Lecture #20 – 10/22/01 – Dr. Wormington
When Bad Things Happen to Good DNA!
"Small Scale" Genetic Mutations
Lose H-bond donor
X
Lose H-bond
acceptor
Gain H-bond donor
Imino
Now pairs with A
Amino tautomer normally Pairs w/ G
Fig. 12.19 has an Error! Delete this extraneous bond!
Even mutations don't generate pentavalent Carbon atoms!
More Bad Things That Can Happen to Good DNA!
"Small Scale" Genetic Mutations
Vegens & Wine Aficionados Beware!
Bisulfite used as anti-oxidant in wine &
To prevent veggies from wilting in salad bars
Nearly as potent a mutagen as Nitrous Acid
Lose H bond donor
HSO3
Gain H bond
acceptor
Generated by Breakdown Of Nitrites
Consumed as Preservatives
In Smoked Meats, Hot dogs etc.
Now pairs with A
Proofreading or
Mismatch Repair
Eliminate Mutation
CG Base Pair Converted to TA Base Pair
Pairs w/ A
During Replication
Deaminated C
Mismatch not corrected
Cytosine is Not the Only Base Which Can be Mutated
Potent Mutagen
Used in Laboratory
To Generate Mutants
GC Base Pair Converted
to AT Base Pair
Carcinogens (Chemicals Which Cause Cancer) = Mutagens
React Directly w/ DNA
Must 1st Be Metabolized Before Reacting w/ DNA
Dry Cleaning
Cigarettes
Exotic Food
Spice
Moldy Peanuts
Change 1 amino acid to another
Phe to Leu is a
Conservative
Substitution
Introduces a Premature Stop Codon Generates a truncated
protein. ~30% of all
human genetic diseases
due to nonsense mutations
Extra nucleotide incorporated during replication
4 nucleotides deleted during replication
Frameshift mutations most
deleterious as resultant protein
is almost always nonfunctional
•Some Final Thoughts on "Small" Mutations
•Not Every Mutation Has an Effect
Mutations in 3rd Position of Degenerate Codons
Often Don't Change Amino Acid
Synonym Codons Encode Similar Amino Acids
Not Every Nucleotide Is Present Within a Coding Region (or even a Gene!)
•Can Mutations Map Outside of Coding Regions?
Mutations Within Transcription Promoters Can Affect Gene Expression
"Up" Mutations Increase Amount of mRNA/Protein Product
"Down" Mutations Decrease Amount of mRNA/Protein Product
•Is There Anything You Can Do To Avoid Mutations?
•Don't Eat, Drink, Breath
•Don't Go Outside or Work Inside
•Mutations Drive Evolution!
•Without Mutations We'd Still be Amoebae
•Now Onto "Large Scale" Mutations
"Large" Scale Chromosomal Mutations
DNA molecule broken
at 2 sites by ionizing
radiation & rejoins w/o
middle fragment
Gamete will lack C&D
Homologous chromosomes
break at 2 different sites
& reattach at wrong places
"Nonreciprocal recombination"
Gamete has duplicated C&D
Zygote will be functionally triploid for these 2 genes
DNA molecule broken
at 2 sites by ionizing
radiation & rejoins w/
middle fragment reversed
"Nonhomologous"
chromosomes recombine
common in many cancers
Viruses – Molecular Parasites
• Causal Agents of Numerous Human Diseases Spanning the Cold to Cancer
Incl. Hepatitis, Flu, Ebola, Smallpox, Measles, Herpes, HIV, Polio, West Nile
• Relatively Small Genomes (DNA or RNA) Amenable to Genetic Analyses
• Relatively Simple Bipartite Gene Expression Program
“Early” Genes Expressed Before Viral Genome Replication
“Late” Genes Expressed After Viral Genome Replication
• Utilize Host Cell Biosynthetic Processes During Infection
Provide Excellent Models to Study Basic Molecular & Cellular Events
• Typically Proliferate By 1 of 2 Life Cycles – Some Viruses Exhibit Both
“Lytic” or “Productive” Infection Lyses & Usually Kills Infected Cell
Cells supporting Lytic Cycle Termed “Permissive”
• “Lysogenic” or “Nonproductive” Infection
Results in Integration of Viral DNA Into Host Cell Genome “Provirus”
Infectious Viral Progeny Usually Not Generated
Cells supporting Lysogenic Cycle Termed “Nonpermissive”
• Viruses Can Be Inhibited by Anti-viral Therapies or Vaccines, but not Antibiotics!