biology review1
TRANSCRIPT
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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!