutationsintheintroductionandyourknowledgeofproteins,developahypothesistoexplainhowthechangesintheMC1Rproteinsaminoacidsequencemightaffectitsfunction.StudentsmightsuggestthatsincethefourmissensemutationsintheMc1rgenechangetheaminoacidsequenceoftheMC1Rprotein,theproteinwillnotfunctionproperly,asaproteinsfunctionisdeterminedbyitsstructure.6.Manyproteins,includingMC1R,containseveralstructuraldomainsthatcanfoldandfunctionindependentlyfromtherest.ThedomainnameswereprovidedforeachportionofDNAsequenceyoutranslatedearlier.Answerthefollowingquestions.a.WhereistheMC1Rproteinfound,andwhatisitsfunction?Bespecific.Itisareceptorproteinembeddedinthemembraneofmelanocytes.Itisspecializedforpigmentproduction.b.WhichproteindomainscontainthefourMc1rmissensemutations?(Refertothegenetablesyoucompletedearlier.)Themutationat018isinExtracellularDomainI,themutationat109isinExtracellularDomainIII,themutationat160isinIntracellularDomainI,andthemutationat233isinIntracellularDomainIII.c.Defineextracellular.Extracellularmeanssomethingoutsideofacell.d.Defineintracellular.Intracellularmeanssomethinginsideofacell.e.Whyisitsignificantthatthefourmissensemutationsarefoundintheextracellularandintracellulardomainsoftheprotein?Explainyouranswer.(Hint:ThinkaboutMC1Rsfunction.)Specificanswerswillvary,butstudentsshouldhavetheideathataproteinthatspansacellmembranehasaportionthatprojectsoutofthecell(extracellular)andaportionthatprojectsintothecell(intracellular).Thistypeofreceptorproteinusuallyfunctionsineithercelltransportorcellsignaling.Changesinthestructureofextracellularandintracellularportionscanchangethefunctionoftheproteininthesignalingpathwayorthetransportmechanism.(Note:SeethelessonTheBiochemistryandCellSignalingPathwayoftheMc1rGeneformoredetailonthisconcept.)

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    LESSONTEACHERMATERIALS

    The Making of the Fittest: Natural Selection and Adaptation Educator Materials

    Lesson The Making of the Fittest Natural Selection and Adaptation

    PublishedFebruary,2017Page8of8

    7.UsingtheinformationontheMc1rgeneintheintroductionandyourknowledgeofproteins,developahypothesistoexplainhowthechangeinMC1Rproteinfunctionmightdirectlyaffectarockpocketmousescoatcolor.Bespecificandconsiderboththelight-coloredanddark-coloredphenotypes.Specificanswerswillvary,butstudentsshouldsuggestthatthenormalMC1Rreceptorproteinwillproducerelativeamountsofeumelaninandpheomelaninthatwillresultinthelightcoatcolor.Inaddition,thedark-coloredmousepopulationcontainsthemutantMc1rgene,whichresultsinadifferentreceptorprotein.Thischangeinstructuremightleadtoincreasedproductionofeumelanin,whichresultsinthedarkcolor.8.Explainwhythemutationataminoacidlocation211isnotassignificantastheotherfourmutations.Itisasilentmutation,sotheaminoacidinthatpositiondoesnotchange,nordoesthestructureofthespecificdomain.Thisisimportantbecauseaproteinsstructurerelatestoitsfunction.Nochangeinthestructuresuggeststhatthereisnochangeinthefunctionofthisparticulardomainoftheprotein.9.Mutationsareasourceofgeneticvariation.Inthefilm,Dr.SeanCarrollsaysthatmutationsoccurrandomly.Whatdoesthismean?Sampleanswer:Itmeansthatmutationsdonotoccurforapurposeorforanypredeterminedresult.10.Itisacommonmisconceptionthatallmutationsarebad.Usetheexampleofrockpocketmicetoexplainwhythisstatementisnottrue.Inyouranswer,explainhowthedarkcoat-colormutationcanbeanadvantagetosomemiceandadisadvantagetoothers.Sampleanswer:Mutationscanresultinnewtraits.Theselectiveadvantageprovidedbyatraitdependsontheenvironment.Forexample,onalightsubstrate,individualswithdark-coloredcoatswouldbeatadisadvantagebecausetheywouldstandoutmorethanindividualswithlight-coloredcoats,makingthemeasierforpredatorstospot.However,inthedarklavaflowhabitat,thosesamedark-coloredindividualswouldhaveaselectiveadvantagebecausetheywouldbebettercamouflagedthanlight-coloredindividuals.Sothestatementthatallmutationsarebadisincorrect,becausetherearedifferentselectivepressuresonthetraitsproducedbymutationsdependingonthehabitat.Therearealsosilentmutationsthatdonotchangetheresultingprotein;theseareneutral,neithergoodnorbad.11.Useyourunderstandingofevolutionandtheinformationinthefilmtoexplainhowthedark-coloredmutationcametobesocommoninsomepopulationsofrockpocketmice.Bespecific.Sampleanswer:Thedark-coloredmousehasaselectiveadvantageinahabitatsuchasthePinacatelavaflow,whichhasadark-coloredsubstrate.Sincerockpocketmicereproducequicklyandoften,thefrequencyofthisfavoredtraitwouldspreadrapidlythroughthepopulation.Anylight-coloredmiceinthedark-coloredhabitatwouldbeataselectivedisadvantage,thusdecreasingtheirgenefrequencyinfuturegenerations.Inthisway,favorabletraitsaccumulateandincreaseinfrequencyjustasCharlesDarwinexplained.AUTHORAnnBrokawAPBiologyTeacherRockyRiverHighSchoolRockyRiver,Ohio

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