Biology Review1

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    BiologyReview(bysomewikimaterial,EssentialCellBiology,andpersonaladds)

    (Maytheforcebewithus)

    1CentralDogmaofmolecularbiologyandimplications

    DNAcontainsthecompletegeneticinformationthatdefines

    thestructureandfunctionofanorganism.Proteinsare

    formedusingthegeneticcodeoftheDNA.Threedifferent

    processesareresponsiblefortheinheritanceofgenetic

    informationandforitsconversionfromoneformto

    another:1.Replication:adoublestrandednucleicacidisduplicatedtogiveidenticalcopies.Thisprocess

    perpetuatesthegeneticinformation.

    2.Transcription:aDNAsegmentthatconstitutesageneisreadandtranscribedintoasinglestrandedsequence

    ofRNA.TheRNAmovesfromthenucleusintothe

    cytoplasm.

    3.Translation:theRNAsequenceistranslatedintoasequenceofaminoacidsastheproteinisformed.

    Duringtranslation,theribosomereadsthreebases(a

    codon)atatimefromtheRNAandtranslatestheminto

    oneaminoacid

    Ineucarioticcells,thesecondstep(transcription)is

    necessarybecausethegeneticmaterialinthenucleusis

    physicallyseparatedfromthesiteofproteinsynthesisinthe

    cytoplasminthecell.Therefore,itisnotpossibletotranslateDNAdirectlyintoprotein,butanintermediarymustbe

    madetocarrytheinformationfromonecompartmenttoan

    other.

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    Belowasimpledescriptionofprokaryoticandeukaryotic

    cells

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    Prokaryoticcells

    Diagramofatypicalprokaryoticcell:

    Theprokaryotecellissimpler,andthereforesmaller,thana

    eukaryotecell,lackinganucleusandmostoftheother

    organellesofeukaryotes.Therearetwokindsof

    prokaryotes:bacteriaandarchaea;theseshareasimilar

    structure.

    Nuclearmaterialofprokaryoticcellconsistsofasingle

    chromosomethatisindirectcontactwithcytoplasm.Here,theundefinednuclearregioninthecytoplasmiscalled

    nucleoid.

    Aprokaryoticcellhasthreearchitecturalregions:

    Ontheoutside,flagellaandpiliprojectfromthecell's

    surface.Thesearestructures(notpresentinall

    prokaryotes)madeofproteinsthatfacilitatemovementand

    communicationbetweencells;

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    Enclosingthecellisthecellenvelopegenerallyconsisting

    ofacellwallcoveringaplasmamembranethoughsome

    bacteriaalsohaveafurthercoveringlayercalledacapsule.

    Theenvelopegivesrigiditytothecellandseparatesthe

    interiorofthecellfromitsenvironment,servingasa

    protectivefilter.Thoughmostprokaryoteshaveacellwall,

    thereareexceptionssuchasMycoplasma(bacteria)and

    Thermoplasma(archaea).Thecellwallconsistsof

    peptidoglycaninbacteria,andactsasanadditionalbarrier

    againstexteriorforces.Italsopreventsthecellfrom

    expandingandfinallybursting(cytolysis)fromosmotic

    pressureagainstahypotonicenvironment.Someeukaryotecells(plantcellsandfungicells)alsohaveacellwall;

    Insidethecellisthecytoplasmicregionthatcontainsthecell

    genome(DNA)andribosomesandvarioussortsof

    inclusions.Aprokaryoticchromosomeisusuallyacircular

    molecule(anexceptionisthatofthebacteriumBorrelia

    burgdorferi,whichcausesLymedisease).Thoughnot

    forminganucleus,theDNAiscondensedinanucleoid.

    ProkaryotescancarryextrachromosomalDNAelementscalledplasmids,whichareusuallycircular.Plasmidsenable

    additionalfunctions,suchasantibioticresistance.

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    Eukaryotic cells

    Main article:Eukaryote

    Diagramofatypicalanimal(eukaryotic)cell,showingsubcellularcomponents.

    Organelles:

    (1)nucleolus

    (2)nucleus

    (3)ribosome(4)vesicle

    (5)roughendoplasmicreticulum (ER)

    (6)Golgiapparatus

    (7)Cytoskeleton

    (8)smoothendoplasmicreticulum

    (9)mitochondria

    (10)vacuole

    (11)cytoplasm

    (12)lysosome

    (13)centrioleswithincentrosome

    Eukaryoticcellsareabout15timeswiderthanatypical

    prokaryoteandcanbeasmuchas1000timesgreaterin

    volume.Themajordifferencebetweenprokaryotesand

    eukaryotesisthateukaryoticcellscontainmembrane-bound

    compartmentsinwhichspecificmetabolicactivitiestake

    place.Mostimportantamongtheseisacellnucleus,a

    membrane-delineatedcompartmentthathousestheeukaryoticcell'sDNA.Thisnucleusgivestheeukaryoteits

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    name,whichmeans"truenucleus."Otherdifferences

    include:

    4. Theplasmamembraneresemblesthatofprokaryotesinfunction,withminordifferencesinthesetup.Cellwallsmayormaynotbepresent.

    5. TheeukaryoticDNAisorganizedinoneormorelinearmolecules,calledchromosomes,whichareassociated

    withhistoneproteins.AllchromosomalDNAisstored

    inthecellnucleus,separatedfromthecytoplasmbya

    membrane.Someeukaryoticorganellessuchas

    mitochondriaalsocontainsomeDNA.

    6. Manyeukaryoticcellsareciliatedwithprimarycilia.Primaryciliaplayimportantrolesinchemosensation,

    mechanosensation,andthermosensation.Ciliamay

    thusbe"viewedassensorycellularantennaethat

    coordinatealargenumberofcellularsignaling

    pathways,sometimescouplingthesignalingtociliary

    motilityoralternativelytocelldivisionand

    differentiation."[7]

    Eukaryotescanmoveusingmotileciliaorflagella.The

    flagellaaremorecomplexthanthoseofprokaryotes.

    DNAReplication(Sum)

    Beforeacelldivides,itsDNAisreplicated(duplicated.)

    BecausethetwostrandsofaDNAmoleculehave

    complementarybasepairs,thenucleotidesequenceofeach

    strandautomaticallysuppliestheinformationneededto

    produceitspartner.IfthetwostrandsofaDNAmolecule

    areseparated,eachcanbeusedasapatternortemplateto

    produceacomplementarystrand.Eachtemplateandits

    newcomplementtogetherthenformanewDNAdouble

    helix,identicaltotheoriginal.Beforereplicationcan

    occurs,thelengthoftheDNAdoublehelixabouttobe

    copiedmustbeunwound.Inaddition,thetwostrands

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    mustbeseparated,muchlikethetwosidesofazipper,by

    breakingtheweakhydrogenbondsthatlinkthepaired

    bases.OncetheDNAstrandshavebeenunwound,they

    mustbeheldaparttoexposethebasessothatnew

    nucleotidepartnerscanhydrogen-bondtothem.The

    enzymeDNApolymerasethenmovesalongtheexposed

    DNAstrand,joiningnewlyarrivednucleotidesintoanew

    DNAstrandthatiscomplementarytothetemplate.

    Eachcellcontainsafamilyofmorethanthirtyenzymesto

    insuretheaccuratereplicationofDNA.

    ThoughDNApolymerasecanelongateapolynucleotide

    strandbyaddingnewnucleotides,itcannotstartastrand

    fromscratchbecauseitcanonlybondnewnucleotidestoa

    freesugar(3')endofanucleotidechain.DNApolymerase

    requirestheassistanceofaprimer,apreviouslyexisting

    shortstrandofDNA(orRNA)thatiscomplementarytothe

    firstpartoftheDNAsegmentbeingcopied.Thissmall

    strandofnucleotidesanneals(binds)bycomplementary

    basepairingtothebeginningoftheareabeingcopied.With

    theprimerinplace,DNApolymeraseisthenabletocontinue

    addingtherestofthepairsofthesegmentuntilanew

    doublestrandofDNAiscompleted.Primersareformed

    fromfreenucleotidesinthecellbyenzymescalledDNA

    primases.

    Thatnucleotidescanbeaddedonlytothesugaror3'endofthegrowingcomplementarychainpresentsnoproblemfor

    thesideoftheDNAchainopeningatitsphosphateor5'

    end.Theprimerthatbindstothefirstfewexposedbases

    willendwithasugar(3')wherethephosphateofanew

    nucleotidecanbeattached.Fromthereon,DNApolymerase

    cancontinuouslysynthesizethegrowingcomplementary

    strand.ThisstrandofDNAiscalledtheleadingstrand.

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    AdifferentchallengefacesDNApolymerasewhenthe

    complementarysideoftheDNAmoleculebeginsunzipping

    fromitssugar(3')towarditsphosphate(5')end.Aprimer

    ofcomplementarymoleculesattachingtotheopeningendof

    thischainwouldhaveaphosphatenotasugaratitsexposed

    endsothatnewnucleotidescouldnotbejoined.Toget

    aroundthisproblem,thisstrandissynthesizedinsmall

    piecesbackwardfromtheoveralldirectionof

    replication.Thisstrandiscalledthelaggingstrand.The

    shortsegmentsofnewlyassembledDNAfromwhichthe

    laggingstrandisbuiltarecalledOkazakifragments.As

    replicationproceedsandnucleotidesareaddedtothe3'endoftheOkazakifragments,theycometomeeteachother.The

    primerfragmentsarethenbootedoutbyenzymesand

    replacedbyappropriateDNAnucleotides.Thewholething

    isthenstitchedtogetherbyanotherenzymecalledDNA

    ligase.

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    BecausehumanDNAissoverylong(withupto80million

    basepairsinachromosome)itunzipsatmultipleplaces

    alongitslengthsothatthereplicationprocessisgoingon

    simultaneouslyathundredsofplacesalongthelengthofthe

    chain.Eventuallytheseareasruntogethertoforma

    completechain.Inhumans,DNAiscopiedatabout50base

    pairspersecond.Theprocesswouldtakeamonth(rather

    thanthehouritactuallydoes)withoutthesemultipleplaces

    onthechromosomewherereplicationcanbegin.DNA

    polymerasemakesveryfewerrors,andmostofthosethat

    aremadearequicklycorrectedbyDNApolymeraseand

    otherenzymesthat"proofread"thenucleotidesaddedintothenewDNAstrand.Ifanewlyaddednucleotideisnot

    complementarytotheoneonthetemplatestrand,these

    enzymesremovethenucleotideandreplaceitwiththe

    correctone.Withthissystem,acell'sDNAiscopiedwith

    lessthanonemistakeinabillionnucleotides.Thisisequal

    toapersoncopying100large(1000page)dictionariesword

    forword,andsymbolforsymbol,withonlyoneerrorforthe

    wholeprocess!

    DNAReplicationineukaryotes:

    DNAreplicationineukaryotesismuchmorecomplicated

    thaninprokaryotes,althoughtherearemanysimilar

    aspects.EukaryoticcellscanonlyinitiateDNAreplicationat

    aspecificpointinthecellcycle,thebeginningofSphase.

    (themaindifferenceisaboutthepreparingphaseinthecell

    cycle,theG1phase,andsomespecializedproteinsmore

    thanintheprokaryaworld)

    Theeukaryoticchromosomesarecontainedwithinanucleusthatisboundedbyadouble-membrane

    nuclearenvelope.

    Herethenucleolusandthenuclearfibrousskeletoncantriggerandlocalizethegeneticactivities

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    MedicalapplicationsofDNAReplication

    ***Registrationswerenotclearatall,soItriedtodigthe

    webtofindthemainmedicalapplicationsofDNA

    Replication,butIcanonlymakealist:

    Forensicstudies Paternitytest Geneticalstudies(tolocalizethepartofthestrandthatruleanentiredisease)

    Historyandanthropology(UsingDNAmeasurementtechniquestobetterunderstandourpasts)

    Nanotechnology(usingDNAitselftodevelopinterestingnewphysicalconceptsinthenano-world)

    GeneticEngineering(Usinganunderstandingofgenestomanipulatephysicalcharactertraits)

    Transcriptionessentials

    TranscriptionistheprocessbywhichaDNAtemplateiscopiedbyRNApolymerasetoproducea

    complementarymoleculeofRNA

    Itinvolvesfourstages:1.BindingofRNApolymerasetopromotersequencesin

    theDNAtemplatestrand

    2.InitiationofRNAsynthesis3.

    ElongationofRNAchain4.Termination

    Intheeukaryoticcellsismorecomplex,onemajordifferenceisthateukaryoticcellshavemultipleforms

    ofRNApolymerasethatarespecializedfor

    synthesizingdifferenttypesofRNA

    ThethreenuclearRNApolymerasesrecognizedifferentfamiliesofDNApromoterseq.Theseeukaryoticpromotersareusuallyboundbytranscriptionfactors

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    thatassociatewithRNA

    polymeraseratherthanby

    RNApolymeraseitself.

    Idontwanttolosetimeontranscription,just

    typetranscriptionanimationonyoutubetoget

    aquicklookatthisprocess

    Checkonthissiteforfurtherinfos:

    http://users.rcn.com/jkimball.ma.ultranet/Bio

    logyPages/T/Transcription.html

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    MedicalApplicationsofTranscriptions

    Proteinsynthesisiscriticaltothegrowthofcells;medicines

    thatworkbykillingcellsoftentargetthisprocess.Amajority

    ofantibioticsworkbydisruptingthetranslationprocess.

    TetracyclineisanantibioticthatinhibitsthebindingoftRNA

    totheassemblysite.Streptomycinworksbycausingthe

    translationprocesstomakemoremistakesthanusualas

    highasonemistakeforevery100aminoacids.Proteinswith

    thismanyerrorsarenotcapableofperformingtheirtasks,

    andthecells(inthiscase,bacteria)die.Streptomycinalso

    inhibitstheinitiationofthesynthesisprocess.***Icouldntfindmore

    TranslationProteinBiosynthesisEssentials

    Duringtranslation,asmallribosomalsubunitattachestoa

    mRNAmolecule.Atthesametime,aninitiatortRNA

    moleculerecognizesandbindstoaspecificcodonsequence

    onthesamemRNAmolecule.Alargeribosomalsubunitthen

    joinsthenewlyformedcomplex.TheinitiatortRNAresides

    inonebindingsiteoftheribosomecalledthePsite,leaving

    thesecondbindingsite,theAsite,open.WhenanewtRNA

    moleculerecognizesthenextcodonsequenceonthemRNA,

    itattachestotheopenAbindingsite.Apeptidebondforms

    connectingtheaminoacidattachedtothetRNAinthePsite

    totheaminoacidattachedtothetRNAintheAbindingsite.

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    AstheribosomemovesalongthemRNAmolecule,thetRNA

    inthePsiteisreleasedandthetRNAintheAsiteis

    translocatedtothePsite.TheAbindingsitebecomesvacant

    againuntilanothertRNAthatrecognizesthenewmRNA

    codontakestheopenposition.Thispatterncontinuesas

    moleculesoftRNAarereleasedfromthecomplex,newtRNA

    moleculesattach,andtheaminoacidchaingrows.The

    ribosomewilltranslatethemRNAmoleculeuntilitreachesa

    terminationcodononthemRNA.

    ***Watchavideo,itisaneasyprocess

    HeresomemoreKey-featuresofthemechanism:

    Translationinvolvesinitiation,elongationandterminationstages

    Duringtheinitiationstage,initiationfactorstriggertheassemblyofmRNA,ribosomalsubunits,initiator

    aminoacyltRNAintoninitiationcomplex

    ChainelongationinvolvessequentialcyclesofaminoacyltRNAbinding,peptidebondformationandtranslocation,witheachcycledrivenbytheactionof

    elongationfactors.Thenetresultisthataminoacyl

    tRNAsaddtheiraminoacidstothegrowing

    polypeptidechaininanorderspecifiedbythecodon

    sequenceinmRNA

    ChainterminationoccurswhenastopcodoninmRNAisrecognizedbyreleasefactors,whichcausesthe

    mRNAandnewlyformedpolypeptidetobereleased

    fromtheribosome

    GTPbindingandhydrolysisarerequiredfortheactionofseveralinitiation,elongationandreleasefactors

    Properfoldingofnewlyproducedpolypeptidechainsisassistedbymolecularchaperones.Abnormalitiesin

    proteinfoldingcanleadtovarioushealthproblems,

    includingAlzheimersdiseaseandmadcowdisease

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    VirusGeneralities

    Avirusisasmallinfectiousagentthatcanreplicateonly

    insidethelivingcellsoforganisms.Mostvirusesaretoo

    smalltobeseendirectlywithalightmicroscope.Viruses

    infectalltypesoforganisms,fromanimalsandplantsto

    bacteriaandarchaea.Sincetheinitialdiscoveryofthe

    tobaccomosaicvirusbyMartinusBeijerinckin1898,about

    5,000viruseshavebeendescribedindetail,althoughthere

    aremillionsofdifferenttypes.Virusesarefoundinalmost

    everyecosystemonEarthandarethemostabundanttypeof

    biologicalentity.Thestudyofvirusesisknownasvirology,asub-specialityofmicrobiology.

    Virusparticles(knownasvirions)consistoftwoorthree

    parts:thegeneticmaterialmadefromeitherDNAorRNA,

    longmoleculesthatcarrygeneticinformation;aproteincoat

    thatprotectsthesegenes;andinsomecasesanenvelopeof

    lipidsthatsurroundstheproteincoatwhentheyareoutside

    acell.Theshapesofvirusesrangefromsimplehelicaland

    icosahedralformstomorecomplexstructures.Theaveragevirusisaboutoneone-hundredththesizeoftheaverage

    bacterium.

    Theoriginsofvirusesintheevolutionaryhistoryoflifeare

    unclear:somemayhaveevolvedfromplasmidspiecesof

    DNAthatcanmovebetweencellswhileothersmayhave

    evolvedfrombacteria.Inevolution,virusesareanimportant

    meansofhorizontalgenetransfer,whichincreasesgenetic

    diversity.Virusesspreadinmanyways;virusesinplantsareoften

    transmittedfromplanttoplantbyinsectsthatfeedonthe

    sapofplants,suchasaphids;virusesinanimalscanbe

    carriedbyblood-suckinginsects.Thesedisease-bearing

    organismsareknownasvectors.Influenzavirusesare

    spreadbycoughingandsneezing.Norovirusandrotavirus,

    commoncausesofviralgastroenteritis,aretransmittedby

    thefaecal-oralrouteandarepassedfrompersontopersonbycontact,enteringthebodyinfoodorwater.HIVisoneof

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    severalvirusestransmittedthroughsexualcontactandby

    exposuretoinfectedblood.Therangeofhostcellsthata

    viruscaninfectiscalledits"hostrange".Thiscanbenarrow

    or,aswhenavirusiscapableofinfectingmanyspecies,

    broad.

    Viralinfectionsinanimalsprovokeanimmuneresponse

    thatusuallyeliminatestheinfectingvirus.Immune

    responsescanalsobeproducedbyvaccines,whichconferan

    artificiallyacquiredimmunitytothespecificviralinfection.

    However,somevirusesincludingthosecausingAIDSand

    viralhepatitisevadetheseimmuneresponsesandresultin

    chronicinfections.Antibioticshavenoeffectonviruses,butseveralantiviraldrugshavebeendeveloped.

    Keyfeatures:

    Structure:

    Avirusparticle,alsoknownasavirion,isessentiallya

    nucleicacid(DNAorRNA)enclosedinaproteinshellorcoat.Virusesareextremelysmall,approximately15-25

    nanometersindiameter.

    GeneticMaterial:

    Virusesmayhavedouble-strandedDNA,double-stranded

    RNA,single-strandedDNAorsingle-strandedRNA.Thetype

    ofgeneticmaterialfoundinaparticularvirusdependsonthenatureandfunctionofthespecificvirus.Thegenetic

    materialisnottypicallyexposedbutcoveredbyaprotein

    coat.

    Theviralgenomecanconsistofaverysmallnumberof

    genesoruptohundredsofgenesdependingonthetypeof

    virus.Notethatthegenomeistypicallyorganizedasalong

    moleculethatisusuallystraightorcircular.

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    Capsids

    Theproteincoatthatenvelopesviralgeneticmaterialis

    knownasacapsid.Acapsidiscomposedofproteinsubunits

    calledcapsomeres.Capsidscanhaveseveralshapes:

    polyhedral,rodorcomplex.Capsidsfunctiontoprotectthe

    viralgeneticmaterialfromdamage.

    Inadditiontotheproteincoat,someviruseshave

    specializedstructures.Forexample,thefluvirushasa

    membrane-likeenvelopearounditscapsid.Theenvelope

    hasbothhostcellandviralcomponentsandassiststhevirusininfectingitshost.Capsidadditionsarealsofoundin

    bacteriophages.Forexample,bacteriophagescanhavea

    protein"tail"attachedtothecapsidthatisusedtoinfect

    hostbacteria.

    VirusReplication

    Virusesareintracellularobligateparasiteswhichmeansthattheycannotreplicateorexpresstheirgeneswithoutthehelp

    ofalivingcell.Asinglevirusparticle(virion)isinandof

    itselfessentiallyinert.Itlacksneededcomponentsthatcells

    havetoreproduce.Whenavirusinfectsacell,itmarshals

    thecell'sribosomes,enzymesandmuchofthecellular

    machinerytoreplicate.Unlikewhatwehaveseenincellular

    replicationprocessessuchasmitosisandmeiosis,viral

    replicationproducesmanyprogeny,thatwhencomplete,leavethehostcelltoinfectothercellsintheorganism.

    Virusesmaycontaindouble-strandedDNA,double-stranded

    RNA,single-strandedDNAorsingle-strandedRNA.Thetype

    ofgeneticmaterialfoundinaparticularvirusdependson

    thenatureandfunctionofthespecificvirus.Theexact

    natureofwhathappensafterahostisinfectedvaries

    dependingonthenatureofthevirus.Theprocessfor

    double-strandedDNA,single-strandedDNA,double-strandedRNAandsingle-strandedRNAviralreplicationwill

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    differ.Forexample,double-strandedDNAvirusestypically

    mustenterthehostcell'snucleusbeforetheycanreplicate.

    Single-strandedRNAviruseshowever,replicatemainlyin

    thehostcell'scytoplasm.

    Onceavirusinfectsitshostandtheviralprogeny

    componentsareproducedbythehost'scellularmachinery,

    theassemblyoftheviralcapsidisanon-enzymaticprocess.

    Itisusuallyspontaneous.Virusestypicallycanonlyinfecta

    limitednumberofhosts(alsoknownashostrange).The

    "lockandkey"mechanismisthemostcommonexplanation

    forthisrange.Certainproteinsonthevirusparticlemustfitcertainreceptorsitesontheparticularhost'scellsurface.

    HowVirusesInfectCells

    Thebasicprocessofviralinfectionandvirusreplication

    occursin6mainsteps.

    1.Adsorption-virusbindstothehostcell.2.Penetration-virusinjectsitsgenomeintohostcell.

    3.ViralGenomeReplication-viralgenomereplicatesusingthehost'scellularmachinery.

    4.Assembly-viralcomponentsandenzymesareproducedandbegintoassemble.

    5.Maturation-viralcomponentsassembleandvirusesfullydevelop.

    6.Release-newlyproducedvirusesareexpelledfromthehostcell.

    Virusesmayinfectanytypeofcellincludinganimalcells,

    plantcellsandbacterialcells.Toviewanexampleofthe

    processofviralinfectionandvirusreplication,seeVirus

    Replication:Bacteriophage.Youwilldiscoverhowa

    bacteriophage,avirusthatinfectsbacteria,replicatesafterinfectingabacterialcell.

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    AmendmentstotheCentralDogma

    Icouldnotfindanythingaboutthis,theonlyinterestingandfaithfully

    informationaboutthedogmaarethoseprocessesnotstatedbyitselfbutstill

    trueintherealpractice:

    ReversetranscriptionisthetransferofinformationfromRNAtoDNA(thereverseofnormal

    transcription).

    RNAreplicationisthecopyingofoneRNAtoanother.Manyvirusesreplicatethisway.

    DirecttranslationfromDNAtoproteinhasbeen

    demonstratedinacell-freesystem(i.e.inatesttube),

    usingextractsfromE.colithatcontainedribosomes.

    VariationinmethylationstatesofDNAcanaltergeneexpressionlevelssignificantly.

    Prionsareproteinsthatpropagatethemselvesbymakingconformationalchangesinothermoleculesof

    thesametypeofprotein.

    ImsureIcouldnotreachtheendoftheentireworkthistimebutasthelast

    one,IhopeitwouldbehelpfulforYouguys

    Yourbelovedandtiredandcrazyandemotionalandcomplicatedandlazyand

    excitedandstrangeandprettyandadorablecolleague,

    AlessandroMotta

    PS:itwillbemorecomplicatedthanwhatwecanthink,iftheresahellbelow.Weareallgonnago!