3. You can go into Gradescope and use the regrade request to explain to me for each question you originally got wrong and would like points for: "Before I thought ___________, now I think ___________"
4. Your answer must make clear to me what thinking led you to get a wrong answer, and make clear that you now understand how to get the right answer!
Learning objectives
Outline the different ways that gene mutations may arise
Explain how mutations have been detected and studied
Describe the features and effects of transposable elements
Types & effects of mutations
Causes of mutations
Studying mutations
Types & effects of transposons
Gene mutations
Nucleotide tautomers
Nonstandard base pairing
Strand slippage (insertions/deletions)
Unequal crossing over
Depurination
Deamination
Tautomers
Molecules may take on more than one arrangement of atoms
Tautomers
May cause base substitutions
Tautomers
Usually cause A::T -> A::C transitions (pyrimidine -> pyrimidine)
Depurination
Purines are vulnerable to spontaneous loss
Deamination
Removal of the amine group from cytosine converts it into uracil
Causes of spontaneous mutations
Nucleotide tautomers
Nonstandard base pairing
Strand slippage
Unequal crossing over
Depurination
Deamination
Induced mutations
Base analogs
DNA modifying agents
Intercalating agents
Base analogs
Structurally similar to normal bases, mistakes occur when incorporated into growing polynucleotide chain
DNA modifying agents
Alter a base causing it to mispair
Intercalating agents
Distort DNA to induce single nucleotide pair insertions and deletions
Mutagen effects
Increase normal mutation frequency
Cause point mutations
Cause frameshift mutations
Cause translocations and rearrangements
Types of chromosome mutations
Chromosome rearrangement
Aneuploidy
Polyploidy
Mutation rate
Frequency with which a wild type sequence at a locus changes into a mutant allele
Factors affecting measurable mutation rate
Frequency of changes in DNA
Probability of repair of an alteration in DNA
Probability of detection
Mutation rate is usually expressed as # of mutations / biological unit
Ames test
1. Bacterial strain with a mutation in a histidine synthesis gene
2. Mammalian liver enzymes
3. Your suspected mutagen
Ames test
Tests whether something might be a mutagen - an environmental agent that significantly increases the rate of mutation above the spontaneous rate
Positive Ames test = chemical is a mutagen in bacteria
Negative Ames test does not mean a chemical is not a carcinogen
Forward genetics
Observe a (mutant) phenotype, then look for the mutation that causes it
Reverse genetics
Make a mutation in a gene of interest, and look to see what the phenotype is
About 45% of our DNA appears to be left-over transposon sequences
Transposons
Mobile DNA elements that can move around the genome
Barbara McClintock's findings on transposons in corn were not initially accepted, but she was awarded the Nobel Prize in 1983
Types of transposons
DNA transposons (class II) - Direct DNA transposition
Retrotransposons (class I) - DNA -> RNA -> DNA
Types of transposition
Replicative transposition (copy/paste)
Non-replicative transposition (cut/paste)
Transposon insertion
Can disrupt gene expression and cause mutation
Transposons
Can increase risk of chromosome rearrangements through creating repeat sequences
Hybrid dysgenesis
Sudden appearance of numerous mutations, chromosome mutations, and sterility in hybrid offspring between two populations
45% of the human genome is derived from transposable elements
Alu is the most common transposable element in humans with > 1 million related copies
Transposable elements have been domesticated and aided in the evolution of the placenta in mammals