5 Mutations and Genetic Diversity Flashcards
Mutation definition
A permant change in the DNA sequence
Inherited change in the sequence - after cell division (mitosis) / in germ line cells in multicellular organisms
Diversity in meiosis
mutations may or may not change the phenotype of an organism
DNA damage vs mutation
Potentially any change to the DNA sequence
Errors such as misincoperation OR chemical damage (deamination of cytosine / oxidation / UV / radiation)
Deamination (of C —> U)
Mismatch of U-G can be removed and repaired back to a C-G (original sequence)
Advantage of double stranded DNA and complementary base pairing, as long as theres only damage on 1 strand you can use the other undamaged strand to repair it
Damage vs Mutation
Damage - can be repaired
Mutation - cant be repaired
Because pairing has occurred and the U has been changed to a T so instead of G-C base pairing theres now A-T base pairing…
no way for the cell to tell that this is wrong as T and A are complementary its just the wrong base pairing due to the change in the C (contains a permanent alteration - MUTATION)
Types of DNA damage - Misincoperation
in operation relies on base pairing - but this is imperfect - 1 in 10^4/^5 is incorrect
Wrong nucleotide as phosphodiester bond made between wrong nucleotide
Proofreading 3’—>5’ exonucelus removed misincoperates nucleotides (all but 1 in 1000)
Types of DNA damage - Mismatch repair
Wrong pairing in daughter helix (eg. A-G) because theyre mismatched a kink is formed in the helix, proteins will identify this and bacteria (called Mut S) it will detect the template strand as the template strand is bound to methyl groups but daughter strand doesn’t have methyl groups until after replication.
- Protein called Mut L, bridges the gap while Mut S works to replace the mismatch
- Mut H protein identifies the new strand by lack of methylation
- DNA polymerase and ligase replace the section
Types of DNA damage - alkylation
Addition of alkyl / methyl / ethyl group on the oxygen at one position of the base ring - changes base pairing
Types of DNA damage - depuration
Removal of G or A from the sugar (purines) - loss of an entire base
Pyrimidine dimers - arises from UV light
2 pyrimidines (usually thymines) absorb the light and end up forming a cyclone butane (circular chain between the 2 thymines) and this causes a kink in the strand and leads to misincoperation of nucleotides on the opposite strand if replication occurs before this is repaired
Photolyase can reverse this step (not present in mammals)
Repair types (2)
Base excision repair —> first removal of base by a glycolysae
Nucleotide excision repair —> removal of a section of 1 strand
What do SSB and DSB stand for
SSB - single strand breaks
DSB - double strand breaks
SSB and DSB repair (which one should be easier to repair in principle)
SSB are straightforward in principle to repair however SSB can lead to DSB which is harder to repair
—> just rejoining the ends can lead to errors such as insertions, deletions or miss joining which lead to rearrangements or transformations
Repair by homology
Under certain circumstances an identical (or related) double strand is available to contribute to repair
This is because after replication you have 2 copies of the double strand OR using a homologous chromome
Programmed cell death (apoptosis)
Can be a repsonse to failure to repair DNA and prevents the cell dividing (mitosis) and leads to ‘safe’ disposal of the cell
Point mutations
Usually changes 3rd position of the codon make no difference to the AA coded for (silent mutation)
Changes to the 1st position of a codon very often lead to conservative replacement - AA replaced by a similar AA (eg. Replacing 1 hydrophobic AA with another hydrophobic AA) so creates minimal difference
Frameshift mutations
Insertions and deletions that arent groups of 3 nucleotides
Genetic disease example from mutation
Point mutations can if inherited give rise to genetic diseases such as Phenylketonuria
Regulatory mutations
Mutations here could affect how proteins interact with DNA or the expression of different porteins and wether theyre expressed in different tissues
Mutations don’t have to be in the coding sequence to affect the expression of particular genes
Can affect phenotype and give rise to disease
Mutations and cancer
Mutations can lead to dysregulation of cell division
Cancer can also result from failure of DNA repair
Example BRCA1/2 breast cancer susceptibility
Products of the BRCA 1/2 are involved in DSB by homologous recombination…
More error prone way of just joining ends will occur if theres a mutation in the BRCA 1/2 genes
Joining ends that possible have errors including insertions / deletions / translocations which may give rise to cancer cells by changing the genome
Possible to manipulate DNA repair
BRCA 1/2 treatment
Treat by inhibiting SSB repair - PARP inhibitors which means almost no repair is possible resulting in apoptosis - triggers cancer cells to undergo apoptosis
What do mutations contribute to
Mutraions contribute to genetic diversity which powers evolution.
In eukaryotes, meiosis is a major contributor to genetic diversity.
