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Chapter 18 Viral and Bacterial Genetics AP Biology Hepatitis Viral diseases Polio Measles AP Biology Chicken pox 2005-2006 Influenza: 1918 epidemic 30-40 million deaths world-wide RNA virus AP Biology 2005-2006 Smallpox Eradicated in 1976 vaccinations ceased in 1980 at risk population? AP Biology 2005-2006 Emerging viruses Viruses that “jump” host switch species Ebola, SARS, bird flu, hantavirus AP Biology Ebola SARS hantavirus A sense of size Comparing size eukaryotic cell bacterium virus AP Biology 2005-2006 What is a virus? Is it alive? DNA or RNA enclosed in a protein coat Viruses are not cells Extremely tiny electron microscope size smaller than ribosomes ~20–50 nm 1st discovered in plants (1800s) tobacco mosaic virus couldn’t filter out couldn’t reproduce on media AP Biology like bacteria 2005-2006 Variation in viruses Parasites AP Biology plant virus pink eye lack enzymes for metabolism lack ribosomes for protein synthesis need host “machinery” 2005-2006 Variation in viruses A package of influenza bacteriophage genes in transit from one host cell to another “A piece of bad news wrapped in protein” – Peter Medawar AP Biology 2005-2006 Viral genomes Viral nucleic acids DNA double-stranded single-stranded RNA double-stranded single-stranded Linear or circular smallest viruses have only 4 genes, while largest have several hundred AP Biology 2005-2006 Viral protein coat Capsid crystal-like protein shell 1-2 types of proteins many copies of same protein AP Biology 2005-2006 Viral envelope Lipid bilayer membranes cloaking viral capsid envelopes are derived from host cell membrane glycoproteins on surface AP Biology HIV 2005-2006 Generalized viral lifecycle Entry virus DNA/RNA enters host cell Assimilation viral DNA/RNA takes over host reprograms host cell to copy viral nucleic acid & build viral proteins Self assembly nucleic acid molecules & capsomeres then selfassemble into viral particles exit cell AP Biology 2005-2006 Symptoms of viral infection Link between infection & symptoms varies kills cells by lysis cause infected cell to produce toxins fever, aches, bleeding… viral components may be toxic envelope proteins Damage? depends… lung epithelium after the flu is repaired nerve cell damage from polio is permanent AP Biology Viral hosts Host range most types of virus can infect & parasitize only a limited range of host cells identify host cells via “lock & key” fit between proteins on viral coat & receptors on host cell surface broad host range rabies = can infect all mammals narrow host range human cold virus = only cells lining upper respiratory tract of humans HIV = binds only to specific white blood cells AP Biology Bacteriophages Viruses that infect bacteria ex. phages that infect E. coli lambda phage 20-sided capsid head encloses DNA protein tail attaches phage to host & injects phage DNA inside AP Biology 2005-2006 Bacteriophage lifecycles Lytic reproduce virus in bacteria release virus by rupturing bacterial host Lysogenic integrate viral DNA into bacterial DNA reproduce with bacteria AP Biology Lytic lifecycle of phages AP Biology 2005-2006 Lysogenic lifecycle of phages AP Biology 2005-2006 Defense against viruses Bacteria have defenses against phages bacterial mutants with receptors that are no longer recognized by a phage natural selection favors these mutants bacteria produce restriction enzymes recognize & cut up foreign DNA It’s an escalating war! AP Biology natural selection favors phage mutants resistant to bacterial defenses When do we need to cut DNA? This will be important! RNA viruses Retroviruses have to copy viral RNA into host DNA enzyme = reverse transcriptase RNA DNA mRNA host’s RNA polymerase now transcribes viral DNA into viral mRNA mRNA codes for viral components host’s ribosomes produce new viral proteins transcription DNA replication AP Biology RNA translation protein Why is this significant? Retroviruses HIV Human ImmunoDeficiency Virus causes AIDS Acquired ImmunoDeficiency Syndrome opportunistic diseases AP Biology envelope with glycoproteins for binding to specific WBC capsid containing 2 RNA strands & 2 copies of reverse transcriptase 2005-2006 HIV infection HIV enters host cell macrophage & CD4 WBCs cell-surface receptor reverse transcriptase synthesizes double stranded DNA from viral RNA high mutation rate Transcription produces more copies of viral RNA AP Biology translated into viral proteins proteins & vRNA self-assemble into virus particles released from cell by “budding” or by lysis 2005-2006 HIV treatments inhibit vRNA replication AZT thymine mimic protease inhibitors AP Biology stops cleavage of polyprotein into capsid & enzyme proteins 2005-2006 Potential HIV treatments Block receptors chemokines bind to & block cell-surface receptors 11% of Caucasians have mutant receptor allele Block vRNA replication AP Biology CAF replication factor 2005-2006 Cancer viruses Viruses appear to cause certain human cancers hepatitis B virus linked to liver cancer Epstein-Barr virus = infectious mono linked to lymphoma papilloma viruses linked with cervical cancers HTLV-1 retrovirus linked to adult leukemia AP Biology Cancer viruses Transform cells into cancer cells after integration of viral DNA into host DNA carry oncogenes that trigger cancerous characteristics in cells version of human gene that normally controls cell cycle or cell growth Most tumor viruses probably cause cancer only in combination with other mutagenic events AP Biology Prions Misfolded proteins infectious make plaques (clumps) & holes in brain as neurons die Creutzfeldt-Jakob disease “mad cow” disease AP Biology 2005-2006 1982 | 1997 Protein as information molecule?! Prions challenge Central Dogma transmit information to other proteins Pn Pd Stanley Prusiner UC School of Medicine AP Biology proteinaceous infectious 2005-2006 molecule Ch. 18: Control of Prokaryotic (Bacterial) Genes AP Biology 2007-2008 Prokaryotic Gene Control Bacteria need to respond quickly to changes in their environment Transcription and translation happen simultaneously…they are “coupled!” Transcription is what is regulated. Lack of nucleus makes this very efficient! AP Biology Bacterial metabolism Bacteria need to respond quickly to changes in their environment if they have enough of a product, need to stop production why? waste of energy to produce more STOP GO AP Biology how? stop production of enzymes for synthesis if they find new food/energy source, need to utilize it quickly why? metabolism, growth, reproduction how? start production of enzymes for digestion Remember Regulating Metabolism? Feedback inhibition - = inhibition product acts as an allosteric inhibitor of 1st enzyme in tryptophan pathway but this is wasteful production of enzymes Oh, I remember this from our Metabolism Unit! AP Biology - Different way to Regulate Metabolism Gene regulation - = inhibition instead of blocking enzyme function, block transcription of genes for all enzymes in tryptophan pathway saves energy by not wasting it on unnecessary protein synthesis AP Biology Now, that’s a good idea from a lowly bacterium! - - Gene regulation in bacteria Cells vary amount of specific enzymes by regulating gene transcription turn genes on or turn genes off turn genes OFF example if bacterium has enough tryptophan then it STOP doesn’t need to make enzymes used to build tryptophan turn genes ON example if bacterium encounters new sugar (energy GO source), like lactose, then it needs to start making enzymes used to digest lactose AP Biology Bacteria group genes together Operon genes grouped together with related functions example: all enzymes in a metabolic pathway Two types: INDUCIBLE and REPRESSIBLE promoter = RNA polymerase binding site single promoter controls transcription of all genes in operon transcribed as one unit & a single mRNA is made AP Biology operator = DNA binding site of repressor protein Operon model Operon: operator, promoter & genes they control serve as a model for gene regulation RNA polymerase RNA repressor polymerase gene1 gene2 gene3 gene4 1 2 3 4 enzyme1 enzyme2 enzyme3 enzyme4 mRNA promoter DNA operator Repressor protein turns off gene by blocking AP BiologyRNA polymerase binding site. repressor = repressor protein Repressible operon: tryptophan Synthesis pathway model When excess tryptophan is present, it binds to tryp repressor protein & triggers repressor to bind to DNA RNA polymerase RNA trp repressor polymerase gene1 gene2 gene3 gene4 1 2 3 4 enzyme1 enzyme2 enzyme3 enzyme4 mRNA promoter blocks (represses) transcription DNA trp operator trp trp repressor repressor protein trp trp trp trp trp trp conformational change in AP Biologyprotein! repressor trp repressor tryptophan trp tryptophan – repressor protein complex Tryptophan operon What happens when tryptophan is present? Don’t need to make tryptophan-building enzymes Tryptophan AP Biology is allosteric regulator of repressor protein Inducible operon: lactose lac lac RNA polymerase lac Digestive pathway model lac When lactose is present, binds to lac repressor protein & triggers repressor to release DNA lac lac lac RNA lac repressor TATA polymerase induces transcription gene1 gene2 gene3 gene4 1 2 3 4 enzyme1 enzyme2 enzyme3 enzyme4 mRNA promoter operator repressor lac conformational change in AP Biologyprotein! repressor lac repressor DNA repressor protein lactose lactose – repressor protein complex Lactose operon What happens when lactose is present? Need to make lactose-digesting enzymes Lactose is allosteric regulator of repressor protein AP Biology So how can these genes be turned off? Repressor protein binds to DNA at operator site blocking RNA polymerase blocks transcription AP Biology UpRegulation – increase the rate! Ex: CAP/cAMP system When lactose is present and glucose is low: cAMP is high cAMP activates Catabolite Activator Protein (CAP) Increases the rate of transcription by 100x! AP Biology 1961 | 1965 Jacob & Monod: lac Operon Francois Jacob & Jacques Monod first to describe operon system coined the phrase “operon” AP Biology Jacques Monod Francois Jacob Operon summary Repressible operon usually functions in anabolic pathways synthesizing end products when end product is present in excess, cell allocates resources to other uses Inducible operon usually functions in catabolic pathways, digesting nutrients to simpler molecules produce enzymes only when nutrient is available cell avoids making proteins that have nothing to do, AP Biology cell allocates resources to other uses Don’t be repressed! How can I induce you to ask Questions? AP Biology