AP Biology, Chapter 18
Microbial Models: The Genetics of Viruses and Bacteria

Summary
Introduction

THE GENETICS OF VIRUSES
	Researchers discovered viruses by studying a plant disease: science as a process
		1. Recount the history leading up to the discovery of viruses. Include the contributions of 
		Adolf Mayer, D. Ivanowsky, Martinus Beijerinck, and Wendell Stanley.
			a. Mayer, tobacco mosaic disease
				i. Symptoms: stunted growth, mottled leaf color
				ii. Transmitted experimentally by spraying extract of diseased plants
				iii. Agent could not be grown in a Petri dish
			b. D. Ivanowsky
				i. Agent could pass through porcelain filters that trapped all known 
				bacteria
				ii. Thought it was a new smaller bacteria or a toxin
			c. Beijerinck
				i. Showed agent could reproduce by serial passage
				ii. Showed agent was not killed by alcohol  not cellular
			d. Stanley: purified and crystallized the tobacco mosaic virus  
	A virus is a genome enclosed in a protective coat
		2. List and describe the structural components of viruses.
			a. Genome
				i. DNA or RNA
				ii. Single-stranded or double-stranded
				iii. Four to hundreds of genes
			b. Capsid
				i. Composed of capsomere protein subunits
				ii. Protects genome, enables infection
			c. Envelope
				i. Lipid and protein bilayer surrounding capsid
	Viruses can reproduce only within a host cell: an overview
		3. Explain why viruses are obligate parasites.
			a. Physical requirements for life
				i. Translational components
				ii. ATP production apparatus
				iii. Active boundary
			b. Viruses have none
	Phages reproduce using lytic or lysogenic cycles
		4. Distinguish between the lytic and lysogenic reproductive cycles, using phage T4 and 
		phage lambda as examples.
			a. Lytic: continuously active infection (T4)
				i. Tail fibers attach to specific receptors on host
				ii. Tail contracts to inject DNA chromosome
				iii. T4 exonucleases chop up host's DNA
				iv. Host transcription and translation apparatus expresses viral genome
				v. Viral and host DNA polymerases copy T4 genome
				v. Self-assemble by matching shapes with help from assembly factors
				vi. Viral lysozyme digests bacteria from the inside out
			b. Lysogenic: includes a phase of dormancy (λ)
				i. Attachment and injection
				ii. Genome circularizes, recombines into host cell chromosome
				iii. Now called a prophage, replicated along with host chromosome
				iv. Phage repressor gene is expressed, maintains dormancy
				v. Environmental triggers can overcome repression
				vi. Prophage cuts itself out, enters lytic cycle
			c. Bacterial host defenses
				i. Mutations of receptor on cell surface
				ii. Restriction endonucleases cut viral DNA upon injection
	Animal viruses are diverse in their modes of infection and replication
		5. Describe the reproductive cycle of an enveloped virus. Explain how the reproductive 
		cycle of herpes viruses is different.
			a. Most enveloped viruses (HIV, influenza)
				i. Glycoproteins on envelope fuse with receptors on host membrane
				ii. Capsid removed by host cell enzymes
				iii. Viral genome expressed and replicated
				iv. ER makes viral envelope with glycoproteins  plasma membrane
				v. Capsid assembles with copies of genome
				vi. Attach to inside of PM with envelope glycoproteins and bud out				b. Herpesviruses 
				i. May integrate into host chromosome = provirus
				ii. Can remain dormant like prophage
				iii. Bud through the nuclear membrane instead of plasma membrane
		6. Describe the reproductive cycle of retroviruses.
			a. Single-stranded RNA viruses
			b. RNA genome copied into DNA by reverse transcriptase
			c. Double-stranded DNA form integrated as a provirus
			d. Host RNA polymerase makes viral mRNA and genome
			e. Enveloped through the PM 
		7. Explain how viral infections in animals cause disease.
			a. Mechanisms of cell damage or killing
				i. Release lysosomal enzymes
				ii. Make host cells produce toxins
				iii. Viral proteins may be toxins
			b. Depending on tissue attacked damage may temporary and brief
		8. Define "vaccine" and describe the research of Jenner that led to the development of 
		the smallpox vaccine.
			a. Harmless variants or derivatives of pathogens formulated to stimulate 
			immunity
			b. Jenner, late 1700s
				i. Milkmaids recovered from cowpox were immune to smallpox
				ii. Used fluid from a cowpox sore as a vaccine
		9. Describe the best current medical defenses against viruses. Explain how AZT helps to 
		fight HIV infections.
			a. Medical defenses
				i. Vaccination
				ii. Agents that bind to the receptor or its ligand
				iii. Entry-blockers for influenza, hepatitis B and C
				iv. Nucleotide or nucleoside analogs like acyclovir for herpes
				v. Protease inhibitors in use for HIV
			b. AZT
				i. Nucleoside analog for thymidine
				ii. Inhibits reverse transcriptase

		10. Describe the mechanisms by which new viral diseases emerge.
			a. Mutation of existing viruses
			b. Transmission from one species to another
			c. Spreading out from an isolated population
		11. List some viruses that have been implicated in human cancers and explain how tumor 
		viruses transform cells.
			a. Human cancer viruses
				i. Hepatitis B: liver cancer
				ii. Epstein-Barr: Burkitt's lymphoma
				iii. May Human papilloma virus: cervical cancer
				iv. HTLV-1: adult leukemia
			b. Oncogenes
				i. Viral genes that can trigger cancer
				ii. Host homologues are proto-oncogenes
				iii. All are involved in cell cycle control
				iv. in addition, may require an environmental agent
	Plant viruses are serious agricultural pests
		12. Distinguish between the horizontal and vertical routes of viral transmission in plants.
			a. Horizontal: transfer from another infected plants by insects, equipment
			b. Vertical: from a parent through the seed or by asexual reproduction
	Viroids and prions are infectious agents even simpler than viruses
		13. Describe the structures and replication cycles of viroids and prions.
			a. Viroids
				i. Small rings of non-encapsulated RNA with no protein-coding regions
				ii. Use host cell RNA polymerase to reproduce
				iii. Disrupt metabolism, cause abnormal development and stunted growth
				iv. Transmitted by insects or mechanically
			b. Prions
				i. Infectious protein causing kuru, Creutzfeldt-Jacob, mad cow, chronic 
				wasting diseases (spongiform encephalopathies)
				ii. Abnormally shaped protein bends normal to abnormal
				iii. Also a genetic form, familial fatal insomnia, missense mutation of the 
				prion gene, autosomal dominant  
				iv. Transmitted by feeding
	Viruses may have evolved from other mobile genetic elements
		14. List some characteristics that viruses share with living organisms and explain why 
		viruses do not fit our usual definition of life.
			a. Code-carrying, separate, reproduce, mutate, evolve
			b. Viruses lack these physical requirements for life
				i. Translational components
				ii. ATP production apparatus
				iii. Active boundary
		15. Describe the evidence that viruses probably evolved from fragments of cellular 
		nucleic acid.
			a. Sequence resembles host more than other viruses
			b. Resemble known mobile genetic elements
				i. Plasmids
					. Small circular DNAs
					. In nature have genes promoting their transfer
					. Now artificially simplified for lab use
				ii. Transposons
					. DNA segments that can copy themselves and move in a 
					Genome
					. Identified in all species, cause mutations as they move
			c. Could be degenerate, formerly cellular, intracellular parasites

THE GENETICS OF BACTERIA
	The short generation span of bacteria facilitates their evolutionary adaptation to 
	changing environments
		16. Describe the structure of a bacterial chromosome.
			a. Circular
			b. E. coli has about 4300 genes
		17. Describe the process of binary fission in bacteria.
			a. Chromosome copied
				i. Single origin of replication
				ii. Mutation rate = 10-7/gene/replication
				iii. Copies attached to cell membrane/ cell wall
			b. As cell and cell wall grows, copies are dragged apart
		18. Compare the sources of genetic variation in bacteria and humans.
			a. Bacteria: rapid growth in large populations allows mutation to provide diversity
			b. Human: most variation from sexual recombination of existing alleles
	Genetic recombination produces new bacterial strains
		19. Compare the processes of transformation, transduction, and conjugation.
			a. Transformation
				i. Uptake of uncoated DNA by cells
				ii. Genetic recombination adds it to the genome
				iii. Some species have DNA receptors for uptake
				iv. Others will take up DNA after treatment with Ca ions
			b. Transduction
				i. Phages can carry DNA from one host cell to another
				ii. Generalized: pieces of host cell DNA are accidentally packaged
				iii. Specialized: excision of a prophage may include neighboring bacterial 
				DNA
			c. Conjugation
				i. Large 25-gene plasmids have genes useful for their transfer
				ii. In conjugation, bacterial cells temporarily fuse
					. Those carrying the fertility factor (F plasmid) are termed male
					. The F factor is copied and the copy is transferred to the 
					recipient
		20. Distinguish between plasmids and viruses. Define an episome.
			a. Plasmids lack capsids and don't exist outside the cell
			b. Plasmids and phages may replicate separate from, or recombined into, the 
			host chromosome
		21. Explain how the F plasmid controls conjugation in bacteria.
			a. Genes on F plasmid produce sex pili extending from the cell
			b. Sex pilus attaches to cells lacking the F plasmid, promoting fusion
			c. F plasmid is an episome
				i. When separate from bacterial chromosome it transfers itself
				ii. When attached, transfer continues around the bacterial chromosome 
				= high frequency of recombination (Hfr)
		22. Describe the significance of R plasmids. Explain how the widespread use of 
		antibiotics contributes to R-plasmid-related disease.
			a. R = resistance; R-plasmids carry antibiotic resistance genes
			b. For example, a gene for penicillinase
			c. In populations
				i. Treatment with antibiotic kills all the sensitive bacteria
				ii. Resistant strains are the only ones left to reproduce
		23. Define transposon and describe two types of transposition.
			a. = transposable genetic element; can move around the genome
			b. Types of transposition
				i. Cut-and-paste; remove at one location, add at another
				ii. Replicative; make a copy, inserted at a new location
			c. Also found in eukaryotes; McClintock, corn, 1950s
		24. Distinguish between an insertion sequence and a complex transposon.
			a. Insertion sequences
				i. Only have DNA for transposition
				ii. Has transposase gene between inverted repeats
				iii. Can cause mutation at insertion sites
			b. Composite transposons
				i. Extra genes between two complete insertion sequences
				ii. Extra genes may be for antibiotic resistance
		25. Describe the role of transposase and DNA polymerase in the process of transposition.
			a. Transposase
				i. Binds to inverted repeats
				ii. Cuts and reseals DNA
			b. DNA polymerase adds direct repeats at the ends of the inverted repeats
	The control of gene expression enables individual bacteria to adjust their metabolism 
	to environmental change
		26. Briefly describe two main strategies that cells use to control metabolism.
			a. Regulate enzyme activity
				i. End product of the pathway feedback to stop its production
				ii. Binds to 1st enzyme in the pathway; non-competitive or allosteric
			b. Regulate gene expression
				i. Turn genes on and off by controlling the initiation of transcription
				ii. Takes longer
		27. Explain the adaptive advantage of genes grouped into an operon.
			a. Operon = operator, promoter, and the genes they control
			b. Puts functionally related genes under the control of a single on-off switch
		28. Using the trp operon as an example, explain the concept of an operon and the 
		function of the operator, repressor, and co-repressor.
			a. Separate repressor gene is expressed constitutively
			b. Corepressor = tryptophan
			c. Repressor + tryptophan binds to operator and blocks transcription
			d. When tryptophan is low, repressor alone releases from operator
		29. Distinguish between structural and regulatory genes.
			a. Structural genes code of enzymes in a biosynthetic pathway
			b. Regulatory genes code for proteins that turn operons on or off
		30. Describe how the lac operon functions and explain the role of the inducer, 
		allolactose.
			a. Separate repressor gene is expressed constitutively
			b. Repressor alone binds to operator, blocks transcription
			c. Inducer allolactose binds to repressor and it releases from the operator
			d. RNA polymerase can the transcribe the genes required for lactose digestion
		31. Explain how repressible and inducible enzymes differ and how those differences 
		reflect differences in the pathways they control.
			a. Respressible
				i. Small molecule binds respressor and turns off the operon
				ii. Useful for anabolic pathways; enough product turns off pathway
			b. Inducible
				i. Small molecule binds repressor and turns on the operon
				ii. Useful for catabolic pathways; presence turns on genes to digest
		32. Distinguish between positive and negative control and give examples of each from 
		the lac operon.
			a. Negative
				i. Operon switched off by active repressor
				ii. Lac repressor without allolactose binds to operator, blocks 
				transcription
			b. Positive
				i. Operon switched on by active regulatory protein
				ii. CRP protein + cAMP binds to DNA, helps RNA polymerase bind to 
				promoter
		33. Explain how cyclic AMP and the cyclic AMP receptor protein are affected by glucose 
		concentration.
			a. Glucose plentiful
				i. cAMP is not made in the cytoplasm
				ii. CRP doesn't bind to DNA, RNA polymerase doesn't bind as much
			b. Glucose low
				i. cAMP made
				ii. cAMP + CRP bind and increase transcription