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Wheeler High School The Center for Advanced Studies in Science, Math & Technology Course Introduction Genetics Lecture 1 Post-AP DNA/Genetics – Mrs. Kelavkar What Is A Gene? • We shall begin with the physical definition of a gene. Conceptually, this is quite simple and gives us a chance to refresh our minds. Post-AP DNA/Genetics – Mrs. Kelavkar • Genes are made of DNA Watson & Crick • 1953 • Deduced structure of DNA as double helix – With a little help from Rosalind Franklin • Complementary base pairing (Chargaff) – Showed how information could be encoded in a molecule & duplicated • Thus REPLICATION Post-AP DNA/Genetics – Mrs. Kelavkar Gene Expression: From DNA to Phenotype • TRANSCRIPTION – Uses complementary base pairing – Makes mRNA • RNA is chemically less stable than DNA • Think of mRNA as a temporary molecule that stores DNA’s information Post-AP DNA/Genetics – Mrs. Kelavkar Initiation of Transcription Transcription begins at the 5’ end of the gene in a region called the promoter. The promoter recruits TATA protein, a DNA binding protein, which in turn recruits other proteins. TATA binding protein Promoter DNA GG Transcription factor Gene sequence to be transcribed TATA TATA box Transcription begins When a complete transcription complex is formed RNA polymerase binds and transcription begins. Translation The process of reading the RNA sequence of an mRNA and creating the amino acid sequence of a protein is called translation. DNA Transcription T T C A G T C A G A A G U C A G U C DNA template strand Messenger RNA mRNA Codon Codon Codon Translation Protein Lysine Serine Valine Polypeptide (amino acid sequence) Make me a protein! (Remember…”Structure equals function”) You see… it’s all about the proteins. Cellular processes depends on protein structure AND the amino acid combinations that make them! Having Said That… What is a GENE? A DNA segment that is needed to make a protein. Post-AP DNA/Genetics – Mrs. Kelavkar Genes • Usually 103 – 104 bp in size – Human dystrophin gene is 2 x 106 bp • Connects muscle fibers to cell membrane • E. coli has ~4,200 genes – Not very many – There are more than 1,000 different enzymes needed to carry out the necessary biological reactions in an E. coli cell Post-AP DNA/Genetics – Mrs. Kelavkar Dystrophin Connects the muscle fibers to the cell’s membrane through the extracellular matrix. ‘Irregular’ dystrophin = muscular dystrophy Post-AP DNA/Genetics – Mrs. Kelavkar More Complex Organisms • Humans have ~35,000 genes – Genes are located on chromosomes There is a fairly predictable flow to it all… Gene → Protein → Cell Processes → Organism It may be simple, but it illustrates 2 very powerful aspects of genetic analysis. Post-AP DNA/Genetics – Mrs. Kelavkar The 2 Important Aspects 1. We can study microscopic changes in DNA and these changes are revealed by phenotype 2. We can study the function of individual proteins by examining the consequences of eliminating that one protein function (‘knockout’ mice) These are 2 of the main themes studied in genetics! Some Terms You Should Know Alleles: Different versions of the same gene Mutation: An altered version of a gene Genotype: All of the alleles in an organism Phenotype: The physical result of the genotype Wild Type: It’s the standard (think of it like the control) Post-AP DNA/Genetic – Mrs. Kelavkar Any Questions? Post-AP DNA/Genetics – Mrs. Kelavkar Wheeler High School The Center for Advanced Studies in Science, Math & Technology Model Organisms & Key Players Genetics Lecture 2 Post-AP DNA/Genetics – Mrs. Kelavkar Table 1-2 Copyright © 2006 Pearson Prentice Hall, Inc. Model Organisms Why do genetic studies rely on the use of model organisms? 1. 2. 3. 4. Short life cycle Easy to maintain in the lab (usually) Lots of offspring Fairly straightforward genomes & anatomy Post-AP DNA/Genetics – Mrs. Kelavkar Escherichia coli E. coli • Gram negative • Different serotypes – Different serotypes = different surface antigens • Named after Austrian doctor, Theodor von Escherich, who isolated it from the intestines of animals – – – – Isolated in 1922 First bacterium to have genome sequenced ~4.6 million bases Important because it has many genes that are found in common organisms Post-AP DNA/Genetics – Mrs. Kelavkar Escherichia coli E. coli •Studied by many early geneticists –Most famous is Avery, MacLeod & McCarty’s 1944 experiment illustrating transformation • Remember that “transformation” was first described by Griffith in 1928 –Experiment showed DNA was genetic material Post-AP DNA/Genetics – Mrs. Kelavkar T Phage infecting E. coli Viruses that infect bacteria are called bacteriophages (geeky geneticists call them ‘phages’ for short). Seymour Benzer genetically mapped >2400 mutations in the T4 rII gene. Figure 1-7 Copyright © 2006 Pearson Prentice Hall, Inc. Saccharomyces cerevisiae Yeast Why do geneticists love yeast? 1. Non pathogenic eukaryote 2. Grows rapidly on glucose 3. Easy transformation 4. ~6,000 genes, all sequenced Drosophila melanogaster Fruit fly •Used to study humanspecific diseases •3 pairs of autosomes and an X and Y •Life cycle & mating behavior very well understood –Morgan & Benzer –Many mutants identified –Almost ALL genes have human orthologs Figure 1-6 Copyright © 2006 Pearson Prentice Hall, Inc. Drosophila melanogaster Fruit fly Thomas Hunt Morgan & his “Raiders” • Discovered the following (and many more): – – – – White-eye mutation Sex-linkage & segregation Nondisjunction & crossing-over The “clock” gene • Benzer worked on this too. He was convinced that our circadian rhythms had a genetic basis. – “Notch” gene • Led to discovery of Huntington’s mutation Post-AP DNA/Genetics – Mrs. Kelavkar Caenorhabditis elegans C. elegans • • • • • Soil dwelling nematode ~1 mm Sydney Brenner (1974) Has nervous system First multicellular organism to have it’s genome sequenced • Many conserved protein sequences & human orthologs – Shows quick evolutionary patterns Post-AP DNA/Genetics – Mrs. Kelavkar Danio rerio Zebrafish Mutation in the pigment gene (1 bp difference in humans). • Vertebrate, Freshwater • Used to study embryonic development and development of vertebrates – Large, transparent eggs • Mutations in the two cell singaling genes, PSEN1 and PSEN2, are studied in zebrafish – Mutations in these genes can lead to Alzheimers disease Post-AP DNA/Genetics – Mrs. Kelavkar Mus musculus The common mouse • Mammals and therefore share a high degree of homology with humans • ~3 billion bp’s • Knockout mice – gene is ‘knocked out’; used to study function of genes • Oncomice – activated oncogene mutant; lead to cancer • Transgenic mice – foreign genes inserted in to their genome Post-AP DNA/Genetics – Mrs. Kelavkar What causes obesity? Genetics, environment, combo of both? Post-AP DNA/Genetics – Mrs. Kelavkar Some Terms You Should Know • Homologue: A gene related to a second gene by descent from a common ancestral DNA sequence. There are 2 main types of homologues… – Ortholog: genes in different species that evolved from a common ancestral gene by speciation (normally, orthologs retain the same function in the course of evolution) • Always the result of speciation – Paralogs: genes related by duplication within a genome • Orthologs retain the same function in the course of evolution, whereas paralogs evolve new functions Post-AP DNA/Genetics – Mrs. Kelavkar Any Questions? Yes…we will study C. elegans and you will need to understand their mating patterns. Post-AP DNA/Genetics – Mrs. Kelavkar 1.1 From Mendel to DNA in Less Than a Century 1.1.2 The Chromosome Theory of Inheritance: Uniting Mendel and Meiosis Figure 1-2 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 1-3 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 1-5 Copyright © 2006 Pearson Prentice Hall, Inc. 1.1 From Mendel to DNA in Less Than a Century 1.1.3 Genetic Variation Mendel 1857 1.1 From Mendel to DNA in Less Than a Century 1.1.4 The Search for the Chemical Nature of Genes: DNA or Protein? Fredrick Griffith 1928 Non-virulent bacteria transformed to virulent strain Thomas Morgan 1933 Chromosome as heredity material 1.2 Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.1 The Structure of DNA and RNA Rosalind Franklin 1953-56 Maurice Wilkins and Watson & Crick 1953-58 Figure 1-8 Copyright © 2006 Pearson Prentice Hall, Inc. 1.2 Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.2 Gene Expression: From DNA to Phenotype Edwin Chargaff 1940’s AT & GC Complimentary rule Figure 1-9 Copyright © 2006 Pearson Prentice Hall, Inc. 1.2 Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.3 Proteins and Biological Function Messelson and Stahl Semiconservative mode of replication 1958-59 Figure 1-10 Copyright © 2006 Pearson Prentice Hall, Inc. 1.2 Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.4 Linking Genotype to Phenotype: Sickle-Cell Anemia Figure 1-11 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 1-12 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 1-13 Copyright © 2006 Pearson Prentice Hall, Inc. 1.3 Genomics Grew Out of Recombinant DNA Technology 1.3.1 Making Recombinant DNA Molecules and Cloning DN Figure 1-14 Copyright © 2006 Pearson Prentice Hall, Inc. 1.3 Genomics Grew Out of Recombinant DNA Technology 1.3.2 Sequencing Genomes: The Human Genome Project 1992-93 Beginning 2002-2003 Completed Craig Venter Celera Genomics & J. Craig Venter Institute Francis Collins Physician - geneticist Director of National Institutes of Health Figure 1-15 Copyright © 2006 Pearson Prentice Hall, Inc. 1.4 The Impact of Biotechnology Is Growing 1.4.1 Plants, Animals, and the Food Supply Table 1-1 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 1-16 Copyright © 2006 Pearson Prentice Hall, Inc. 1.4 The Impact of Biotechnology Is Growing 1.4.2 Who Owns Transgenic Organisms? Figure 1-18 Copyright © 2006 Pearson Prentice Hall, Inc. 1.5 Genetic Studies Rely On the Use of Model Organisms Why? What are the advantages to researchers? 1.5 Genetic Studies Rely On the Use of Model Organisms 1.5.1 The Modern Set of Genetic Model Organisms 1.5 Genetic Studies Rely On the Use of Model Organisms 1.5.2 Model Organisms and Human Diseases Zoonotic Diseases Animals to Humans transmission & visa versa