Mutation Flashcards
(14 cards)
What are mutations?
Small scale DNA sequence mutations
1. Substitutions
2. Deletions
3. Insertions
Describe the fidelity of DNA polymerase
High fidelity: most DNA polymerase incorporate the correct nucleotide with very high accuracy
Proofreading: built in proofreading exonuclease which corrects mismatched bases and reduces the overall error rate
Mismatch repair: cells also have repair mechanisms that further reduce errors, bringing final mutation rate down
Source of mutations: occasional replication errors slip through.
Variability: specialised or damage tolerant polymerases often have high error rates
Describe replication errors and mutagen-induced changes
Replication errors: spontaneous mistakes during DNA synthesis
Mutagens: environmental agents (chemical, physical, biological) that directly damage DNA or interfere with replication, causing elevated mutation rates
Describe the different point mutations
Silent (no change in protein), missense (amino acid change), nonsense (premature stop)
Transitions (purine to purine), transversions (purine to pyrimidine)
Describe tautomeric shifts as hidden error sources
Each base can briefly shift to a rare tautomeric form, pairing incorrectly during replication
Misparing despite “correct” nucleotide. Even though polymerase selects the right base, a momentary tautomeric shift can lead to a mismatch that remains once the base reverts to its common form
Chemical and physical causes?
Chemical causes: exposure to mutagens like alkylating agents, base anlogs or oxidative stress
Physical agents: radiation can physically damage DNA (e.g UV causes thymine dimers)
Describe the mutagenic effect of 5-bromouracil
Base analog action: 5-bromouracil mimics thymine but can pair with guanine, leading to transition mutations during replication
Induced mutations causes A-T and G-C transitions by incorporating into DNA and promoting mispairing
Replication slippage and base insertions
DNA polymerase slips on repetitive sequences, causing misalignment and insertion or deletion mutations.
Slippage induced insertions can disrupt reading frames, potentially leading to frameshift mutations and altered protein function
Describe nucleotide deletions and frameshift mutations
Frameshift (from deletions) shifts the reading frame, leading to altered amino acid sequences or premature stop codons = nonfunctional protein
Frameshifts in CRISPR-Cas9 editing: targeted nucleotide insertions or deletions introduced can cause frameshift mutations to knock out gene function for studying loss-of-function phenotypes
Phylogenetic dispersion of mutation rates
Can span several orders of magnitude. Different polymerases have distinct error rates. Organisms vary in the efficiency of their DNA repair systems. Factors like generation time, population size and reproductive mode can influence mutation rates.
Why does population size matter?
Organisms with larger pop tend to display lower mutation rates per nucleotide site. Better purging of deleterious mutations.
In small populations, random frequency changes can outweigh selection (genetic drift).
Explain genetic drift
Chance-driven changes in allele frequencies. Independently of allele’s impact on survival or reproduction. Genetic drift can reduce genetic diversity, leading to allele fixation or loss and shape evolutionary outcomes.
Describe silent and loud mutations
Base substitution mutations can be further categorised into synonymous (silent) and non synonymous because of redundancies in the genetic code
- Changes in the 1st or 2nd nucleotide of a codon almost always cause a change in the
amino acid. - Changes in the 3rd nucleotide of a codon of an amino acid rarely cause a change in the
amino acid
What is dN/dS
The ratio of non synonymous to synonymous substitution rates
=1, neutral evolution
>1, positive delection
<1, purifying seletion (removal of deleterious)
