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CHAPTERNINE VISION OnlyonceinmyentirecareerhaveIfoundtheeyeofa fossilcreature.Iwasn’tinthefieldonanexpedition,Iwas inthebackroomofamineralshopinasmalltownin northeastChina.MycolleagueGaoKeqinandIwere studyingtheearliestknownsalamanders,beautifulfossils collectedfromChineserocksabout160millionyearsold. WehadjustfinishedacollectingtriptosomesitesGao knewabout.Thelocationsweresecret,becausethese salamanderfossilshaveseriousmonetaryvalueforthe farmerswhotypicallyfindthem.Whatmakesthemspecial isthatimpressionsofthesofttissue,suchasgills,guts,and thenotochord,areoftenpreserved.Privatecollectorslove thembecausefossilsofthisqualityareexceedinglyrare.By thetimeweendedupatthemineralshop,GaoandIhad alreadycollectedanumberofreallybeautifulancient salamandersofourownfromhissites. Thisparticularmineraldealerhadgottenhishandson oneofthebestsalamanderfossilsofalltime.Gaowantedus toseeitandspentthebetterpartofadaytryingtowork 197 thedeal.Thewholevisithadaterrificallyillicitfeel.Gao spentseveralhourssmokingcigaretteswiththegentleman, speakingandgesturinginChinese.Clearlytherewassome barteringgoingon,butnotknowingChineseIhadnoidea whatofferswerebeingputonthetable.Afterlotsof headshakingandultimatelyabighandshake,Iwas permittedtogotothebackroomandlookatafossilonthe dealer’sdesk.Itwasastunningsight:thebodyofalarval salamander,nomorethanthreeincheslong.Init,Icould seeimpressionsofthewholeanimal,allthewaydownto thelittleshellsitateasitslastmeal.And,forthefirstand onlytimeinmycareer,Iwasstaringattheeyeofanancient fossilanimal. Eyesrarelymakeitintothefossilrecord.Aswe’veseen, thebestcandidatesforpreservationasfossilsarethehard partsoftheanimals—bones,teeth,andscales.Ifwewantto understandthehistoryofeyes,thenwecanusean importantfacttoouradvantage.Thereisaremarkable diversityoforgansandtissuesthatanimalsusetocapture light,fromsimplephotoreceptororgansininvertebrate animalstothecompoundeyesofvariousinsectsandour owncamera-typeeye.Howdoweputthisvariationtouse inunderstandinghowourabilitytoseedevelopedover time? Thehistoryofoureyesisalotlikethatofacar.Takea ChevyCorvette,forexample.Wecantracethehistoryofthe modelasawhole—theCorvette—andthehistoryofeachof itsparts.The’Vettehasahistory,beginningwithitsorigins 198 in1953andcontinuingthroughthedifferentmodeldesigns eachyear.Thetiresusedonthe’Vettealsohaveahistory, asdoestherubberusedinmakingthem.Thissuppliesa greatanalogyforbodiesandorgans.Oureyeshavea historyasorgans,butsodoeyes’constituentparts,thecells andtissues,andsodothegenesthatmakethoseparts. Onceweidentifythesemultiplelayersofhistoryinour organs,weunderstandthatwearesimplyamosaicofbits andpiecesfoundinvirtuallyeverythingelseontheplanet. Muchoftheprocessingoftheimagesweseeactually happensinsideourbrains:theroleoftheeyeistocapture lightinawaythatitcanbecarriedtothebrainfor processingasanimage.Oureyes,likethoseofevery creaturewithaskullandbackbone,arelikelittlecameras. Afterlightfromtheoutsideenterstheeye,itisfocusedona screenatthebackoftheeyeball.Lighttravelsthrough severallayersasittraversesthispath.Firstitpasses throughthecornea,athinlayerofcleartissuethatcovers thelens.Theamountoflightthatenterstheeyeis controlledbyadiaphragm,calledtheiris,whichdilatesand contractsbytheactionofinvoluntarymuscles.Thelight thenpassesthroughthelens,which,asacameradoes, focusestheimage.Tinymusclessurroundthelens;asthese musclescontract,theychangethelens’sshape,thus focusingimagesfromnearandfar.Ahealthylensisclear andmadeupofspecialproteinsthatgiveititsdistinctive shapeandlight-gatheringproperties.Theseproteins, knownaslenscrystallins,areexceptionallylong-lived, 199 allowingthelenstocontinuefunctioningasweage.The screenonwhichallofthelightisprojected,theretina,is loadedwithbloodvesselsandlightreceptors.Theselight receptorssendsignalstoourbrainthatwetheninterpret asimages.Theretinaabsorbsthelightviasensitivelightgatheringcells.Therearetwotypesofsuchcells:oneis verysensitivetolight,theotherlessso.Themoresensitive cellsrecordonlyinblackandwhite;thelesssensitivecells recordincolor.Ifwelookaroundtheanimalworld,wecan assesswhetheranimalsarespecializedfordaylightornight bylookingatthepercentagesofeachtypeoflight-sensing cellintheireyes.Inhumansthesecellsmakeupabout70 percentofallthesensorycellsinourbody.Thatisaclear statementabouthowimportantvisionistous. Ourcamera-likeeyeiscommontoeverycreaturewitha skull,fromfishtomammals.Inothergroupsofanimalswe finddifferenteyes,rangingfromsimplepatchesofcells specializedtodetectlight,toeyeswithcompoundlenses suchasthosefoundinflies,toprimordialversionsofour owneye.Thekeytounderstandingthehistoryofoureyes istounderstandtherelationshipbetweenthestructures thatmakeourcamera-eyeandthosethatmakealltheother kindsofeyes.Todothis,wewillstudythemoleculesthat gatherlight,thetissuesweusetosee,andthegenesthat makethewholething. 200 Eyescomeintofocus:fromprimitivelight-capturing devicesininvertebratestoourcamera-typeeyewitha lens.Aseyesevolve,visualacuityincreases. LIGHT-GATHERINGMOLECULES Thereallyimportantworkinthelight-gatheringcells happensinsidethemoleculethatactuallycollectslight. 201 Whenthismoleculeabsorbslight,itchangesshapeand breaksupintotwoparts.Onepartisderivedfromvitamin A,theotherfromaproteinknownasanopsin.Whenthe opsinbreaksoff,itinitiatesachainreactionthatleadstoa neuronsendinganimpulsetoourbrain.Weusedifferent opsinstoseeinblackandwhiteandincolor.Justasan inkjetprinterneedsthreeorfourinkstoprintincolor,we needthreelight-gatheringmoleculestoseeincolor.For black-and-whitevision,weuseonlyone. Theselight-gatheringmoleculeschangeshapeinthe light,thenrechargeinthedarkandgobacktotheirnormal state.Theprocesstakesafewminutes.Weallknowthis frompersonalexperience:gofromabrightplaceintoadark roomanditisvirtuallyimpossibletoseefaintobjects.The reasonisthatthelight-gatheringmoleculesneedtimeto recharge.Afterafewminutes,visioninthedarkreturns. Despitethestunningvarietyofphotoreceptororgans, everyanimalusesthesamekindoflight-capturing moleculetodothisjob.Insects,humans,clams,andscallops alluseopsins.Notonlycanwetracethehistoryofeyes throughdifferencesinthestructureoftheiropsins,butwe havegoodevidencethatwecanthankbacteriaforthese moleculesinthefirstplace. Essentially,anopsinisakindofmoleculethatconveys informationfromtheoutsideofacelltotheinside.Topull offthisfeat,itneedstocarryachemicalacrossthe membranethatencirclesacell.Opsinsuseaspecialized kindofconductorthattakesaseriesofbendsandloopsas 202 ittravelsfromtheoutsidetotheinsideofthecell.Butthis twistedpaththereceptortakesthroughthecellmembrane isnotrandom—ithasacharacteristicsignature.Where elseisthistwistedpathseen?Itisidenticaltopartsof certainmoleculesinbacteria.Theveryprecisemolecular similaritiesinthismoleculesuggestaveryancient propertyofallanimalsextendingallthewaytoourshared historywithbacteria.Inasense,modifiedbitsofancient bacterialieinsideourretinas,helpingustosee. Wecaneventracesomemajoreventsinthehistoryof oureyesbyexaminingopsinsindifferentanimals.Takeone ofthemajoreventsinourprimatepast,thedevelopmentof richcolorvision.Recallthathumansandourclosestape relatives,theOldWorldmonkeys,haveaverydetailedkind ofcolorvisionthatreliesonthreedifferentkindsoflight receptors.Eachofthesereceptorsistunedtoadifferent kindoflight.Mostothermammalshaveonlytwokindsof receptorsandsocannotdiscriminateasmanycolorsaswe can.Itturnsoutthatwecantracetheoriginofourcolor visionbylookingatthegenesthatmakethereceptors.The twokindsofreceptorsmostmammalshavearemadeby twokindsofgenes.Ofourthreereceptor-makinggenes, twoareremarkablylikeoneofthoseinothermammals. Thisseemstoimplythatourcolorvisionbeganwhenone ofthegenesinothermammalsduplicatedandthecopies specializedovertimefordifferentlightsources.Asyou’ll remember,asimilarthinghappenedwithodorreceptor genes. 203 Thisshiftmayberelatedtochangesinthefloraofthe earthmillionsofyearsago.Ithelpstothinkwhatcolor visionwaslikelygoodforwhenitfirstappeared.Monkeys thatliveintreeswouldbenefitbecausecolorvisionenabled themtodiscriminatebetteramongmanykindsoffruitsand leavesandselectthemostnutritiousamongthem.From studyingtheotherprimatesthathavecolorvision,wecan estimatethatourkindofcolorvisionaroseabout55 millionyearsago.Atthistimewefindfossilevidenceof changesinthecompositionofancientforests.Beforethis time,theforestswererichinfigsandpalms,whicharetasty butallofthesamegeneralcolor.Laterforestshadmoreofa diversityofplants,likelywithdifferentcolors.Itseemsa goodbetthattheswitchtocolorvisioncorrelateswitha switchfromamonochromaticforesttoonewitharicher paletteofcolorsinfood. TISSUES Animaleyescomeintwoflavors;oneisseenin invertebrates,theotherinvertebrates,suchasfishand humans.Thecentralideaisthattherearetwodifferent waysofincreasingthelight-gatheringsurfaceareaineye tissue.Invertebrates,suchasfliesandworms,accomplish thisbyhavingnumerousfoldsinthetissue,whileour lineageexpandsthesurfaceareabyhavinglotsoflittle projectionsextendingfromthetissueliketinybristles.A 204 hostofotherdifferencesalsorelatetothesedifferentkinds ofdesigns.Lackingfossilsattherelevantphaseofhistory,it wouldseemthatwewouldneverbeabletobridgethe differencesbetweenoureyesandthoseofinvertebrates. Thatis,until2001,whenDetlevArendtthoughttostudythe eyesofaveryprimitivelittleworm. Polychaetesareamongthemostprimitivelivingworms known.Theyhaveaverysimplesegmentedbodyplan,and theyalsohavetwokindsoflight-sensingorgans:aneye and,buriedundertheirskin,apartoftheirnervoussystem thatisspecializedtopickuplight.Arendttooktheseworms apartbothphysicallyandgenetically.Knowledgeofthe genesequenceofouropsingenesandthestructureofour light-gatheringneuronsgaveArendtthetoolstostudyhow polychaetesaremade.Hefoundthattheyhadelementsof bothkindsofanimalphotoreceptors.Thenormal“eye”was madeupofneuronsandopsinsliketheeyeofany invertebrate.Thetinyphotoreceptorsundertheskinwere anothermatteraltogether.Theyhad“vertebrate”opsins andcellularstructureevenwiththelittlebristle-like projections,butinprimitiveform.Arendthadfoundaliving bridge,ananimalwithbothkindsofeyes,oneofwhich— ourkind—existedinaveryprimitiveform.Whenwelook toprimitiveinvertebrates,wefindthatthedifferentkinds ofanimaleyessharecommonparts. GENES 205 Arendt’sdiscoveryleadstoyetanotherquestion.Itisone thingforeyestosharecommonparts,buthowcaneyes thatlooksodifferent—suchasthoseofworms,flies,and mice—becloselyrelated?Fortheanswer,letusconsider thegeneticrecipethatbuildseyes. Attheturnofthetwentiethcentury,MildredHogewas recordingmutationsinfruitflieswhenshefoundaflythat hadnoeyeswhatsoever.Thismutantwasnotanisolated case,andHogediscoveredthatshecouldbreedawholeline ofsuchflies,whichshenamedeyeless.Later,asimilar mutationwasdiscoveredinmice.Someindividualshad smalleyes;otherslackedwholeportionsoftheheadand face,includingtheireyes.Asimilarconditioninhumansis knownasaniridia;affectedindividualsaremissinglarge piecesoftheireyes.Intheseverydifferentcreatures—flies, mice,andhumans—geneticistswerefindingsimilarkinds ofmutants. Abreakthroughcameintheearly1990s,when laboratoriesappliednewmoleculartechniquesto understandhoweyelessmutantsaffectedeyedevelopment. Mappingthegenes,theywereabletolocalizethebitsof DNAresponsibleforthemutations.WhentheDNAwas sequenced,itturnedoutthatthefly,mouse,andhuman genesresponsibleforeyelessnesshadsimilarDNA structuresandsequences.Inaveryrealsense,theyarethe samegene. Whatdidwelearnfromthis?Scientistshadidentifieda singlegenethat,whenmutated,producedcreatureswith 206 smalleyesornoeyesatall.Thismeantthatthenormal versionofthegenewasamajortriggerfortheformationof eyes.Nowcamethechancetodoexperimentstoaska wholeotherkindofquestion.Whathappenswhenwemess withthegene,turningitonandoffinthewrongplaces? Flieswereanidealsubjectforthiswork.Duringthe 1980s,anumberofverypowerfulgenetictoolswere developedthroughworkonflies.Ifyouknewagene,ora DNAsequence,youcouldmakeaflylackingthegeneor,the reverse,aflywiththegeneactiveinthewrongplaces. Usingthesetools,WalterGehringstartedplayingaround withtheeyelessgene.Gehring’steamwasabletomakethe eyelessDNAactiveprettymuchanywheretheywanted:in theantenna,onthelegs,onthewings.Whenhisteamdid this,theyfoundsomethingstunning.Iftheyturnedonthe eyelessgeneintheantenna,aneyegrewthere.Ifthey turnedontheeyelessgeneonabodysegment,aneye developedthere.Everywheretheyturnedonthegene,they wouldgetaneweye.Totopitalloff,someofthemisplaced eyesshowedanascentabilitytorespondtolight.Gehring haduncoveredamajortriggerintheformationofeyes. Gehringdidn’tstopthere;hebeganswappinggenes betweenspecies.Theytookthemouseequivalentofeyeless, Pax6,andturneditoninafly.Themousegeneproduceda neweye.Andnotjustanyeye—aflyeye.Gehring’slabfound theycouldusethemousegenetotriggertheformationofan extraflyeyeanywhere:ontheback,onawing,nearthe mouth.WhatGehringhadfoundwasamasterswitchfor 207 eyedevelopmentthatwasvirtuallythesameinamouse andafly.Thisgene,Pax6,initiatedacomplexchain reactionofgeneactivitythatultimatelyledtoanewflyeye. Wenowknowthateyeless,orPax6,controls developmentineverythingthathaseyes.Theeyesmay lookdifferent—somewithalens,somewithout;some compound,somesimple—butthegeneticswitchesthat makethemarethesame. Whenyoulookintoeyes,forgetaboutromance,creation, andthewindowsintothesoul.Withtheirmolecules,genes, andtissuesderivedfrommicrobes,jellyfish,worms,and flies,youseeanentiremenagerie. 208