Tips%for%how%to%do%well%in%class1) Eat breakfast.2) Read the chapter one to two days before the lecture, trying toexplain the material to yourself.3) Close the book and without referring to notes, “teach” the material toyourself, a friend or an imaginary audience.4) Make notes on things that you don’t understand and listen to usexplain it in class.5) Listen in class.6) If you still don’t understand a concept, ask a question in class!7) After the lecture, “teach” the material to yourself again to solidifywhat you learned in the book and lecture.8) Do the problems in the book before looking at the answers.9) Be able to do the “Be able to” items at the end of lectures!Chapter 5DNA and ChromosomesThis is the core of-biotechnology (medicine and agriculture)-Human, animal, crop, and research genetics- genetic counseling-molecular medicine-Most of the biology classes you will be taking after 213Objectives• Understand the key experiments that led tothe conclusion that DNA is the geneticmaterial• Understand the relationship between thestructure of DNA and its function in heredity• Understand the organization of DNA intochromatin and chromosomesBe%able%to:•Write'a'complementary'DNA'strand,'labeling'3’and'5’,'given'asingle'strand'sequence•Describe,'explain,'and'sketch'the'Avery/'MacLeod/'McCartyexperiment•Predict'the'outcome'of'the'A/M/M'experiment'if'geneGcinformaGon'was'protein'or'RNA•Describe,'explain,'and'sketch'the'HersheyKChase'experiment•Design'two'experiments'to'determine'what'the'carrier'of'geneGcinformaGon'is'in'a'new'organism'that'infects'human'cells•Sketch'the'Central'Dogma,'naming'the'molecules'and'processes•Compare'DNA'compacGon'in'eukaryotes'and'prokaryotes•Sketch'the'arrangement'of'DNA'on'histo nes•Predict'the'effect'of'histone'modificaGons'(that'affect'histonecharge)'on'how'Gghtly'the'histone'binds'to'DNA,'and'be'able'todefend'your'answer05_02_DNA.jpgChemical basis of genesFirst key experiment leading to identification ofDNA as genetic material, and example of howwork in one field can lead to a breakthrough in adifferent field• 1928: Frederick Griffith, studying pneumococcuspathogenicity, showed that material could betransferred from a heat-killed virulent strain to anon-virulent strain, making the non-virulent strainvirulent• This process was called transformation05_03_Griffith.jpgGriffith’sdemonstration oftransformationAvery, MacLeod andMcCarty demonstrate thatDNA is the transformingprincipleKey idea: A mixture of thingshas an effect on something.Separate the components,see which one has the effect.Key idea #2: A mixture ofthings has an effect onsomething. Deletecomponents one by one, seewhich deletion cause theeffect to disappear.Use enzymes thatdestroy specificcomponentsEnzyme-treated mixtures tested for transformation of R-strain cellsRNase protease DNase lipase amylaseAvery, MacLeod andMcCarty demonstrate thatDNA is the transformingprinciple• Some phage viruses contain just DNA and protein,when they infect bacteria, the bacteria make moreviruses, so something in the virus has geneticinformation• Electron microscopy showed that the virusattaches to the bacteria, and injects something intoit• Label phage DNA with 32P and phage proteins with35S, then infect bacteria, let the ‘injection’ occur,then tear off the virus and see what got injectedinto the bacteria….Many scientists still did not believe that DNA wasthe carrier of genetic information05_05_Hershey_Chase.jpgHershey-ChaseExperimentComplementary Base PairingChargaff’s Rule• Erwin Chargaff showed that base compositionvaried significantly from species to species• Furthermore, it did not matter from which tissueor organ the DNA came from. Basecomposition was constant within the species.• Most importantly, A=T and G=C, that is A and Twere present in equimolar amounts as were Gand C, and A+T ≠ G+C Chargaff’s RuleThe Structure of DNA1953: Watson andCrick used molecularmodels based on X-raydiffraction data fromRosalind Franklin andMaurice Wilkins topropose a doublehelical structure forDNA where the helixwas held together byA-T and G-C basepairs.Properties of the DNA Double Helix• Two DNA strandswrapped in a right-handed helix• The two chains areantiparallel• Sugar-phosphatebackbone on theoutside, bases projecttoward the center• The bases are stackedone on top of the other(hydrophobicinteractions and van derWaals forces stabilizethe helix)05_06_compl_pairs.jpgComplementary base pairsComplementary Base Pairing• Purine/Pyrimidine base pairs• A base pairs with T– Two hydrogen bonds– Less stable than G-C base pairs• G base pairs with C– Three hydrogen bonds– More stable than A-T base pairsProperties of the DNA Double Helix• Hydrogen bonds between thebases contribute to helicalstability• The helix diameter is uniformbecause A/T and G/C base pairshave identical widths• 10 bases per helical turn• Spaces between the turns of thehelix forms major and minorgrooves - important sites forDNA/protein interactions• Complementarity- nucleotideson one chain are complementaryto nucleotides on the other strandImplications of theWatson-Crick Model• Linear arrangement of nucleotides could store thegenetic information• Complementarity provided a mechanism forreplication of the genetic information• How the genetic information was expressed,however, was a complete mystery– But the stage was set to pursue these questions“Central Dogma” of Molecular Biology• Genome = The total DNA complement of anorganism• In general, the more complex an organism, thelarger its genome.• The complete genomes of a number oforganisms, including humans, have beensequenced.• Bioinformatics tools are now used to identifyand count genes in sequenced genomesComplete set of information in an organism’s DNAGenomic DNA is packagedinto chromosomesHuman karyotypeChromosomes are verylong, single DNAmolecules associated withproteins that fold andpack the DNA into acompact structure(10,000-fold compaction)The complex of DNA andassociated proteins iscalled chromatin05_17_cell cycle.jpgThe organization of DNA inchromosomes must be dynamicReview mitosis on your ownInterphase chromosomes are organized within the nucleusThe DNA of interphasechromosomes is 1000-fold less compact thanin metaphasechromosomesNucleosomes are the basic units ofeukaryotic chromatin structureBacteria don’t have nucleosomes - they have a bigpiece of circular DNA that is