Gene-X-ppt(Gene10-基因十)--Chapter04

Chapter4TheInterruptedGene4.1Introduction•interruptedgene–Ageneinwhichthecodingsequenceisnotcontinuousduetothepresenceofintrons.•primary(RNA)transcript–TheoriginalunmodifiedRNAproductcorrespondingtoatranscriptionunit.•RNAsplicing–TheprocessofexcisingintronsfromRNAandconnectingtheexonsintoacontinuousmRNA.4.1Introduction•intron–AsegmentofDNAthatistranscribed,butlaterremovedfromwithinthetranscriptbysplicingtogetherthesequences(exons)oneithersideofit.•maturetranscript–AmodifiedRNAtranscript.Modificationmayincludetheremovalofintronsequencesandalterationstothe5′and3′ends.FIGURE01:InterruptedgenesareexpressedviaaprecursorRNA4.2AnInterruptedGeneConsistsofExonsandIntrons•IntronsareremovedbyRNAsplicing,whichoccursincisinindividualRNAmolecules.•Mutationsinexonscanaffectpolypeptidesequence;mutationsinintronscanaffectRNAprocessingandhencemayinfluencethesequenceand/orproductionofapolypeptide.FIGURE02:ExonsremaininthesameorderinmRNAasinDNA,butdistancesalongthegenedonotcorrespond4.3ExonandIntronBaseCompositionsDiffer•Thefour“rules”forDNAbasecompositionarethefirstandsecondparityrules,theclusterrule,andtheGCrule.•Thesecondparityrulesuggestsanextrusionofstructuredstem-loopsegmentsfromduplexDNA,whichwouldbegreaterinintrons.•Therulesrelatetogenomiccharacteristics,or“pressures,”thatconstitutethegenomephenotype.4.4OrganizationofInterruptedGenesMayBeConserved•IntronscanbedetectedwhengenesarecomparedwiththeirRNAtranscriptionproductsbyeitherrestrictionmapping,electronmicroscopy,orsequencing.•cDNA–Asingle-strandedDNAcomplementarytoanRNA,synthesizedfromitbyreversetranscriptioninvitro.FIGURE03:ComparisonoftherestrictionmapsofcDNAandgenomicDNAformouseβ-globin4.4OrganizationofInterruptedGenesMayBeConserved•Thepositionsofintronsareusuallyconservedwhenhomologousgenesarecomparedbetweendifferentorganisms.–Thelengthsofthecorrespondingintronsmayvarygreatly,though.•Intronsusuallydonotencodeproteins.FIGURE05:MammaliangenesforDHFRhavethesamerelativeorganizationofshortexonsandlongintrons,butvaryinthelengthsofintrons4.5ExonSequencesunderNegativeSelectionAreConservedbutIntronsVary•Comparisonsofrelatedgenesindifferentspeciesshowthatthesequencesofthecorrespondingexonsareusuallyconserved,butthesequencesoftheintronsmuchlessso,whentheexonsareunderselectivepressuretoretainthecapacitytoencodeusefulproteins.FIGURE06:RelatedgenesdivergeintheintronsDataprovidedbyPhilipLeder,HarvardMedicalSchool4.6ExonSequencesunderPositiveSelectionVarybutIntronsAreConserved•Underpositiveselectionanindividualwithanadvantageousmutationisabletoproducemoreprogenythanotherswithoutthemutation.•Duetointrinsicgenomicpressures,suchasthatwhichconservesthepotentialtoextrudestem-loopsfromduplexDNA,intronsevolvemoreslowlythanexonsthatareunderpositiveselectionpressure.ModifiedfromD.R.Forsdyke,ConservationofStem-LoopPotentialinIntronsofSnakeVenomPhospholipaseA2Genes:AnApplicationofFORS-DAnalysis,Mol.Biol.Evol.,vol.12(6),pp.1157-1165,bypermissionofOxfordUniversityPress.FIGURE07:Thesequencesofsnakevenomphospholipasegenesdifferincodingregionsbutarecloselyrelatedinintronsandflankingregions4.7GenesShowaWideDistributionofSizes•MostgenesareuninterruptedinS.cerevisiae,butareinterruptedinmulticellulareukaryotes.FIGURE08:Interruptedgenespredominateinhighereukaryotes4.7GenesShowaWideDistributionofSizes•Exonsareusuallyshort,typicallycodingfor100aminoacids.FIGURE10:Exonsaretypically100-200bp4.7GenesShowaWideDistributionofSizes•Intronsareshortinunicellular/oligocellulareukaryotes,butcanbemanykbinmulticellulareukaryotes.•Theoveralllengthofageneisdeterminedlargelybyitsintrons.FIGURE11:Intronshavewidelengthvariation4.8SomeDNASequencesCodeforMoreThanOnePolypeptide•Usageofalternativetranslationinitiationorterminationcodonsallowsonepolypeptidetobeequivalenttoafragmentofanother.•overlappinggene–Ageneinwhichpartofthesequenceisfoundwithinpartofthesequenceofanothergene.FIGURE12:Alternativestarts(orstops)generaterelatedproteins4.8SomeDNASequencesCodeforMoreThanOnePolypeptide•DifferentpolypeptidescanbeproducedfromthesamesequenceofDNAwhenthemRNAisreadindifferentreadingframes(astwooverlappinggenes).FIGURE13:Overlappingtripletsmaybeusedindifferentreadingframes4.8SomeDNASequencesCodeforMoreThanOnePolypeptide•Otherwiseidenticalpolypeptides,differingbythepresenceorabsenceofcertainregions,canbegeneratedbyalternativesplicingwhencertainexonsareincludedorexcluded.–Thismaytaketheformofincludingorexcludingindividualexons,orofchoosingbetweenalternativeexons.FIGURE15:Differentcombinationsofexonsareusedinalternativesplicing4.9SomeExonsCanBeEquatedwithProteinFunctionalDomains•Proteinscanconsistofindependentfunctionalmodulestheboundariesofwhich,insomecases,canbeequatedwiththoseofexons.FIGURE16:Immunoglobulinlightchainsandheavychainsarecodedbygeneswhoseexpressedstructurescorrespondwiththedistinctdomainsintheprotein4.9SomeExonsCanBeEquatedwithProteinFunctionalDomains•Theexonsofsomegenesappearhomologoustotheexonsofothers,suggestingacommonexonancestry.FIGURE17:Exonsintwoproteinscanberelated4.10MembersofaGeneFamilyHaveaCommonOrganizatio