Lecture 13 Flashcards
Why are phenotypic mutation rates often much higher than per bp mutation rates?
As evolution relies on the heritable variation provide by phenotypic mutations
Contrast germline and somatic mutations.
Germline mutations occur in the lineage of cells that create gametes whereas Somatic mutations occur in non-gametic cells and CANNOT be passed from one generation to the next ( can inherited by mitosis)
If a gene has a synonymous mutation, what is the expected effect on the resultant protein?
A synonymous mutation is a point mutation where a single nucleotide is substituted with another which results in a different codon that still codes for the original protein. NO CHANGE IN RESULTANT PROTEIN
If a gene has a missense mutation, will that always disrupt the function of that protein? Why or why
not?
No as sometimes the change in the amino acid can be advantageous but mostly bad.
Missense mutation: codon chanted and specifices a difernt amino acid
nonsense mutations: codon changed to a premature stop codon (usually null allele)
frameshift mutations: freading frame altered sunsequent amino acids alterad and usually results in premature stop codon
only indels of multipels of 3 will affect reading frame
You are researching mutants of a gene encoding a particular enzyme. Two of the mutants you are
characterizing are nonsense mutations. One has zero activity, and one has near wild type levels of
activity. In terms of N-terminal/C-terminal (Lecture 7) and 5’/3’, give a likely explanation for the
difference between these two mutant genes.
the gene with zero activty are due to nonsense mutations at the 5’ end as it is very early in the mrna sequence making the translation into a protein nonfunctional
the gene with high wildtype activity occurs near the 3’ end
For the same enzyme you also have two insertion mutants you are testing. One has a 4bp insertion
and another has a 6 bp insertion. Which is more likely to be functional and why?
The 6bp insertion is more likely to be function as it is a multiple of 3 and will not affect the reading frame
What is a cryptic splice site? Why can a mutation that generates a cryptic splice site yield a loss of
function?
cryptic sites is a non splice site that competes with he authentic splice site leading to splcing at the incorrect sequence and altering the protein
What is the main consequence of a polyadenylation mutation that disrupts the polyadenylation
signal sequence?
less protein is made from the mrna as the mutation causes the poly a tail sequence to not be recognized and therefore the mrna is not adenylated and protected from degradation
What is the difference between a transition and a transversion? Which is more common? Which is
more likely to yield an amino acid change in coding sequence and why?
transversion: purine to pyrimidine
Transition: pyrmidine to purine
transition is more likely to occur but less likely to cause AA changes
since transitons in the 3rd position code for the same AA.
What are the key differences among the three different types of reversion mutations? What is one
way that all three categories are similar?
reversion: restores wildtype phenotype in a mutant
1. true reversion or back mutation: revert the exact mutation
2. intragenic: mutation within the same gene but at a different site; compensate but not by directly changing the original mutation
3. second site mutation: produced mutation in a different gene that complements the mutation
What is genetic anticipation? Why does it occur? Explain forward and backward replication
slippage in your answer.
genetic anticipation: diseases getting worse as it passes on through generation because backward slippage results in the repeated seq getting duplicated wheares forward sliipage results in the repeated seq being deleted
more repeates= more severity
What is a tautomeric shift and how can it lead to a mutation. Highlight the role of DNA replication
is making the error permanent in your answer.
tuatomeric shifts are shifts in nitrogenous bases to its tautomer
which leads to non watson and crick base pairing .
In DNA replication the interconversion mutation is not recognized so when1616+16161 replication occurs the mutation is carried through out generation
Why can depurination result in mutations?
depurination is the breakage of the bond between the 1’ carbon and the nitrogenous base
this removes a purine but if the depurinated strand is used as a template the polymerase defaults to adding an A which will result in a permanent mutaiotn
Why are CpG dinucleotides hypermutable?
when c is methylated it is more likely to be deaminated
bp with g it is more likely to be methylated and therefore hypermutable
You discover a chemical that you suspect may be mutagenic. Describe how you would use the
Ames test to determine if this were true.
mutagens generate mutations via inducing DNA Damage
( mutagens cause many somatic mutation and can lead to cancer
Ames test: His + plated on minimal media
need chemical to be tested
s9 liver extract ( chemical itself may not be mutagenic but it breaks down products could be so liver extract could break down chemical)
add chemical to paper disc
