Download what can zebrafish tell us about human skin

WHATCANZEBRAFISHTELLUSABOUT
HUMANSKINCOLOR?
Educator Materials
OVERVIEW
InthefilmTheBiologyofSkinColor,Dr.NinaJablonskiproposedanexplanationforwhyhumansliving
indifferentpartsoftheworldhavedifferentnaturalskincolors.Specifically,studentslearnedhow
patternsinvariationfortheMC1Rgeneprovideevidencethatdarkskinisfavoredinenvironments
thatexperienceintenseUVradiation.Thisactivityfocusesonadifferentgene,SLC24A5,whichplaysa
largeroleintheexpressionoflighterskintonescommoninpeopleofEuropeandescent.Students
exploredatageneratedfromgeneticstudiesinfishtohelpthemunderstandthefunctionand
evolutionofSLC24A5.
KEYCONCEPTSANDLEARNINGOBJECTIVES
•
Studiesofmodelorganismscanprovidevaluableinformationaboutgenefunctioninhumans.
•
Changestoagene’sDNAsequencecanaffectthetranslationofthegeneintoaminoacids,
andultimately,thefunctionofaproteinandtheexpressionofatrait.
•
Geneticsandtheenvironmentcanaffectexpressionofatrait.Experimentssuggestthedegree
towhichdifferencesintraitsareinherited.Differencesinhumanskincoloraremostly
controlledbygenetics.
•
Bycomparinggenesandproteinsamongspecies,scientistscaninfercommonancestryand
whenagiventraitevolved.
•
Patternsinallelefrequenciesamongpopulationscanindicateadaptationandwhetheratrait
hasevolvedmorethanonce.
Studentswillbeableto
•
constructexplanations,makepredictions,andproposehypothesesbasedonavailable
information;and
•
userealdatapresentedinscientificfiguresandinformationfromthefilmtomakeevidencebasedclaims.
SUGGESTEDAUDIENCE
•
Thislessonisappropriateforalllevelsofhighschoolbiology,includingAPandIB,aswellas
introductorycollegebiology.
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WHATCANZEBRAFISHTELLUSABOUT
HUMANSKINCOLOR?
Educator Materials
CURRICULUMCONNECTIONS
Curriculum
Standards
NGSS(April2013)
Practices2,4,7;
HS-LS1-1,HS-LS3-3,HS-LS4-1
APBiology(2012–2013)
SciencePractices1,5;
1.A.2,1.A.4,3.A.1,3.C.1,4.C.2
IBBiology(2016)
3.1,5.1,5.2,7.2
KEYTERMS
adaptation,allele,allelefrequency,gene,melanin,melanosome,phenotype
TIMEREQUIREMENTS
Thislessonwasdesignedtobecompletedwithinasingle50-minuteclassperiodbutmaytakelonger
dependingontheamountofclassdiscussion.Thisdoesnotincludethenecessarytimetowatchthe
shortfilm.
PRIORKNOWLEDGE
•
StudentsshouldhaveabasicunderstandingofMendeliangenetics,includingthetermsDNA,gene,
andallele,andknowthatvariationsinsometraitsareinherited.
•
Itwouldbehelpfulforstudentstohavepriorknowledgeofthetermsgenotypeandphenotypeand
howtoapplythetermstospecificexamples.
•
Studentsneedabasicunderstandingofhowadaptationsarisethroughevolutionbynatural
selection.
TEACHINGTIPS
•
Havestudentswatchtheshort(19-minute)filmTheBiologyofSkinColorbeforecompletingthis
activity.Ifyoudon’thavesufficientin-classtime,considerassigningitforhomework.Have
studentswritedownanyquestionstheyhavewhiletheywatch.Runthroughsomeofthese
questionsasawarm-uporasaconcludingdiscussion.
•
Beforebeginningthelesson,considerreviewinggenesandalleleswithstudents.Onewayto
accomplishthisistoasktheminanopen-endedclassdiscussiontoeliciteverythingtheyknow
aboutgenesandalleles.Writeeverythingstudentssaysoallcanseethelist.Attheendofthe
brainstormingsession,highlightthefollowingoverarchingconcepts.
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WHATCANZEBRAFISHTELLUSABOUT
HUMANSKINCOLOR?
Educator Materials
o Genesareinherited.Genesarelocatedonchromosomes.Chromosomesareinheritedin
pairs,onefromeachparent.Differentversionsofgenesarecalledalleles.Asinglegenecan
havemanyalleles.
o Genesaffectphenotypes.Genescodeforproteins,whicharecriticalforthousandsof
functionswithincells.Theexpressionandactionofproteinsresultinthedistinguishable
traitsofanorganism:itsphenotypes.
•
Theactivityhasbeenconstructedtominimizecopiesandtopromoteactivelearning.For
implementation,consideraninterruptedapproachofinstructionorsmallteam-basedlearning
groups.Foradiscussion-basedapproach,figurescouldbeprojectedandstudentscouldbegiven
timetolookatthedataindividually,thenpairwithanotherstudent,andthenshareoutviawholegroupdiscussion.Anotherapproachcouldbetoprovidesmallgroupsoftwotofourstudentsa
singlesetofreferencefigures(recommendusingcardstockandlaminatingifpossiblesothe
referencesetscanbereused)andallowthemtohaveteam-baseddiscussionsaboutthedata.
•
Someofthedataconsideredinthisactivityistakenfromzebrafish.Forexample,studentsare
presentedresultsfromastudythattransplantedahumanskin-colorgeneintoazebrafish.Takethe
opportunitytoreinforcetheuniversalityofthegeneticcodeasevidenceforcommondescent.
•
Makesuretoemphasizethecriticalpointthatwhilemuchofthedataforskincolorpresentedin
thisactivityfocusesondifferencesamongpeople,mostoftheothergeneticdatashowhowclosely
relatedallhumansaretoeachotherandhowmuchpeoplehaveincommon.
•
Question4hasstudentsreflectingonwhetherallelefrequencydataisevidenceofselection,
specifically,that96percentofindigenousEuropeanshaveoneallelefortheskin-colorgene
SLC24A5,whileonly9percentofWestAfricansdo.Ifyourstudentsarefamiliarwithgenetics,you
maytellthemthatsimulationsusingmathematicalmodelsshowthatitishighlyimprobable(less
thana0.01percentchance)thatthesedifferencesinallelefrequencycouldhavearisenbygenetic
driftalone.
•
Figure4,referencedinquestion8,indicatesthatchimpanzeesandotheranimalsallhavetheG
alleleoftheSLC24A5gene,whichwouldsuggestthattheyhavehighlymelanizedskin—but
certainlynotallofthemdo(forexample,chimpanzeeshavepaleskinunderneaththeirdarkfur).If
itcomesup,pointouttostudentsthatonlyasmallportionoftheproteinisshownandother
variationsmayexist.Further,skincolorispolygenic,sovariationsinmanyothergenesmaybe
causingthedifferenceinskincolor,andtherecouldbeenvironmentaleffectsaswell.
•
Questions11through13areaboutdatacontainedintwodifferentmaps.Inquestion13,students
areaskedtosynthesizethetwomapstoevaluatetheclaimthatlight-skinnedphenotypesevolved
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WHATCANZEBRAFISHTELLUSABOUT
HUMANSKINCOLOR?
Educator Materials
onlyonceinhumanhistory.Studentsshouldconcludethattheclaimisnotsupportedbythedata,
butthatlight-skinnedphenotypesevolvedatleasttwice,onceamongEuropeansandonceamong
Asians.
VarioushumanpopulationsdispersedfromAfricainwaves.Forexample,somehumansmigrated
outofAfricaandwenttoAsiaabout35,000yearsagoandevolvedlessmelanizedskininresponse
tolowerlevelsofUVradiation.AdifferentgroupofhumanssettledinEuropeabout40,000years
agoandalsoevolvedlessmelanizedskin.Thus,bothpopulationsevolvedsimilartraits(less
melanizedskin)inresponsetoasimilarenvironmentalinfluence.
BoththeEuropeanandAsiandispersalstookplacelessthan50,000yearsago.Bothpopulations
camefromancestorsinAfrica.Thus,themovenorthinfluencednaturalselectiononbothEuropean
andAsianpopulationsinarelativelyshortamountoftime.IntheEuropeanpopulation,theGallele
ofSLC24A5wasstronglyselectedagainst,resultinginselectionoftheAalleleandlesspigmentin
skin.BecausethisalleleremainsinhighfrequencyinAsianpopulations,someothergeneorgenes
mustberesponsibleforthelowermelanincontentinAsianskin.EvidencefromtheOCA2Gallele
frequencysupportsthisclaimbecauseitisassociatedwithlighterskinbutisessentiallyrestricted
toindividualsindigenoustoEastAsia,orofEastAsianancestry.
ANSWERKEY
1. Thecells(melanophores)inthewild-typezebrafisharelargerandcontainlargerandmore
abundantmelanosomesandmuchmoremelanincomparedtothemelanophoresofthegolden
zebrafish.
2. Answersmayvary.Anacceptableanswerwouldbethatthemelanincolorinthegolden
zebrafishmelanosomeslookslikethemelaninfromthewomanwithlightskin.
3. TheimagesinFigure2showthatthesizeandnumberofmelanosomes,andtheamountof
melanin,aredifferentinpeoplewithdifferentskincolors.Remindstudentsthatthefilm
mentionedthataperson’sskincolorisdeterminedbythetypeandamountofmelaninintheir
skin.“Thereddish-yellowpheomelaninismoreabundantinlightlypigmentedpeople.More
darklypigmentedpeoplehavemoreofthebrown-blackeumelanin,andthemoreeumelanin,
thedarkertheskin.”
4. DNAcodesforamessengerRNA(mRNA),whichcanbetranslatedintoaprotein.ThemRNAis
readingroupsofthreetocodeforaspecificaminoacid.AchangeinaDNAsequencewill
changethemRNAthatgetsformed,whichcouldresultinacodeforadifferentaminoacidand
ultimatelyadifferentprotein.
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WHATCANZEBRAFISHTELLUSABOUT
HUMANSKINCOLOR?
Educator Materials
5. Yes.ThedifferencesinallelefrequencyfortheSLC24A5AallelearesodramaticbetweenWest
Africans(0.09)andEuropeans(0.96)thatselectionmustbeatplay.AlmostallEuropeanshave
theAallele,whileitisextremelyrareamongWestAfricans.ThisisverysimilartotheMC1R
variationseen(ornotseen!)amongindividualsinthesepopulations,whichwascausedby
selection.
6. Sampleanswer:Notreally;althoughpeoplewhoarehomozygousfortheGallelehavethe
highestamountofmelaninandthedarkestskincolorandpeoplewhoarehomozygousforthe
Aallelehavethelowestamountofmelaninandthelightestskincolor,thereisalargeamount
ofoverlapamongthegroups.SomeonewithaΔmelaninindexvalueof0,forexample,could
belongtoanyofthethreegenotypes.
7. a.othergenesandenvironmentalfactors
b.Thereissignificantoverlapamongthegroups.Ifitaccountedforallofthedifferences,then
therewouldbenooverlapatall;eachgenotypewouldresultinauniquephenotype.
8. Thehighdegreeofsimilarityinsequencessuggeststhattheproteinshaveasimilarfunction
acrossthedifferentspecies,andthisfunctioniscriticalforsurvivaland/orreproduction.The
simplestexplanationforthesimilarityinthesequencesisthatthegenewasinheritedfroma
commonancestorinallthespecies.
9. ThefactthatthemessengerRNA(mRNA)fromthehumanSLC24A5generestoredthehigh
melaninlevels(anddarkcolor)inthezebrafishlarvaestronglysuggeststhattheproteinshavea
similarfunctioninthedifferentspecies.
10. Thegenemusthaveevolvedinthemostrecentcommonancestorofallthegroupsonthetree,
whichexistedatleast400millionyearsago.Asaresult,thegenemusthavebeenpresentat
least400millionyearsago(thoughitmaybemucholder).
11. Asia,NorthernNorthAmerica,Australia,Europe,SouthernSouthAmerica.Thesearetheareas
withthelightestnativeskintones.
12.Answerswillvary,butmoststudentswillnoticethatEuropehasahighfrequencyoftheAallele
butAsiadoesnot;thiswillnotmatchtheirpredictions.
13.Thedatacontradicttheclaimbecauseclearlythereismorethanone“way”togetlightskin.
TheAalleleevolvedandspreadamongEuropeanpopulations,butnotinAsianpopulations,so
someothergeneticpathwayforforminglightskinmusthaveevolved.
14.Answerswillvary,butstudentsshouldmentionforexamplethatFigure4showsthatzebrafish
andhumansshareacommongeneticcodeandaremadeupofthesameconservedaminoacid
sequences.InFigure5,scientistswereabletotakeamessengerRNA(mRNA)fragmentfrom
thehumanDNAsequencefortheSLC24A5Galleleandinjectitintogoldenzebrafishembryos
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WHATCANZEBRAFISHTELLUSABOUT
HUMANSKINCOLOR?
Educator Materials
andthezebrafishwasabletotranslatethehumanmRNAintoaprotein.Thecladogramin
Figure6showsthatzebrafishandhumansshareacommonancestry.
REFERENCES
ThisactivityisadaptedfromanactivityintheEvolutionofHumanSkinColorcurriculumunitforAP
BiologythatisapartoftheSmithsonianInstitution’sNationalScienceFoundation-fundedTeaching
EvolutionthroughHumanExamplesproject(GrantNo.1119468).See
http://humanorigins.si.edu/education/teaching-evolution-through-human-examplestoexplorethefull
curriculumunit.
KlugW.S.,CummingsM.R.,SpencerC.A.(2006).ConceptsofGenetics.Pearson:NY.
LamasonR.L.,MohideenM.-A.P.K.,MestJ.R.,WongA.C.,NortonH.L.,ArosM.C.,JurynecM.J.,MaoX.,
HumphrevilleV.R.,HumbertJ.E.,SinhaS.,MooreJ.L.,JagadeeswaranP.,ZhaoW.,NingG.,Makalowska
I.,McKeigueP.M.,O’donnellD.,KittlesR.,ParraE.J.,ManginiN.J.,GrunwaldD.J.,ShriverM.D.,Canfield
V.A.,ChengK.C.(2005).SLC24A5,aputativecationexchanger,affectspigmentationinzebrafishand
humans.Science310(5755):1782–1786.
Norton,H.L.,Kittles,R.A.,Parra,E.,McKeigue,P.,Mao,X.,Cheng,K.,Canfield,V.A.,Bradley,D.G.,
McEvoy,B.andShriver,M.D.GeneticEvidencefortheConvergentEvolutionofLightSkininEuropeans
andEastAsians.(2007).Mol.Biol.Evol.24(3):710–722.
SturmR.A.,DuffyD.L.(2012).Humanpigmentationgenesunderenvironmentalselection.Genome
Biology13(9):248.doi:10.1186/gb-2012-13-9-248.
AUTHORS
WrittenbyPaulBeardsley,CaliforniaStatePolytechnicUniversity.EditedbyK.DavidPinkerton,
consultant;MelissaCsikari,HHMI;andStephanieKeep,consultant.CopyeditedbyLindaFelaco.
SCIENTIFICREVIEWERS
VinceBuonaccorsi,JuniataCollege;andRebeccaLamason,UniversityofCalifornia,Berkeley.
www.BioInteractive.org
PublishedAugust2016
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