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Big Idea 3- Part C Gene Regulation Regulation of metabolic pathways Bacterial control of gene expression Operon: cluster of related genes with on/off switch Three Parts: 1. Promoter – where RNA polymerase attaches 2. Operator – “on/off”, controls access of RNA poly 3. Genes – code for related enzymes in a pathway Regulatory gene: produces repressor protein that binds to operator to block RNA poly Repressible Operon (ON OFF) Repressible Operon Normally ON Anabolic (build organic molecules) Organic molecule product acts as corepressor binds to repressor to activate it Operon is turned OFF Eg. trp operon trp operon Inducible Operon Normally OFF Catabolic (break down food for energy) Repressor is active inducer binds to and inactivates repressor Operon is turned ON Eg. lac operon lac operon • Typical human cell: only 20% of genes expressed at any given time • Different cell types (with identical genomes) turn on different genes to carry out specific functions • Differences between cell types is due to differential gene expression Eukaryotic gene expression regulated at different stages Chromatin Structure: • Tightly bound DNA less accessible for transcription • DNA methylation: methyl groups added to DNA; tightly packed; transcription • Histone acetylation: acetyl groups added to histones; loosened; transcription Transcription Initiation: • Control elements bind transcription factors • Enhances gene expression Transcription Initiation Complex Enhancer regions bound to promoter region by activators Regulation of mRNA: • micro RNAs (miRNAs) and small interfering RNAs (siRNAs) can bind to mRNA and degrade it or block translation Embryonic Development: Zygote Organism 1. Cell Division: large # identical cells through mitosis 2. Cell Differentiation: cells become specialized in structure & function 3. Morphogenesis: “creation of form” – organism’s shape Determination: irreversible series of events that lead to cell differentiation • Cytoplasmic determinants: maternal substances in egg distributed unevenly in early cells of embryo • Induction: cells triggered to differentiate • Cell-Cell Signals: molecules produced by one cell influences neighboring cells – Eg. Growth factors Pattern formation: setting up the body plan (head, tail, L/R, back, front) Morphogens: substances that establish an embryo’s axes Homeotic genes: master control genes that control pattern formation (eg. Hox genes) Control of Cell Cycle: 1. Proto-oncogene = stimulates cell division 2. Tumor-suppressor gene = inhibits cell division • Mutations in these genes can lead to cancer Proto-oncogene Oncogene Genes involved in cancer: • Ras gene: stimulates cell cycle (proto-oncogene) • Mutations of ras occurs in 30% of cancers • p53 gene: tumor-suppresor gene • Functions: halt cell cycle for DNA repair, turn on DNA repair, activate apoptosis (cell death) • Mutations of p53 in 50+% of cancers • Cancer results when mutations accumulate (5-7 changes in DNA) • Active oncogenes + loss of tumor-suppressor genes • The longer we live, the more likely that cancer might develop Bacteria vs.Viruses Bacteria • Prokaryotic cell • Most are free-living (some parasitic) • Relatively large size • Antibiotics used to kill bacteria Virus • Not a living cell (genes packaged in protein shell) • Intracellular parasite • 1/1000 size of bacteria • Vaccines used to prevent viral infection • Antiviral treatment Viruses • Very small (<ribosomes) • Components = nucleic acid + capsid – Nucleic acid: DNA or RNA (double or singlestranded) – Capsid: protein shell – Some viruses also have viral envelopes that surround capsid • Limited host range (eg. human cold virus infects upper respiratory tract) • Reproduce within host cells Simplified viral replicative cycle Bacteriophage • Virus that infects bacterial cells Lytic Cycle of T4 Phage Bacteriophage Reproduction • Lytic Cycle: – Use host machinery to make copies of virus – Death of host cell by rupturing it (lysis) – Virulent phages replicate by this method • Lysogenic Cycle: – Phage DNA incorporated into host DNA and replicated along with it – Phage DNA = prophage • Temperate Phage: uses both methods of replication Lytic Cycle vs. Lysogenic Cycle Animal viruses have a membranous envelope • Host membrane forms around exiting virus • Difficult for host immune system to detect virus Retrovirus • RNA virus that uses reverse transcriptase (RNA DNA) • Newly made viral DNA inserted into chromosome of host • Host transcribes viral DNA (= provirus) to make new virus parts • Example: HIV (Human Immunodeficiency Virus) HIV = Retrovirus HIV ◦ Infects white blood cells ◦ HIV+: provirus (DNA inserted) ◦ AIDS: active viral reproduction Vaccines • Weakened virus or part of pathogen that triggers immune system response Emerging viruses = mutation of existing viruses Viroids • Small, circular RNA molecules that infect plants • Cause errors in regulatory systems that control plant growth • Eg. coconut palms in Philippines Prions • Misfolded, infectious proteins that cause misfolding of normal proteins • Eg. mad cow disease (BSE),Creutzfeldt-Jakob disease (humans), scrapie (sheep) Diseases caused by prions • Prions act slowly – incubation period of at least 10 years before symptoms develop • Prions are virtually indestructible (cannot be denatured by heating) • No known cure for prion diseases