Translation mutations Flashcards
When can the gDNA or mRNA sequence be altered?
Errors can occur during DNA replication.
If not corrected, the genomic sequence can be permanently altered and inherited in the next cell generation.
What are mutations of nucleotides?
A proton shift causes the common form of nucleotide to become a rare form.
How does a mutation affect thymine?
How does a mutation affect guanine?
How does a mutation affect cytosine?
How does a mutation affect adenine?
How do hydrogen bonds usually form?
When adenine and thymine, or guanine and cytosine form hydrogen bonds, there is a set distance between the bases, causing a specific twist in the DNA.
What happens to the hydrogen bonding when there is a mutation?
If a rare form of nucleotide binds to a normal form, it causes a change in hydrogen bonding and causes the pair to take up a different spatial place in the nucleus.
What is strand slippage?
The stability is off during replication.
It is a wobble, which is enough for a permanent change, if proof reading from polymerase does not correct it.
How often does DNA polymerase make mistakes?
At a rate of 1 per every 100,000 molecules.
If uncorrected, with 6 billion base pairs in each diploid cell, this would create 120,000 mistakes every time a cell divides.
How does DNA polymerase proof read DNA?
DNA polymerase runs in a 5’-3’ direction when replicating.
2 polymerases also have exonuclease activity in a 3’-5’ direction, so checks that the correct nucleases have been laid down.
Which types of DNA polymerase have proof reading machinery?
Gamma and delta polymerase in the mitochondria.
What is mismatch repair?
In this process some mistakes are corrected after replication.
When an incorrect nucleotide is added to the growing strand, replication is stalled - the nucleotide’s exposed 3’OH group is in the wrong position.
What happens to mistakes after the mismatch repair process?
Incorrectly paired nucleotides that still remain following mismatch repair become permanent mutations after the next cell division.
This is because the cell no longer recognises them as errors.
What can happen if there is strand slippage on the new strand?
The newly synthesised strand loops out, and one nucleotide is added to the strand.
The new strand has an extra nucleotide.
What can happen if there is strand slippage on the template strand?
The template strand loops out.
One nucleotide is omitted on the new strand.
The new strand is missing a nucleotide.
What is eukaryotic gene structure?
Where can mutations in genes not have a big effect?
The upstream intergenic region is the space between one gene and the next gene - non-coding and untranslated.
The untranscribed region is also untranslated.
So there is little effect.
Where can a mutation in the gene have a big effect?
In the promoter region.
In sites between the exon and intron borders.
How can mutations affect the promoter region?
If a mutation is in the intergenic regions, chances of having an effect are low.
If the mutation is in the GC box, CCAAT box or TATA box - there is a high chance of the mutation having a greater effect.
If in the transcription start site - 100% chance.
What is the effect of mutations on introns and exons?
If the mutation is in the specific sequence of the intron/exon border - where snRNAs bind - then introns won’t be spliced out.
How can mutations occur?
Variations in the nucleotide sequence of a genome can occur because of physical damage to the DNA.
This is induced or spontaneous.
What are induced mutations?
Environmental agents:
Exposure to chemicals
UV rays - which damages DNA as it is on the skin’s surface.
What are spontaneous mutations?
Without any exposure to any environmental agent:
Spontaneous biochemical reactions taking place within the cell
Wobble-induced/replication errors.
What are the types of mutation?
Point mutation of a single base pair - leading to substitutions - transition or transversion.
What are transition substitution mutations?
Purine replaced by a purine.
Adenine –> guanine.
Pyrmidine replaced by a pyrimidine.
Thymine –> Cytosine.
What are transversion substitution mutations?
Purine replaced by a pyrimidine.
Pyrimidine replaced by a purine.
What are the types of mutations that can occur from substitutions?
Silent
Missense
Nonsense
What are silent mutations?
No change in the protein sequence
What are missense mutations?
Changes the amino acid sequence
What are nonsense mutations?
Introduces a stop codon too early
What effect does a nonsense mutation have?
It creates a stop codon too early, so the peptide cannot be folded correctly into the protein, and has no function.
What effect does a missense mutation have?
Different nucleotides causes a different amino acid to be made.
This can have an impact depending on different factors - whether the new amino acid is in the same group as the original - (hydrophobic, small etc).
What are point deletion mutations?
A deletion early in the sequence causes a frameshift missense mutation.
A deletion at the stop codon causes extensive missense, as the stop signal is deleted, so the protein is very long and different from the original.
What happens if 1 or 2 bases are deleted?
Frameshift causing extensive missense.
Frameshift nonsense.
What happens if 3 bases are deleted?
No frameshift causing missense.
No frameshift causing nonsense.
What are conservative changes?
Results in the substitution of similar but not identical amino acids.
What are non-conservative changes?
Results in the substitution of a different amino acid with different biochemical property.
