Week%208-24 - What is Molecular Biology? • arose from...

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Unformatted text preview: What is Molecular Biology? • arose from genetics, biochemistry, and anatomical cell biology. • studies the structure, function, and behavior of the biological macromolecules (nucleic acids and proteins). Why study Molecular Biology? Molecular Biology-BISC 320L Fall, 2009 Lectures are in THH 101: MWF 11:00AM-11:50 a.m., and MWF 12:00 PM-12:50 p.m. Faculty: Oscar Aparicio, Ph.D., Associate Professor (oaparici@usc.edu), Robert Baker, Ph.D., Professor (baker@usc.edu), Xuelin Wu, Ph.D., Assistant Professor (xuelinwu@usc.edu), Pamela Lum, Ph.D., Instructional Lab Manager (pamlum@usc.edu) Office hours: Aparicio: Fridays 2:30-4:30 PM in RRI 221, starting 10/2/09 Baker: M ondays 1:45-3:30 PM in RRI 121, starting 11/2/09 Wu: Fridays 2:30-4:30 PM in RRI 221, starting 8/28/09 Textbook: Molecular Biology of the Gene, Watson et al., 6th ed. Readings from these texts are assigned on the lecture schedule. It is important to read the assignments prior to the corresponding lectures. Date 8/248/28 8/319 /4 9/99/11 9/149/18 9/219/23 9 /25 Reading assignment Chap 1 & Chap 2 pp 19-28 Prof. Wu begins lecturing Chap 2 pp 28-41, Chas 3 pp 45-46, Chap 4, Chap 5 pp 525-538 Chap 5, Chap 21 pp 764-771 Chap 6, Chap 21 pp740-750 Chap 7 pp 157-192 Topics covered Review and introduction: Mendelian genetics; classic experiments that revealed the nature of genes. Central Dogma. Biochemical bonds and interactions. Amino acids and Protein structures. DNA structure, DNA binding proteins, DNA topology, RNA structure, Genome Structure, Chromatin and the Nucleosome 9/2810/2 10/510/9 10/12 Chap 10. 10/16 10/19 Chap 11 10/23 1 0/26 Midterm 2. You must take the midterm in the lecture period in which you are registere d . 10/28 Chap 12 and 13 Baker begins lecturing 11/2 11/4- Chap 13 and 14 11/9 11/11 Chap 14 and 15 11/13 11/16 Chap 16 and pp 638-640; Chap 17 11/20 11/23 Chap 17 11/25 11/30 Chap 18 and pp 626-629, 801, 816-817 -12/4 12/10 Final Exam- Wed, 12/9 11AM for 11AM class or -Fri, 12/11 at 11AM for the noon class 12/12 You must take the final exam at the time scheduled for your registered lecture section Midterm 1. You must take each midterm in the lecture period in which you are registere d . Chap 8 DNA replication Regulation of DNA replication Prof. Aparicio begins lecturing Chap 9 DNA mutations and DNA repair. Homologous recombination. Molecular Genetics Site-specific recombination Mechanisms of transcription and RNA splicing RNA splicing and editing, translation Translation, genetic code, wobble, suppression Gene regulation in prokaryotes and eukaryotes Gene regulation in eukaryotes Regulatory RNAs, epigenetics, applications to medicine and biotechnology Cumulative, with emphasis on material not covered on the midterms. The course grade will be based upon 700 possible points: 125 pts midterm #1 125 pts midterm #2 200 pts lab 250 pts final exam (cumulative) In case a midterm exam must be missed for legitimate reasons, discuss the situation with the course instructor prior to the exam if possible. Rules governing exams are given in more detail in your Student Contract, which is also posted on the class website: https://blackboard.usc.edu Lab Sections: Please see separate syllabus and lab manual. There will be no lab meetings the first week of classes. The lecture slides (Aparicio, Wu) and summaries (Baker), posted on the course Blackboard internet site (https://blackboard.usc.edu, may contain material that is not in the lectures—and the lectures may contain information that is not conveyed in the Blackboard lecture summaries. The lecture summaries, as posted on Blackboard, and the textbook are intended to be helpful, but auxiliary to the lectures. SI sections: Students with disabilities: Students requesting academic accommodations based on a disability are required to register with Disability Services and Programs (DSP) each semester. A letter of verification for approved accommodations can be obtained from DSP when adequate documentation is filed. Please be sure the letter is delivered to Dr. Lum as early in the semester as possible. DSP is open Monday-Friday, 8:30 to 5:00, (213) 740-0776. How to do well in this class? • Attend all the lectures and take good notes. • Read the assigned materials before lecture. • the “how” v.s. the “why” Academic Integrity General principles of academic honesty include the concept of respect for the intellectual property of others, the expectation that individual work will be submitted unless otherwise allowed by an instructor, and the obligations both to protect one’s own academic work from misuse by others as well as to avoid using another’s work as one’s own. All students are expected to understand and abide by these principles. Scampus, the Student Guidebook, contains the Student Conduct Code in Section 11.00, while the recommended sanctions are located in Appendix A: http://www.usc.edu/dept/publications/SCAMPUS/gov/. Students will be referred to the Office of Student Judicial Affairs and Community Standards for further review, should there be any suspicion of academic dishonesty. The Review process can be found at: http://www.usc.edu/student-affairs/SJACS/. A brief history of Molecular Biology Outline • Mendelian genetics • Chromosomal theory of heredity • The nature of gene Reading assignments: Molecular Biology of the Gene (Watson, 6th ed) chapter 1, chapter 2, page 19-28. Definitions: • • • • • • gene: the basic biological unit of heredity. allele: different versions of the same gene. genotype: an individual’s genetic composition. phenotype: an individual’s visible trait. homozygous: a genotype that has an identical pair of alleles. heterozygous: a genotype that has two different alleles for the gene. Mendel’s breeding experiments 34 true-breeding strains >21,000 hybrid plants Results published in 1865. Mendel’s 1st Law: Independent Segregation (of alleles) • individual’s phenotypes were determined by a pair of “particulate factors” (alleles) • Alleles may be dominant (the trait seen in F1) or recessive (the trait not seen in F1). • Individual alleles segregate independently into gametes. • Each gamete receives one allele from each pair. Mendel’s 1st law does not require one allele to be dominant • For many alleles, the heterozygous phenotype is different from both homozygous phenotypes. • The resulting phenotype may be intermediate to the homozygous. This is incomplete dominance. Mendel’s 2nd Law: Independent Assortment (of genes) • Different genes independently sort into gametes. • Each gamete receives one allele of each gene. The Chromosomal Theory of Inheritance Walter Sutton, 1903 “many points were discovered which strongly indicate that the position of the bivalent chromosomes in the equatorial plate of the reducing division is purely a matter of chance—that is, that any chromosome pair may lie with maternal or paternal chromatid indifferently toward either pole irrespective if the positions of other pairs, --and hence that a large number of different combinations of maternal and paternal chromosomes are possible in the mature germ-products of the individual” Mitosis • Occurs in dividing somatic cells • Chromosome replication: exact duplicates = sister chromatids attached at centromere Meiosis • only in reproductive cells = germ cells • Two rounds of cell division result in the formation of gametes which are genetically haploid = contain only one copy of each pair of homologous chromosomes The Chromosomal Theory of Inheritance • Diploid cells have two morphologically similar sets of chromosomes and each haploid gamete received one set. • Each gamete gets a random combination of chromosomes. • Hypothesized that genes reside on chromosomes, with one allele on each homologous chromosome. Discovery of sex-linked genes Thomas Morgan & colleagues, ~1910 All genes do not assort independently Inconsistencies with Mendel’s 2nd law: 1. Number of genes >>> number of chromosomes 2. many genes studied did not assort independently of each other (linked to each other). Linkage between genes occurs because the genes are located on the same chromosome --- linkage group. Cross-over --- Janssens’ “partial chiasmatypy” hypothesis, 1924 Linked genes segregate into different gametes at frequencies varying from almost 0% (complete linkage) to almost 50% (unlinked). Proof of recombination between homologous chromosomes Barbara McClintock & Harriet Creighton, 1931 Recombination Frequency Measures the Distance between Linked Genes • The likelihood of a recombination event between linked genes increases with increasing distance between the genes. • The distances between genes are given as genetic map units: 10% recombination equals 10 map units. A Three-Factor Cross Determines The Physical Order of Genes The Genetic Map of Chromosome 2 of Drosophila melanogaster Gene function can change via mutation • spontaneous mutation • induced mutation (Muller & Stadler, 1927) Gene size can be estimated by X-ray induced mutation rate. What is a gene made of? chromosome protein nucleic acid (DNA) A gene needs to be self-replicating. Genes control enzyme functions • 1902, Archibald Garrod proposed that alkaptonuria (failure in metabolize tyrosine) is caused by a rare Mendelian factor. • Muriel Wheldale & Rose Scott-Moncrief studied plant anthocyanins synthesis. • Fritz von Wettstein studied eye color in butterfly. • Boris Ephrussi & George Beadle studied eye color in Drosophila. • 1941, George Beadle & Edward Tatum described the tryptophan biosynthetic pathway, and showed that each step was controlled by a different gene. The one gene - one enzyme hypothesis • All biochemical processes in all living organisms are under genetic control. •All biochemical reactions in an organism are resolvable into separate steps. •Each step or reaction is under the control of a single gene. •Mutation of a single gene results in the loss of function of the appropriate enzyme. Griffith Identified the “Transforming Principle”1928 • A substance in the virulent S. pneumoniae strain transformed a non-virulent strain of S. pneumoniae into a virulent strain. Transformation Is The Transfer of Genetic Material into Bacteria The Transforming Material Was Associated with DNA Avery, MacLeod and McCarty (1944) • Heat-killed “S” strains were fractionated into their chemical constituents, and each fraction was tested for the ability to transform “R” strains into “S” strains. • The DNA fraction is responsible for transformation. Further Evidence That the Transforming Material Was DNA • Neither various proteases (to destroy possible contaminating proteins) nor ribonuclease (to destroy contaminating RNA) can eliminated transformation by the DNA fraction. • deoxyribonuclease (DNase) treatment eliminated transformation. The Life Cycle of Lytic Bacteriophage • Phages are bacterial viruses. • Phage are composed of protein and DNA (or RNA) only. DNA Is The Genetic Material Hershey and Chase, 1952 Most of the 32P was found to enter the bacteria (as well as progeny phage!), while 35S remained associated with the phage ghosts. The Nucleotides of DNA A nucleotide is a ribose linked to one base (adenine, cytosine, guanine, and thymine) and one phosphate. The Proposed Tetranucleotide Structure of DNA DNA has a simple chemical composition: deoxyribose, phosphate, and one of four base groups. The tetranucleotide structure of DNA predicted equal quantities of each base. Chargaff’s rules (1949) DNA of different species have different nucleotide composition with the following rules: 1)The amounts of A=T and G=C 2)The amount of A+G=C+T 3)The amount of A+T did not necessarily equal the amount of G+C, but varied among different species. 3’ to 5’ Phosphodiester Bonds Join Nucleotides in DNA (1952) • Nucleotides are joined through phosphate groups to form a phosphodiester bond. The ribose and phosphates form a chain or backbone with the bases branching off. • Rosalind Franklin and her X-ray diffraction photo of DNA (1952) Watson and Crick Revealed The Double Helical Structure of DNA (1953) • Two DNA chains are held together by hydrogen bonds between pairs of bases on opposite strands. Base-pairing is specific: A pairs only with T, G pairs only with C. The nucleotide sequence of one strand defines the sequence of the other strand (complementary). This structure implied that one strand could serve as a template for the copying (replication) of DNA. • • • DNA polymerase I can synthesize new DNA (Arthur Kornberg, 1956) • • • Precursors are deoxyribonucleotide triphosphates (dNTPs); Requires a DNA template; the newly synthesized DNA molecules had a similar base composition as the template --- replication. Three Models for the Replication of DNA DNA Replication Is Semi-Conservative (Messelson and Stahl, 1958) HH mix HL HH + HL DNA is the genetic material ...
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This note was uploaded on 10/20/2009 for the course BISC 320L taught by Professor Baker,aparicio during the Spring '07 term at USC.

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