Mutations and Fitness

Question 1

What are the 3 causes of point mutations?

Answer 1

UV damage
DNA breaks
Polymerase error

Question 2

What are the 5 ways you can fix a point mutation?

Answer 2

Polymerase proofreading
3’ to 5’ exonuclease (dnaG)
Base Excision Repair (BER)
Nucleotide Excision Repair (NER)
Methyl-directed Mismatch Repair (MMR)

Question 3

Loss of function mutations are dominant or recessive?

Answer 3

Recessive

Question 4

What are the 3 loss of function mutation classes?

Answer 4

Null
Hypomorph
Frameshift

Question 5

What are the 3 gain of function mutation classes?

Answer 5

Hypermorph
Dominant negative
Neomorph

Question 6

Gain of function mutations are dominant or recessive?

Answer 6

Dominant

Question 7

Dominant negative mutation

Answer 7

Gene prevents a WT protein from preforming (constitutive activation is a subtype)

Question 8

What are the 2 causes of insertions and deletions?

Answer 8

Pol 3 slippage
Recombination

Question 9

Explain pol 3 slippage

Answer 9

Inserts or deletes a single nucleotide when either the newly synthesized strand loops out (inserts) or the template strand loops out (deletes)

Question 10

Explain recombination induced indels

Answer 10

Homologous repeats meet. Plasmid is lost in a pure deletion. Fragment is moved in an insertion and thus deleted from its original place.

Question 11

Inversions vs indels

Answer 11

With inversions the gene order and direction is reversed

Question 12

Translocations

Answer 12

Homology leads to movement of a fragment

Question 13

Transposition

Answer 13

Movement of a transposon via transposase (tnp)

Question 14

Describe transposon structure

Answer 14

Direct repeats (same way) and inverted repeats are on either side of tnp (or more) gene(s)

Question 15

Explain how CRISPR works

Answer 15

2 RNAs are produced and hybridize
Cas9 is a nuclease that along with RNase3 processes the RNA hybrid
Cas9-RNA-hybrid scans for homologous RNA with a PAM
Homologous RNA cleaved

Question 16

What does CRISPR do?

Answer 16

Defense against viruses and transposons
Nonmethylated invading DNA is targeted by Cas1 and Cas2 guided by a PAM sequence
This makes spacer DNA which is sorta like bacterial memory B cells

Question 17

How do we use CRISPR?

Answer 17

Mutate region of interest randomly with no repair template and NonHomologous End Joining (NHEJ)

OR

You can synthesize a repair template to guide exactly how the DSB is fixed to introduce a specific mutation

Question 18

True or false: most mutations will never be observed due to selection and multiple competent sub populations

Answer 18

True

Question 19

What are the 3 evolutionary effects of mutations

Answer 19

Detrimental
Neutral
Beneficial

Question 20

True or false: mutations can only be spontaneous, not induced by selection

Answer 20

False, they can be both