第一章分子遗传学基础2010

Chapter1MolecularGenetics

第一章分子遗传学基础Nucleicacidsaregeneticmaterials核酸是遗传物质Structureofnucleicacids核酸的结构Genestructure基因结构Synthesisofnucleicacids核酸的合成Translation:synthesisofprotein蛋白质的合成--翻译Nucleicacidsaregeneticmaterials核酸是遗传物质Chromosome染色体protein蛋白质DNARNAWhichoneisgeneticmaterial?哪一个是遗传物质？ExperimentsprovethatDNAisthemoleculeofheredity

实验证明DNA是遗传物质Transformationexperimentwithpneumonia肺炎球菌转化试验Transfectionexperimentwithbacteriophage噬菌体转染试验Experimentwithtabauomosaicvirus(TMV)烟草花叶病毒试验Transformationexperiment肺炎球菌的转化实验

无毒的RII肺炎球菌（小的）由被杀死的SIII（大的）的DNA转化成有毒的肺炎球菌Streptococuspneumoniae

肺炎球菌S型：多糖组成荚膜，分SI,SII,SIIIR型：无荚膜，分RI,RII,RIIITransformationexperimentwithpneumonia

肺炎球菌感染小鼠实验

象加热杀死的SIII能使不致病的RII变成能致病的SIII，这种现象叫转化（transformation）

把SIII死菌中能转化RII的物质叫转化因子证明转化因子是DNA的实验AdiagramoftheexperimentthatdemonstratedthatDNAistheactivematerialinbacterialtransformation

证明DNA是细菌转化活性物质试验图示TransfectionexperimentwithbacteriophageT2

T2噬菌体的侵染实验(I)T2噬菌体的侵染实验(II)Experimentwithtabauomosaicvirus(TMV)烟草花叶病毒感染试验Keypoints:Thegeneticinformationoflivingorganisms

isstoredindeoxyriboncleicacid(DNA).Insome

viruses,ribonucleicacid(RNA)isthegeneticmaterial

要点：生物的遗传信息储存在DNA上。在某些病毒中，RNA

是遗传物质。

通过什么实验证实DNA是遗传物质？还有别的证据说明这一结论吗？Nucleicacids核酸脱氧核糖核酸(DNA)核糖核酸(RNA)Structureofnucleicacids

核酸的结构双螺旋的发现—一场激烈的竞赛鲍林研究小组的工作：三螺旋DNA分子模型威尔金斯、富兰克林研究小组的工作：X射线衍射图沃生、克里克研究组的工作

Sizeofgenome基因组大小PhylumSpeciesGenome(bp)AlgaePyrenomassalina6.6×105MycoplasmaM.pneumoniae1.0×106BacteriumE.coli4.2×106YeastS.cerevisiae1.3×107SlimemoldD.discoideum5.4×107NematodeC.elegans8.0×107InsectD.Melanogaster1.4×108BirdG.domesticus1.2×109AmphibianX.laevis3.1×109MammalH.sapiens3.3×109

Nucleicacidsaremacromoleculescomposedofrepeatingsubunitscallednucleotides.Eachnucleotideiscomposedof(1)aphosphategroup,(2)afive-carbonsugar(pentose),and(3)acyclicnitrogen-containingcompoundcalledabase.

DNA的基本组成单位是脱氧核苷酸。每个脱氧核苷酸含有一个碱基，一个脱氧核糖和一个磷酸基。碱基结构式Chargaff法则腺嘌呤与胸腺嘧啶的克分子数相等“A”=“T”鸟嘌呤与胞嘧啶的克分子数相等“G”=“C”Watson和Crick在<自然>上发表的论文TheWatson-Crickdouble-helix

DNA双螺旋结构模型要点DNAusuallyexistsasdoublehelix,withthetwostrandsheldtogetherbyhydrogenbondsbetweenthecomplementarybases:ApairedwithTandGpairedwithC.

DNA分子是由两条同轴反向互相缠绕的多核甘酸链组成的双螺旋结构糖和磷酸排在外面构成骨架,两链相应的核甘酸的碱基互相配对由氢键连接排列在内侧ThebasepairsinDNAarestackedabout0.34nmapart,with10basepairsperturn(360゜)ofthedoublehelix双螺旋直径为20A，螺距为34A,包含10对碱基糖-磷酸基团骨架（黑色）以及碱基（彩色）DNA双螺旋横断面

RNA的基本结构单位是核苷酸，它由含氮碱基（A、G、C、U），核糖和磷酸基构成。StructureofRNA含氮碱基（A、G、C、U）和核酸RNA的分类mRNA:冒子结构和尾巴tRNA：三叶草结构rRNA：大亚基和小亚基microRNADNA和RNA结构上有何异同？KeypointsNucleicacidsareoftwotypes:DNAandRNA核酸有两种类型:DNA和RNADNAusuallyexistsasdoublehelix,withthetwostrandsheldtogetherbyhydrogenbondsbetweenthecomplementarybases:ApairedwithTandGpairedwithCDNA通常以双螺旋的形式存在,两股链通过互补碱基间的氢键结合在一起:A与T和G与C配对ThecomplementarityofthetwostrandsofadoublehelixmakesDNAuniquelysuitedtostoreandtransmitgeneticinformationfromgenerationtogeneration双螺旋中两股链的互补使DNA特别适合存储与在世代间传递遗传信息Thetwostrandsofadoublehelixhaveoppositechemicalpolarity双螺旋中两股链有着相反的化学极性RNAusuallyexistsasasingle-strandedmoleculeRNA通常以单股分子的形式存在TestingyourknowledgeTheE.colivirusΦX174storesitsgeneticinformationinsingle-strandedDNA.WhenDNAwasextractedfromΦX174virusparticlesandanalyzed,21percentofthebaseswerefoundtobeGresidues.Fromthisinformation,canyoudeterminewhatpercentageofthebasesinthisDNAwerethymineresidues?Ifso,whatpercentage?Ifnot,whynot?

Genestructure基因结构Evolutionoftheconceptofthegene:summary基因概念的发展：概述Evolutionoftheconceptofthegene:function基因概念的发展：功能Evolutionoftheconceptofthegene:structure基因概念的发展：结构Ageneticdefinitionofthegene：基因的遗传含义Complexgene-proteinrelationships复杂的基因-蛋白质关系Evolutionoftheconceptofthegene:summaryGenestructure基因结构(a)Typicalprokaryoticgene典型的原核生物基因(b)Typicaleukaryoticgene典型的真核生物基因Genestructure基因结构

TheconceptofthegenehasundergonemanyrefinementssinceitsdiscoverybyMendelin1866.Mostgenesencodeonepolypeptideandcanbeoperationallydefinedbythecomplementationtest

从1866年孟德尔定律发现以来基因的概念经历了许多变化，大部分基因编码一条多肽，可以通过互补测验来定义。Evolutionoftheconceptofthegene:functionMendel:constantfactorscontrollingphenotypictraits孟德尔：控制表型性状的永久因子Garrod:onemutantgene-onemetabolicblock加诺德：一个突变基因-一种代谢障碍Earlyevidencethatenzymesarecontrolledbygenes基因控制酶BeadleandTatum:Onegene-oneenzyme：一个基因-一种酶Onegene-onepolypeptide一个基因-一条多肽Mendel:constantfactorscontrollingphenotypictraits控制表型性状的永久因子Garrod:onemutantgene-onemetabolicblock一个突变基因-一种代谢障碍Earlyevidencethatenzymesarecontrolledbygenes基因控制酶BeadleandTatum:Onegene-oneenzyme一个基因-一种酶Onegene-onepolypeptide一个基因-一条多肽

Theexistenceofabasicgeneticelement,thatcontrolledaspecificphenotypictraitwasestablishedbyMendel’sworkin1866.SincethediscoveryofMendel’sresultsin1900,theconceptofthegenehasevolvedfromunitthatcanmutatetocauseaspecificblockinmeta-bolism,totheunitspecifyingoneenzyme,tothesequenceofnucleotidepairsinDNAencodingonepolypeptidechain.Evolutionoftheconceptofthegene:structure基因概念的发展：结构Thepre-1940Beads-on-a-stringconcept1940前的概念Discoveryofrecombinationwithinthegene基因内部重组的发现Recombinationbetweenadjacentnucleotidepairs相邻核苷酸的重组Colinearitybetweenthecodingsequenceofageneanditspolypeptideproduct一个基因编码序列与其多肽产物的同线性关系

Theconceptofthegenehasevolvedfromabeadonastring,notdivisiblebyrecombinationormutation,toasequenceofnucleotidepairsinDNAencodingonepolypeptidechain.Theunitofgeneticmaterialnotdivisiblebyrecombinationormutationisthesinglenucleotidepair.基因的概念从不能被重组或突变分开的一条串珠中的一颗变为DNA上编码一条多肽的核苷酸序列.重组或突变不可分的遗传单位是单个核苷酸.Ageneticdefinitionofthegene

基因的遗传含义Thecomplementationtestasanoperationaldefinitionofthegene基因动态定义的互补测验Intrageniccomplementation基因内互补测验Limitationsontheuseofthecomplementationtest运用互补测验的局限性Thecomplementationtestasanoperationaldefinitionofthegene互补测验定义基因Thearrangementofgeneticmarkersincisandtranshetero-zygotes顺式与反式杂合子中遗传标记的排列Thecomplementationtestasanoperationaldefinitionofthegene互补测验定义基因Thecis-transpositioneffect顺反位置效应Thecomplementationtestasanoperationaldefinitionofthegene互补测验定义基因Thecistest顺式测验Thecomplementationtestasanoperationaldefinitionofthegene互补测验定义基因Thetranstest反式测验Intrageniccomplementation基因内互补测验Intrageniccomplementationmayoccurwhenaproteinisamultimercontainingatleasttwocopiesofonegeneproduct在蛋白质属于一个基因至少含有两个拷贝时基因内的互补也会出现Limitationsontheuseofthecomplementationtest互补测验的局限性

Thecomplementationortranstestprovidesanoperationaldefinitionofthegene;itisusedtodeterminewhethermutationsareinthesamegeneordifferentgenes.Intrageniccomplementationmayoccurwhenaproteinisamultimercontainingatleasttwocopiesofonegeneproduct.Complexgene-proteinrelationships

复杂的基因-蛋白质关系Alternatepathwaysoftranscriptsplicing:proteinisoforms

转录物剪接的不同方式：蛋白质同系物Assemblyofgenesduringdevelopment:humanantibody发育过程中基因的组装：人的抗体Alternatepathwaysoftranscriptsplicing:proteinisoforms

转录剪接的不同通路真核基因的一般结构TestingyourknowledgeTheredalgaPolyides

rotundusstoresitsgeneticinformationindouble-strandedDNA.WhenDNAwasextractedfromP.rotunduscellsandanalyzed,32percentofthebaseswerefoundtobeguanineresidues.Fromthisinformation,canyoudeterminewhatpercentageofthebasesinthethisDNAwerethymineresidues?Ifso,whatpercentage?Ifnot,whynot?Historyofthegene,1860tojustbeforeENCODEDefinition1860s–1900s:GeneasadiscreteunitofheredityDefinition1910s:GeneasadistinctlocusDefinition1940s:GeneasablueprintforaproteinDefinition1950s:GeneasaphysicalmoleculeDefinition1960s:GeneastranscribedcodeDefinition1970s–1980s:Geneasopenreadingframe(ORF)sequencepatternDefinition1990s