5 Mutations and Genetic Diversity

Question 1

Mutation definition

Answer 1

A permant change in the DNA sequence

Inherited change in the sequence - after cell division (mitosis) / in germ line cells in multicellular organisms

Question 2

Diversity in meiosis

Answer 2

mutations may or may not change the phenotype of an organism

Question 3

DNA damage vs mutation

Answer 3

Potentially any change to the DNA sequence
Errors such as misincoperation OR chemical damage (deamination of cytosine / oxidation / UV / radiation)

Question 4

Deamination (of C —> U)

Answer 4

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

Question 5

Damage vs Mutation

Answer 5

Damage - can be repaired

Mutation - cant be repaired

Question 6

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…

Answer 6

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)

Question 7

Types of DNA damage - Misincoperation

Answer 7

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)

Question 8

Types of DNA damage - Mismatch repair

Answer 8

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.

1. Protein called Mut L, bridges the gap while Mut S works to replace the mismatch
2. Mut H protein identifies the new strand by lack of methylation
3. DNA polymerase and ligase replace the section

Question 9

Types of DNA damage - alkylation

Answer 9

Addition of alkyl / methyl / ethyl group on the oxygen at one position of the base ring - changes base pairing

Question 10

Types of DNA damage - depuration

Answer 10

Removal of G or A from the sugar (purines) - loss of an entire base

Question 11

Pyrimidine dimers - arises from UV light

Answer 11

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)

Question 12

Repair types (2)

Answer 12

Base excision repair —> first removal of base by a glycolysae

Nucleotide excision repair —> removal of a section of 1 strand

Question 13

What do SSB and DSB stand for

Answer 13

SSB - single strand breaks

DSB - double strand breaks

Question 14

SSB and DSB repair (which one should be easier to repair in principle)

Answer 14

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

Question 15

Repair by homology

Answer 15

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

Question 16

Programmed cell death (apoptosis)

Answer 16

Can be a repsonse to failure to repair DNA and prevents the cell dividing (mitosis) and leads to ‘safe’ disposal of the cell

Question 17

Point mutations

Answer 17

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

Question 18

Frameshift mutations

Answer 18

Insertions and deletions that arent groups of 3 nucleotides

Question 19

Genetic disease example from mutation

Answer 19

Point mutations can if inherited give rise to genetic diseases such as Phenylketonuria

Question 20

Regulatory mutations

Answer 20

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

Question 21

Mutations and cancer

Answer 21

Mutations can lead to dysregulation of cell division

Cancer can also result from failure of DNA repair

Example BRCA1/2 breast cancer susceptibility

Question 22

Products of the BRCA 1/2 are involved in DSB by homologous recombination…

Answer 22

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

Question 23

Possible to manipulate DNA repair

Answer 23

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

Question 24

What do mutations contribute to

Answer 24

Mutraions contribute to genetic diversity which powers evolution.

In eukaryotes, meiosis is a major contributor to genetic diversity.