遗传和遗传物质.ppt

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1、第六章遗传和遗传物质授课教师：牛登科 010-5880206010-58802064 4Charles DarwinnWhenCharlesDarwinproposedhistheoryofevolutionin1859,oneofitsmajorproblemswasthelackofanunderlyingmechanismforheredity.nDarwinbelievedinamixofblendinginheritanceandtheinheritanceofacquiredtraits(pangenesis).Blendinginheritancewouldleadtounifo

2、rmityacrosspopulationsinonlyafewgenerationsandthuswouldremovevariationfromapopulationonwhichnaturalselectioncouldact.ThisledtoDarwinadoptingsomeLamarckianideasinlatereditionsofOn the Origin of Species andhislaterbiologicalworks.nTheinheritanceofacquiredtraitswasshowntohavelittlebasisinthe1880swhenAu

3、gustWeismanncutthetailsoffmanygenerationsofmiceandfoundthattheiroffspringcontinuedtodeveloptails.GregorMendelwasinspiredbybothhisprofessorsattheUniversityofOlomouc(i.e.FriedrichFranz&JohannKarlNestler)andhiscolleaguesatthemonastery(e.g.,FranzDiebl)tostudyvariationinplants,andheconductedhisstudyinthe

4、monasterys2hectareexperimentalgarden.Between1856and1863Mendelcultivatedandtestedsome29,000peaplants(i.e.,Pisum sativum).Hisexperimentsledhimtomaketwogeneralizations,theLawofSegregationandtheLawofIndependentAssortment,whichlaterbecameknownasMendelsLawsofInheritance.WhenMendelspaperwaspublishedin1866i

5、nVerhandlungen des naturforschenden Vereins Brnn,itwasseenasessentiallyabouthybridizationratherthaninheritanceandhadlittleimpactandwascitedaboutthreetimesoverthenextthirty-fiveyears.Gregor MendelFather of geneticsnAftercompletinghisworkwithpeas,Mendelturnedtoexperimentingwithhoneybeestoextendhiswork

6、toanimals.Heproducedahybridstrain,butfailedtogenerateaclearpictureoftheirhereditybecauseofthedifficultiesincontrollingmatingbehaviorsofqueenbees.Healsodescribednovelplantspecies,andthesearedenotedwiththebotanicalauthorabbreviationMendel.nAfterhewaselevatedasabbotin1868,hisscientificworklargelyended,

7、asMendelbecameconsumedwithhisincreasedadministrativeresponsibilities,especiallyadisputewiththecivilgovernmentovertheirattempttoimposespecialtaxesonreligiousinstitutions.nAfterhisdeath,thesucceedingabbotburnedallpapersinMendelscollection,tomarkanendtothedisputesovertaxation.Gregor MendelFather of gen

8、eticsnMendelsworkwasrejectedatfirst,andwasnotwidelyaccepteduntilafterhedied.nBy1900,researchaimedatfindingasuccessfultheoryofdiscontinuousinheritanceratherthanblendinginheritanceledtoindependentduplicationofhisworkbyHugodeVriesandCarlCorrens,andtherediscoveryofMendelswritingsandlaws.ThoughErichvonTs

9、chermakwasoriginallyalsocreditedwithrediscovery,thisisnolongeracceptedbecausehedidnotunderstandMendelslaws.Rediscovery of Mendels worknThesynthesis,producedbetween1936and1947,reflectstheconsensusabouthowevolutionproceeds.Thepreviousdevelopmentofpopulationgenetics,between1918and1932,wasastimulus,asit

10、showedthatMendeliangeneticswasconsistentwithnaturalselectionandgradualevolution.nThemodernsynthesissolveddifficultiesandconfusionscausedbythespecializationandpoorcommunicationbetweenbiologistsintheearlyyearsofthe20thcentury.AtitsheartwasthequestionofwhetherMendeliangeneticscouldbereconciledwithgradu

11、alevolutionbymeansofnaturalselection.Asecondissuewaswhetherthebroad-scalechanges(macroevolution)seenbypalaeontologistscouldbeexplainedbychangesseeninlocalpopulations(microevolution).nThesynthesisincludedevidencefrombiologists,trainedingenetics,whostudiedpopulationsinthefieldandinthelaboratory.Thesyn

12、thesisdrewtogetherideasfromseveralbranchesofbiologywhichhadbecomeseparated,particularlygenetics,cytology,systematics,botany,morphology,ecologyandpaleontology.nJulianHuxleyinventedtheterminhisbook,Evolution:The Modern Synthesis(1942).OthermajorfiguresincludeR.A.Fisher,TheodosiusDobzhansky,J.B.S.Halda

13、ne,SewallWright,E.B.Ford,ErnstMayr,BernhardRensch,SergeiChetverikov,GeorgeGaylordSimpson,andG.LedyardStebbins.Modern evolutionary synthesisn1865:GregorMendelspaper,ExperimentsonPlantHybridizationn1869:FriedrichMiescherdiscoversaweakacidinthenucleiofwhitebloodcellsthattodaywecallDNAn1880-1890:Walther

14、Flemming,EduardStrasburger,andEdouardvanBenedenelucidatechromosomedistributionduringcelldivisionn1903:WalterSuttonandTheodorBoverihypothesizesthatchromosomes,whichsegregateinaMendelianfashion,arehereditaryunitsn1908:Hardy-Weinberglawderived.n1910:ThomasHuntMorganshowsthatgenesresideonchromosomesn191

15、3:AlfredSturtevantmakesthefirstgeneticmapofachromosome:lineararrangedgenesClassical geneticsn1918:RonaldFisherpublishesTheCorrelationBetweenRelativesontheSuppositionofMendelianInheritancethemodernsynthesisofgeneticsandevolutionarybiologystarts.Theoriginofpopulationgenetics.n1928:FrederickGriffithdis

16、coversthathereditarymaterialfromdeadbacteriacanbeincorporatedintolivebacterian1941:EdwardLawrieTatumandGeorgeWellsBeadleshowthatgenescodeforproteins;Classical geneticsn1944:AveryetalshowedDNAasthegeneticmaterialn1948:BarbaraMcClintockdiscoverstransposonsinmaizen1950:ErwinChargaffshowsthattheamountof

17、adenine,A,tendstobeequaltothatofthymine,T;andC=G.n1952:TheHershey-Chaseexperimentprovesthegeneticinformationofphages(andallotherorganisms)tobeDNAn1953:DNAstructureisresolvedtobeadoublehelixbyJamesD.WatsonandFrancisCrickn1958:TheMeselson-StahlexperimentdemonstratesthatDNAissemiconservativelyreplicate

18、dGenetic:the DNA eran1961-1967:Combinedeffortsofscientistscrackthegeneticcode,includingMarshallNirenberg,HarGobindKhorana,SydneyBrenner&FrancisCrickn1964:HowardTeminshowedusingRNAvirusesthatthedirectionofDNAtoRNAtranscriptioncanbereversedn1970:Restrictionenzymeswerediscoveredinstudiesofabacterium,Ha

19、emophilusinfluenzae,enablingscientiststocutandpasteDNAGenetic:the DNA eran1972:WalterFiersandhisteamdeterminedthesequenceofagene:thegeneforbacteriophageMS2coatproteinn1976:WalterFiersandhisteamdeterminethecompletenucleotide-sequenceofbacteriophageMS2-RNAn1977:DNAissequencedforthefirsttimebyFredSange

20、r,WalterGilbert,andAllanMaxamworkingindependently.Sangerslabsequencetheentiregenomeofbacteriophage-X174.n1983:KaryBanksMullisinventsthepolymerasechainreactionenablingtheeasyamplificationofDNAn1989:ThehumangenethatencodestheCFTRproteinwassequencedbyFrancisCollinsandLap-CheeTsui.Defectsinthisgenecause

21、cysticfibrosis.Genetics:The genomics eran1995:ThegenomeofbacteriumHaemophilus influenzaeisthefirstgenomeofafreelivingorganismtobesequencedn1996:Saccharomyces cerevisiae,ayeastspecies,isthefirsteukaryotegenomesequencetobereleasedn1998:Thefirstgenomesequenceforamulticellulareukaryote,Caenorhabditis el

22、egans,isreleasedn2001:FirstdraftsequencesofthehumangenomearereleasedsimultaneouslybytheHumanGenomeProjectandCeleraGenomics.n2003(14April):SuccessfulcompletionofHumanGenomeProjectwith99%ofthegenomesequencedtoa99.99%accuracy.n2012:TheEncyclopediaofDNAElements(ENCODE)projectrevealedthat80%ofhumangenome

23、isactive.Genetics:The genomics eranThepartofthehumanDNAthathaslongbeenbestunderstoodisaround20,000protein-codinggenes.Thesegenes,however,makeupintotalonlyaround1.5%oftheDNA,andareseparatedfromeachotherbylongstretchesofDNAthatdoesnotcodeforproteins.ThisremainingDNAincludestheso-calledregulome,whichco

24、mprisesavarietyofDNAelementsthatinonewayoranothermodulatetheexpressionofprotein-codinggenes.Ithasnotbeenclear,though,howmuchofthetotalDNAiscomprisedwithintheregulome.Untilrecently,themajorityviewhasbeenthatmuchoftheDNAisjunkDNAthatisnevertranscribedandhasnobiologicalfunction.ThecentralgoaloftheENCOD

25、Eprojectistomapouttheregulome,bydeterminingwhichpartsoftheDNAbelongtoitandthemechanismsbywhichthosepartsinfluencegenetranscription.nTheENCODEConsortiumreportedthattheywereabletoassignbiochemicalfunctionstoover80%ofthegenome.MuchofthiswasfoundtobeinvolvedincontrollingtheexpressionlevelsofcodingDNA,wh

26、ichmakesuplessthan1%ofthegenome.细胞核中的细胞核中的DNA都有用吗？都有用吗？n我们细胞核中的DNA都有用吗？上：历史回顾n我们细胞核中的DNA都有用吗？中：人类基因组测序和ENCODE项目n我们细胞核中的DNA都有用吗？下：任重道远nEddy,S.R.(2012)TheC-valueparadox,junkDNAandENCODE.CurrentBiology,22(21),R898.preprintPDFnNiu,D.K.,andJiang,L.(2012)CanENCODEtellushowmuchjunkDNAwecarryinourgenome?.Bi

27、ochemicalandbiophysicalresearchcommunications430:1340-1343.nGraur,D.,Zheng,Y.,Price,N.,Azevedo,R.B.,Zufall,R.A.,andElhaik,E.(2013)Ontheimmortalityoftelevisionsets:functioninthehumangenomeaccordingtotheevolution-freegospelofENCODE.GenomeBiologyandEvolutiondoi:10.1093/gbe/evt028nDoolittle,W.F.(2013)IsjunkDNAbunk?AcritiqueofENCODE.Proc.Natl.Acad.Sci.USAdoi:10.1073/pnas.1221376110细胞核中的细胞核中的DNA都有用吗？都有用吗？