第一章分子遺傳學(xué)基礎(chǔ)2010

Chapter1MolecularGenetics

第一章分子遺傳學(xué)基礎(chǔ)Nucleicacidsaregeneticmaterials核酸是遺傳物質(zhì)Structureofnucleicacids核酸的結(jié)構(gòu)Genestructure基因結(jié)構(gòu)Synthesisofnucleicacids核酸的合成Translation:synthesisofprotein蛋白質(zhì)的合成--翻譯Nucleicacidsaregeneticmaterials核酸是遺傳物質(zhì)Chromosome染色體protein蛋白質(zhì)DNARNAWhichoneisgeneticmaterial?哪一個是遺傳物質(zhì)？ExperimentsprovethatDNAisthemoleculeofheredity

實驗證明DNA是遺傳物質(zhì)Transformationexperimentwithpneumonia肺炎球菌轉(zhuǎn)化試驗Transfectionexperimentwithbacteriophage噬菌體轉(zhuǎn)染試驗Experimentwithtabauomosaicvirus(TMV)煙草花葉病毒試驗Transformationexperiment肺炎球菌的轉(zhuǎn)化實驗

無毒的RII肺炎球菌（小的）由被殺死的SIII（大的）的DNA轉(zhuǎn)化成有毒的肺炎球菌Streptococuspneumoniae

肺炎球菌S型：多糖組成莢膜，分SI,SII,SIIIR型：無莢膜，分RI,RII,RIIITransformationexperimentwithpneumonia

肺炎球菌感染小鼠實驗

象加熱殺死的SIII能使不致病的RII變成能致病的SIII，這種現(xiàn)象叫轉(zhuǎn)化（transformation）

把SIII死菌中能轉(zhuǎn)化RII的物質(zhì)叫轉(zhuǎn)化因子證明轉(zhuǎn)化因子是DNA的實驗AdiagramoftheexperimentthatdemonstratedthatDNAistheactivematerialinbacterialtransformation

證明DNA是細(xì)菌轉(zhuǎn)化活性物質(zhì)試驗圖示TransfectionexperimentwithbacteriophageT2

T2噬菌體的侵染實驗(I)T2噬菌體的侵染實驗(II)Experimentwithtabauomosaicvirus(TMV)煙草花葉病毒感染試驗Keypoints:Thegeneticinformationoflivingorganisms

isstoredindeoxyriboncleicacid(DNA).Insome

viruses,ribonucleicacid(RNA)isthegeneticmaterial

要點：生物的遺傳信息儲存在DNA上。在某些病毒中，RNA

是遺傳物質(zhì)。

通過什么實驗證實DNA是遺傳物質(zhì)？還有別的證據(jù)說明這一結(jié)論嗎？Nucleicacids核酸脫氧核糖核酸(DNA)核糖核酸(RNA)Structureofnucleicacids

核酸的結(jié)構(gòu)雙螺旋的發(fā)現(xiàn)—一場激烈的競賽鮑林研究小組的工作：三螺旋DNA分子模型威爾金斯、富蘭克林研究小組的工作：X射線衍射圖沃生、克里克研究組的工作

Sizeofgenome基因組大小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的基本組成單位是脫氧核苷酸。每個脫氧核苷酸含有一個堿基，一個脫氧核糖和一個磷酸基。堿基結(jié)構(gòu)式Chargaff法則腺嘌呤與胸腺嘧啶的克分子數(shù)相等“A”=“T”鳥嘌呤與胞嘧啶的克分子數(shù)相等“G”=“C”Watson和Crick在<自然>上發(fā)表的論文TheWatson-Crickdouble-helix

DNA雙螺旋結(jié)構(gòu)模型要點DNAusuallyexistsasdoublehelix,withthetwostrandsheldtogetherbyhydrogenbondsbetweenthecomplementarybases:ApairedwithTandGpairedwithC.

DNA分子是由兩條同軸反向互相纏繞的多核甘酸鏈組成的雙螺旋結(jié)構(gòu)糖和磷酸排在外面構(gòu)成骨架,兩鏈相應(yīng)的核甘酸的堿基互相配對由氫鍵連接排列在內(nèi)側(cè)ThebasepairsinDNAarestackedabout0.34nmapart,with10basepairsperturn(360゜)ofthedoublehelix雙螺旋直徑為20A，螺距為34A,包含10對堿基糖-磷酸基團(tuán)骨架（黑色）以及堿基（彩色）DNA雙螺旋橫斷面

RNA的基本結(jié)構(gòu)單位是核苷酸，它由含氮堿基（A、G、C、U），核糖和磷酸基構(gòu)成。StructureofRNA含氮堿基（A、G、C、U）和核酸RNA的分類mRNA:冒子結(jié)構(gòu)和尾巴tRNA：三葉草結(jié)構(gòu)rRNA：大亞基和小亞基microRNADNA和RNA結(jié)構(gòu)上有何異同？KeypointsNucleicacidsareoftwotypes:DNAandRNA核酸有兩種類型:DNA和RNADNAusuallyexistsasdoublehelix,withthetwostrandsheldtogetherbyhydrogenbondsbetweenthecomplementarybases:ApairedwithTandGpairedwithCDNA通常以雙螺旋的形式存在,兩股鏈通過互補堿基間的氫鍵結(jié)合在一起:A與T和G與C配對ThecomplementarityofthetwostrandsofadoublehelixmakesDNAuniquelysuitedtostoreandtransmitgeneticinformationfromgenerationtogeneration雙螺旋中兩股鏈的互補使DNA特別適合存儲與在世代間傳遞遺傳信息Thetwostrandsofadoublehelixhaveoppositechemicalpolarity雙螺旋中兩股鏈有著相反的化學(xué)極性RNAusuallyexistsasasingle-strandedmoleculeRNA通常以單股分子的形式存在TestingyourknowledgeTheE.colivirusΦX174storesitsgeneticinformationinsingle-strandedDNA.WhenDNAwasextractedfromΦX174virusparticlesandanalyzed,21percentofthebaseswerefoundtobeGresidues.Fromthisinformation,canyoudeterminewhatpercentageofthebasesinthisDNAwerethymineresidues?Ifso,whatpercentage?Ifnot,whynot?

Genestructure基因結(jié)構(gòu)Evolutionoftheconceptofthegene:summary基因概念的發(fā)展：概述Evolutionoftheconceptofthegene:function基因概念的發(fā)展：功能Evolutionoftheconceptofthegene:structure基因概念的發(fā)展：結(jié)構(gòu)Ageneticdefinitionofthegene：基因的遺傳含義Complexgene-proteinrelationships復(fù)雜的基因-蛋白質(zhì)關(guān)系Evolutionoftheconceptofthegene:summaryGenestructure基因結(jié)構(gòu)(a)Typicalprokaryoticgene典型的原核生物基因(b)Typicaleukaryoticgene典型的真核生物基因Genestructure基因結(jié)構(gòu)

TheconceptofthegenehasundergonemanyrefinementssinceitsdiscoverybyMendelin1866.Mostgenesencodeonepolypeptideandcanbeoperationallydefinedbythecomplementationtest

從1866年孟德爾定律發(fā)現(xiàn)以來基因的概念經(jīng)歷了許多變化，大部分基因編碼一條多肽，可以通過互補測驗來定義。Evolutionoftheconceptofthegene:functionMendel:constantfactorscontrollingphenotypictraits孟德爾：控制表型性狀的永久因子Garrod:onemutantgene-onemetabolicblock加諾德：一個突變基因-一種代謝障礙Earlyevidencethatenzymesarecontrolledbygenes基因控制酶BeadleandTatum:Onegene-oneenzyme：一個基因-一種酶Onegene-onepolypeptide一個基因-一條多肽Mendel:constantfactorscontrollingphenotypictraits控制表型性狀的永久因子Garrod:onemutantgene-onemetabolicblock一個突變基因-一種代謝障礙Earlyevidencethatenzymesarecontrolledbygenes基因控制酶BeadleandTatum:Onegene-oneenzyme一個基因-一種酶Onegene-onepolypeptide一個基因-一條多肽

Theexistenceofabasicgeneticelement,thatcontrolledaspecificphenotypictraitwasestablishedbyMendel’sworkin1866.SincethediscoveryofMendel’sresultsin1900,theconceptofthegenehasevolvedfromunitthatcanmutatetocauseaspecificblockinmeta-bolism,totheunitspecifyingoneenzyme,tothesequenceofnucleotidepairsinDNAencodingonepolypeptidechain.Evolutionoftheconceptofthegene:structure基因概念的發(fā)展：結(jié)構(gòu)Thepre-1940Beads-on-a-stringconcept1940前的概念Discoveryofrecombinationwithinthegene基因內(nèi)部重組的發(fā)現(xiàn)Recombinationbetweenadjacentnucleotidepairs相鄰核苷酸的重組Colinearitybetweenthecodingsequenceofageneanditspolypeptideproduct一個基因編碼序列與其多肽產(chǎn)物的同線性關(guān)系

Theconceptofthegenehasevolvedfromabeadonastring,notdivisiblebyrecombinationormutation,toasequenceofnucleotidepairsinDNAencodingonepolypeptidechain.Theunitofgeneticmaterialnotdivisiblebyrecombinationormutationisthesinglenucleotidepair.基因的概念從不能被重組或突變分開的一條串珠中的一顆變?yōu)镈NA上編碼一條多肽的核苷酸序列.重組或突變不可分的遺傳單位是單個核苷酸.Ageneticdefinitionofthegene

基因的遺傳含義Thecomplementationtestasanoperationaldefinitionofthegene基因動態(tài)定義的互補測驗Intrageniccomplementation基因內(nèi)互補測驗Limitationsontheuseofthecomplementationtest運用互補測驗的局限性Thecomplementationtestasanoperationaldefinitionofthegene互補測驗定義基因Thearrangementofgeneticmarkersincisandtranshetero-zygotes順式與反式雜合子中遺傳標(biāo)記的排列Thecomplementationtestasanoperationaldefinitionofthegene互補測驗定義基因Thecis-transpositioneffect順反位置效應(yīng)Thecomplementationtestasanoperationaldefinitionofthegene互補測驗定義基因Thecistest順式測驗Thecomplementationtestasanoperationaldefinitionofthegene互補測驗定義基因Thetranstest反式測驗Intrageniccomplementation基因內(nèi)互補測驗Intrageniccomplementationmayoccurwhenaproteinisamultimercontainingatleasttwocopiesofonegeneproduct在蛋白質(zhì)屬于一個基因至少含有兩個拷貝時基因內(nèi)的互補也會出現(xiàn)Limitationsontheuseofthecomplementationtest互補測驗的局限性

Thecomplementationortranstestprovidesanoperationaldefinitionofthegene;itisusedtodeterminewhethermutationsareinthesamegeneordifferentgenes.Intrageniccomplementationmayoccurwhenaproteinisamultimercontainingatleasttwocopiesofonegeneproduct.Complexgene-proteinrelationships

復(fù)雜的基因-蛋白質(zhì)關(guān)系A(chǔ)lternatepathwaysoftranscriptsplicing:proteinisoforms

轉(zhuǎn)錄物剪接的不同方式：蛋白質(zhì)同系物Assemblyofgenesduringdevelopment:humanantibody發(fā)育過程中基因的組裝：人的抗體Alternatepathwaysoftranscriptsplicing:proteinisoforms

轉(zhuǎn)錄剪接的不同通路真核基因的一般結(jié)構(gòu)TestingyourknowledgeTheredalgaPolyides

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