Chapter 16 molecular inheritance
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Chapter 16 molecular inheritance Chapter 16 molecular inheritance Presentation Transcript

  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsPowerPoint Lectures forBiology, Seventh EditionNeil Campbell and Jane ReeceLectures by Chris RomeroChapter 16The Molecular Basis ofInheritance
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Overview: Life’s Operating Instructions• In 1953, James Watson and Francis Crickshook the world– With an elegant double-helical model for thestructure of deoxyribonucleic acid, or DNAFigure 16.1
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• DNA, the substance of inheritance– Is the most celebrated molecule of our time• Hereditary information– Is encoded in the chemical language of DNAand reproduced in all the cells of your body• It is the DNA program– That directs the development of many differenttypes of traits
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Concept 16.1: DNA is the genetic material• Early in the 20th century– The identification of the molecules ofinheritance loomed as a major challenge tobiologists
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsThe Search for the Genetic Material: Scientific Inquiry• The role of DNA in heredity– Was first worked out by studying bacteria andthe viruses that infect them
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsEvidence That DNA Can Transform Bacteria• Frederick Griffith was studying Streptococcuspneumoniae– A bacterium that causes pneumonia inmammals• He worked with two strains of the bacterium– A pathogenic strain and a nonpathogenicstrain
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Griffith found that when he mixed heat-killedremains of the pathogenic strain– With living cells of the nonpathogenic strain,some of these living cells became pathogenicBacteria of the “S” (smooth) strain of Streptococcus pneumoniae are pathogenic because theyhave a capsule that protects them from an animal’s defense system. Bacteria of the “R” (rough) strain lack a capsuleand are nonpathogenic. Frederick Griffith injected mice with the two strains as shown below:Griffith concluded that the living R bacteria had been transformed into pathogenic S bacteria by anunknown, heritable substance from the dead S cells.EXPERIMENTRESULTSCONCLUSIONLiving S(control) cellsLiving R(control) cellsHeat-killed(control) S cellsMixture of heat-killed S cellsand living R cellsMouse dies Mouse healthy Mouse healthy Mouse diesLiving S cellsare found inblood sample.Figure 16.2
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Griffith called the phenomenon transformation– Now defined as a change in genotype andphenotype due to the assimilation of externalDNA by a cell
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsEvidence That Viral DNA Can Program Cells• Additional evidence for DNA as the geneticmaterial– Came from studies of a virus that infectsbacteria
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Viruses that infect bacteria, bacteriophages– Are widely used as tools by researchers inmolecular geneticsFigure 16.3PhageheadTailTail fiberDNABacterialcell100nm
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Alfred Hershey and Martha Chase– Performed experiments showing that DNA isthe genetic material of a phage known as T2
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• The Hershey and Chase experimentIn their famous 1952 experiment, Alfred Hershey and Martha Chase used radioactive sulfurand phosphorus to trace the fates of the protein and DNA, respectively, of T2 phages that infected bacterial cells.Radioactivity(phage protein)in liquidPhageBacterial cellRadioactiveproteinEmptyprotein shellPhageDNADNACentrifugePellet (bacterialcells and contents)RadioactiveDNACentrifugePelletBatch 1: Phages weregrown with radioactivesulfur (35S), which wasincorporated into phageprotein (pink).Batch 2: Phages weregrown with radioactivephosphorus (32P), whichwas incorporated intophage DNA (blue).1 2 3 4Agitated in a blender toseparate phages outsidethe bacteria from thebacterial cells.Mixed radioactivelylabeled phages withbacteria. The phagesinfected the bacterial cells.Centrifuged the mixtureso that bacteria formeda pellet at the bottom ofthe test tube.Measured theradioactivity inthe pellet andthe liquidPhage proteins remained outside the bacterial cells during infection, while phage DNA entered the cells.When cultured, bacterial cells with radioactive phage DNA released new phages with some radioactive phosphorus.Hershey and Chase concluded that DNA, not protein, functions as the T2 phage’s genetic material.RESULTSCONCLUSIONEXPERIMENTRadioactivity(phage DNA)in pelletFigure 16.4
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsAdditional Evidence That DNA Is the Genetic Materia• Prior to the 1950s, it was already known that DNA– Is a polymer of nucleotides, each consisting ofthree components: a nitrogenous base, asugar, and a phosphate groupSugar-phosphatebackboneNitrogenousbases5 endO–O P O CH254O–HHOHHH31H OCH3NONHThymine (T)OO P OO–CH2HHOHHHHNNNHNHHAdenine (A)OO P OO–CH2HHOHHHHH HHNNNOCytosine (C)OO P O CH254O–HOHH31OH2HNNN HONN HHH HSugar (deoxyribose)3 endPhosphateGuanine (G)DNA nucleotide2NFigure 16.5
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Erwin Chargaff analyzed the base composition of DNA– From a number of different organisms• In 1947, Chargaff reported– That DNA composition varies from one species tothe next• This evidence of molecular diversity among species– Made DNA a more credible candidate for the geneticmaterial
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsBuilding a Structural Model of DNA: Scientific Inquiry• Once most biologists were convinced that DNAwas the genetic material– The challenge was to determine how thestructure of DNA could account for its role ininheritance
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Maurice Wilkins and Rosalind Franklin– Were using a technique called X-raycrystallography to study molecular structure• Rosalind Franklin– Produced a picture of the DNA molecule usingthis technique(a) Rosalind Franklin Franklin’s X-ray diffractionPhotograph of DNA(b)Figure 16.6 a, b
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsFigure 16.7a, cCTAATCGGCAC GATATA TTACTA0.34 nm3.4 nm(a) Key features of DNA structureG1 nmG(c) Space-filling modelT• Watson and Crick deduced that DNA was adouble helix– Through observations of the X-raycrystallographic images of DNA
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Franklin had concluded that DNA– Was composed of two antiparallel sugar-phosphate backbones, with the nitrogenousbases paired in the molecule’s interior• The nitrogenous bases– Are paired in specific combinations: adeninewith thymine, and cytosine with guanine
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsO–O OOHO–OOOH2CO–OOOH2CO–OOOOHOOOT ACGCA TOOOCH2OO–OOCH2CH2CH25 endHydrogen bond3 end3 endGPPPPOOHO–OOOPPO–OOOPO–OOOP(b) Partial chemical structureH2C5 endFigure 16.7bO
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Watson and Crick reasoned that there must beadditional specificity of pairing– Dictated by the structure of the bases• Each base pair forms a different number ofhydrogen bonds– Adenine and thymine form two bonds,cytosine and guanine form three bonds
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsN H O CH3NNONNNN HSugarSugarAdenine (A) Thymine (T)NNNNSugarO H NHNHN OHHNSugarGuanine (G) Cytosine (C)Figure 16.8H
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Concept 16.2: Many proteins work together inDNA replication and repair• The relationship between structure andfunction– Is manifest in the double helix
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsThe Basic Principle: Base Pairing to a Template Strand• Since the two strands of DNA arecomplementary– Each strand acts as a template for building anew strand in replication
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• In DNA replication– The parent molecule unwinds, and two newdaughter strands are built based on base-pairing rules(a) The parent molecule has twocomplementary strands of DNA.Each base is paired by hydrogenbonding with its specific partner,A with T and G with C.(b) The first step in replication isseparation of the two DNAstrands.(c) Each parental strand nowserves as a template thatdetermines the order ofnucleotides along a new,complementary strand.(d) The nucleotides are connectedto form the sugar-phosphatebackbones of the new strands.Each “daughter” DNAmolecule consists of one parentalstrand and one new strand.ACTAGACTAGACTAGACTAGTGATCTGATCACTAGACTAGTGATCTGATCTGATCTGATCFigure 16.9 a–d
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsFigure 16.10 a–cConservativemodel. The twoparental strandsreassociateafter acting astemplates fornew strands,thus restoringthe parentaldouble helix.Semiconservativemodel. The twostrands of theparental moleculeseparate,and each functionsas a templatefor synthesis ofa new, comple-mentary strand.Dispersivemodel. Eachstrand of bothdaughter mol-ecules containsa mixture ofold and newlysynthesizedDNA.Parent cellFirstreplicationSecondreplication• DNA replication is semiconservative– Each of the two new daughter molecules willhave one old strand, derived from the parentmolecule, and one newly made strand(a)(b)(c)
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Experiments performed by Meselson and Stahl– Supported the semiconservative model of DNAreplicationFigure 16.11Matthew Meselson and Franklin Stahl cultured E. coli bacteria for several generationson a medium containing nucleotide precursors labeled with a heavy isotope of nitrogen, 15N. The bacteriaincorporated the heavy nitrogen into their DNA. The scientists then transferred the bacteria to a medium withonly 14N, the lighter, more common isotope of nitrogen. Any new DNA that the bacteria synthesized would belighter than the parental DNA made in the 15N medium. Meselson and Stahl could distinguish DNA of differentdensities by centrifuging DNA extracted from the bacteria.EXPERIMENTThe bands in these two centrifuge tubes represent the results of centrifuging two DNA samples from the flaskin step 2, one sample taken after 20 minutes and one after 40 minutes.RESULTSBacteriacultured inmediumcontaining15NBacteriatransferred tomediumcontaining14N21DNA samplecentrifugedafter 20 min(after firstreplication)3 DNA samplecentrifugedafter 40 min(after secondreplication)4LessdenseMoredense
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsCONCLUSION Meselson and Stahl concluded that DNA replication follows the semiconservativemodel by comparing their result to the results predicted by each of the three models in Figure 16.10.The first replication in the 14N medium produced a band of hybrid (15N–14N) DNA. This result eliminatedthe conservative model. A second replication produced both light and hybrid DNA, a result that eliminatedthe dispersive model and supported the semiconservative model.First replication Second replicationConservativemodelSemiconservativemodelDispersivemodel
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsDNA Replication: A Closer Look• The copying of DNA– Is remarkable in its speed and accuracy• More than a dozen enzymes and other proteins– Participate in DNA replication
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsGetting Started: Origins of Replication• The replication of a DNA molecule– Begins at special sites called origins ofreplication, where the two strands areseparated
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• A eukaryotic chromosome– May have hundreds or even thousands ofreplication originsReplication begins at specific siteswhere the two parental strandsseparate and form replicationbubbles.The bubbles expand laterally, asDNA replication proceeds in bothdirections.Eventually, the replicationbubbles fuse, and synthesis ofthe daughter strands iscomplete.123Origin of replicationBubbleParental (template) strandDaughter (new) strandReplication forkTwo daughter DNA moleculesIn eukaryotes, DNA replication begins at many sites along the giantDNA molecule of each chromosome.In this micrograph, three replicationbubbles are visible along the DNA ofa cultured Chinese hamster cell (TEM).(b)(a)0.25 µmFigure 16.12 a, b
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsFigure 16.13New strand Template strand5 end 3 endSugar A TBaseCGGCACTPPPOHP P5 end 3 end5 end 5 endA TCGGCACT3 endPyrophosphate2 POHPhosphateElongating a New DNA Strand• Elongation of new DNA at a replication fork– Is catalyzed by enzymes called DNApolymerases, which add nucleotides to the 3′end of a growing strandNucleosidetriphosphate
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsAntiparallel Elongation• How does the antiparallel structure of thedouble helix affect replication?
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• DNA polymerases add nucleotides– Only to the free 3′ end of a growing strand• Along one template strand of DNA, the leadingstrand– DNA polymerase III can synthesize acomplementary strand continuously, movingtoward the replication fork
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• To elongate the other new strand of DNA, thelagging strand– DNA polymerase III must work in the directionaway from the replication fork• The lagging strand– Is synthesized as a series of segments calledOkazaki fragments, which are then joinedtogether by DNA ligase
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsParental DNADNA pol Ill elongatesDNA strands only in the5 3 direction.1OkazakifragmentsDNA pol IIITemplatestrandLagging strand32Templatestrand DNA ligaseOverall direction of replicationOne new strand, the leading strand,can elongate continuously 5 3as the replication fork progresses.2The other new strand, thelagging strand must grow in an overall3 5 direction by addition of shortsegments, Okazaki fragments, that grow5 3 (numbered here in the orderthey were made).3DNA ligase joins Okazakifragments by forming a bond betweentheir free ends. This results in acontinuous strand.4Figure 16.1435533521Leading strand1• Synthesis of leading and lagging strandsduring DNA replication
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsPriming DNA Synthesis• DNA polymerases cannot initiate the synthesisof a polynucleotide– They can only add nucleotides to the 3′ end• The initial nucleotide strand– Is an RNA or DNA primer
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Only one primer is needed for synthesis of theleading strand– But for synthesis of the lagging strand, eachOkazaki fragment must be primed separately
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsOverall direction of replication333353535353535353 55112112551235TemplatestrandRNA primerOkazakifragmentFigure 16.15Primase joins RNA nucleotidesinto a primer.1DNA pol III adds DNA nucleotides to theprimer, forming an Okazaki fragment.2After reaching the nextRNA primer (not shown),DNA pol III falls off.3After the second fragment isprimed. DNA pol III adds DNAnucleotides until it reaches thefirst primer and falls off.4DNA pol 1 replaces theRNA with DNA, adding tothe 3 end of fragment 2.5DNA ligase forms a bondbetween the newest DNAand the adjacent DNA offragment 1.6 The lagging strandin this region is nowcomplete.7
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsOther Proteins That Assist DNA Replication• Helicase, topoisomerase, single-strand bindingprotein– Are all proteins that assist DNA replicationTable 16.1
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsFigure 16.16Overall direction of replicationLeadingstrandLaggingstrandLaggingstrandLeadingstrandOVERVIEWLeadingstrandReplication forkDNA pol IIIPrimasePrimerDNA pol III LaggingstrandDNA pol IParental DNA53432Origin of replicationDNA ligase153Helicase unwinds theparental double helix.1Molecules of single-strand binding proteinstabilize the unwoundtemplate strands.2 The leading strand issynthesized continuously in the5 3 direction by DNA pol III.3Primase begins synthesisof RNA primer for fifthOkazaki fragment.4DNA pol III is completing synthesis ofthe fourth fragment, when it reaches theRNA primer on the third fragment, it willdissociate, move to the replication fork,and add DNA nucleotides to the 3 endof the fifth fragment primer.5 DNA pol I removes the primer from the 5 endof the second fragment, replacing it with DNAnucleotides that it adds one by one to the 3 endof the third fragment. The replacement of thelast RNA nucleotide with DNA leaves the sugar-phosphate backbone with a free 3 end.6 DNA ligase bondsthe 3 end of thesecond fragment tothe 5 end of the firstfragment.7• A summary of DNA replication
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsThe DNA Replication Machine as a Stationary Complex• The various proteins that participate in DNAreplication– Form a single large complex, a DNAreplication “machine”• The DNA replication machine– Is probably stationary during the replicationprocess
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsProofreading and Repairing DNA• DNA polymerases proofread newly made DNA– Replacing any incorrect nucleotides• In mismatch repair of DNA– Repair enzymes correct errors in base pairing
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsFigure 16.17NucleaseDNApolymeraseDNAligaseA thymine dimerdistorts the DNA molecule.1A nuclease enzyme cutsthe damaged DNA strandat two points and thedamaged section isremoved.2Repair synthesis bya DNA polymerasefills in the missingnucleotides.3DNA ligase seals theFree end of the new DNATo the old DNA, making thestrand complete.4• In nucleotide excision repair– Enzymes cut out and replace damagedstretches of DNA
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsReplicating the Ends of DNA Molecules• The ends of eukaryotic chromosomal DNA– Get shorter with each round of replicationFigure 16.18End of parentalDNA strandsLeading strandLagging strandLast fragment Previous fragmentRNA primerLagging strandRemoval of primers andreplacement with DNAwhere a 3 end is availablePrimer removed butcannot be replacedwith DNA becauseno 3 end availablefor DNA polymeraseSecond roundof replicationNew leading strandNew lagging strand 5Further roundsof replicationShorter and shorterdaughter molecules535353533
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Eukaryotic chromosomal DNA molecules– Have at their ends nucleotide sequences,called telomeres, that postpone the erosion ofgenes near the ends of DNA moleculesFigure 16.19 1 µm
  • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• If the chromosomes of germ cells becameshorter in every cell cycle– Essential genes would eventually be missingfrom the gametes they produce• An enzyme called telomerase– Catalyzes the lengthening of telomeres ingerm cells