Mutations

Question 1

Mutations

Answer 1

in genes are random and their occurrence is rare

Question 2

Mutation rate

Answer 2

Mutations per unit time

Question 3

What are the 2 way mutation rate is measured?

Answer 3

at the phenotypic level, by counting the number of mutations affecting a phenotype; and at the molecular level, by deter- mining the frequency of mutations per base pair.

Question 4

Measured at the phenotypic level

Answer 4

Number of mutations affecting a phenotype

~10-6 to 10-8 per gene

Question 5

Measured at the molecular level

Answer 5

Frequency of mutations per base pair( certain base pairs within genes have higher mutation rates than others)

Things mutate at different rates according to where in the genome it is and the environmental factors affecting it

~10-9 per replicated base pair

Everyone in their cells have multiple mutation rates depending on the genes involved and specific cell types

Question 6

mutation hotspots

Answer 6

Some genes mutate more than others
Larger genes mutate more than smaller genes because they have more nucleotides contained in their gene region

Ex. Human X-linked dystrophin (DYS) mutates at ~10-4

Question 7

Germ-line mutations

Answer 7

Mutations are passed from one generation to the next

i.e. mutations that occur in genes and passed down via gametes

Mendel’s experiments with traits in peas are germ-line mutations

In sex cells and stem cells

This how we get phenotypes to change within population

Question 8

Somatic mutations

Answer 8

Can be passed to future generations of cells in a cell lineage due to mitosis

BUT not passed to passed to further generations

Only direct descendants of the cells carrying the gene mutation

Only occurs in individual and cannot be passed down because it doesn’t occur in sex cell

Surrounding cells that result due to mitosis will get the mutation

Ex- cancer, cant be passed on to child

Question 9

Point mutations

Answer 9

Confined to a specific base pair or gene location (changing one nucleotide to another nucleotide)

Add, delete, or substitute one or more base pairs

Can occur anywhere in the genome

Several kinds of point mutations

Question 10

what is point mutations occurring in the coding sequence of a gene (in exons)

Answer 10

Could change the amino acid sequence- we will have different protein that has reduced different or no function

Question 11

what happens if point mutation is occurring in the regulatory sequence of a gene (enhancers, repressors, etc.)

Answer 11

Could change the amount of gene expressed (ie less or more protein product) doesn’t change structure of protein

Question 12

How do we describe coding sequence mutations?

Answer 12

based on “levels”

Amino acid level
RNA level
DNA level

Question 13

Which mutations occur at the amino acid level?

Answer 13

is an amino acid change in the sequence? What was the effect?

Synonymous(amino acid stayed the same a mutation occurred but the leucine is still a leucine), nonsynonymous (amino acid changes)

We usually use these to describe the change/effect in the amino acid sequence

Question 14

Which mutations occur at the RNA level?

Answer 14

did a nucleotide change that resulted in an amino acid change? (how did the codon change)

Missense(causes the amino acid to change), silent(codon will still code for the same amino acid but nucleotide changed),

nonsense(takes a codon that was coding for a amino acid and now codes for a stop codon, premature stoppage of polypeptide chain ),

nonstop(normally had a stop codon but it mutated and we no longer have the stop codon)

We usually use these to describe the change/effect in the codon

Question 15

Which mutations occur at the DNA level?

Answer 15

How did the nucleotide change?(looking at the A G C T u)

Substitutions (transition, transversion), insertion/deletions (frameshifts)

We usually use these to describe the change in the nucleotides

*NOTE: All of these are a result of a change in the nucleotide sequence , which could affect the amino acid sequence

Question 16

What are some examples of regulatory mutations?

Answer 16

Promotor mutation-> affects the timing or amount of transcription(early late, transcription)

Polyadenylation mutation-> alters sequence of mRNA

Splice site mutation -> improperly keeps an intron or removes an exon

DNA replication mutation -> Increases number of short DNA repeats

Question 17

Is having a mutation a bad thing?

Answer 17

Having mutations is not a bad thing all the time because it means we have differences in our alleles and that allows populations to evolve and adapt

We can speed up mutations by being exposed to toxic chemicals uv lights radiation

Question 18

Base-pair substitutions

Answer 18

are a type of point mutation, generally described at the DNA level
replacement of one nucleotide base pair by another is

Question 19

What are the types of base pair subsitutions?

Answer 19

Transition and transversion

Question 20

Transition mutations

Answer 20

purine replaces a purine (A->G, G->A)

Pyrimidine replaces a pyrimidine (C->T, T->C or C->U, U->C (in RNA))

Most common since amino acid codons generally allow for the 3rd wobble position to mutate -> results in synonymous mutations

A codon ending with a purine, when changed to the other purine, will generally still code for the same amino acid (same scenario with pyrimidine-ending codons)

Question 21

Transversion mutations

Answer 21

Purine replaces a pyrimidine

Pyrimidine replaces a purine

Common with nonsynomonous

Question 22

Silent mutations or synonymous mutations,

Answer 22

A base-pair substitution that produces an mRNA codon that specifies the same amino acid as the wild-type mRNA

Most common as a result of transition mutations (purine to purine)

Will produce synonymous effects at the amino acid level

Can be beneficial since they do not alter function but can create genetic diversity

Considered a neutral mutation since it does not affect the function of the protein

Question 23

Give an example of a silent mutation:

Answer 23

a silent mutation at the RNA level will result in synonymous mutations, at amino acid level, Leucine if we change 3rd wobble position from a U to a C we still have a leucine amino acid doesn’t change and overall function of polypeptide doesn’t change, protein folding and shape doesn’t change, it increases genetic variation at nucleotide level )

if a mutation changes a acidic amino acid in the polypeptide to another acidic amino acid we would still consider it a neutral mutation because it doesn’t affect shape and function

Neutral doesn’t affect function even if amino acid can change sometimes

Question 24

Missense mutation

Answer 24

A base-pair substitution that results in an amino acid change

• Ie the effect is nonsynonymous (not similar amino acid)
• Usually a result of transversions

Protein function may be altered by a change in the amino acid sequence

• Could be a neutral mutation if it does not affect the function of the protein
• As long as the amino acid is in the same class as the one it got changed from it will have same function- ex- acidic amino acid to a different acidic amino acid

Question 25

Nonsense mutation

Answer 25

A base-pair substitution that results in a premature stop
- Ie the effect is nonsynonymous in the amino acid sequence

• Protein function is altered by a premature termination of translation

A nonsense mutation is never neutral

Question 26

Nonstop mutations

Answer 26

A point mutation that occurs within a stop codon, changing it to code for an amino acid

Prevents the amino acid polypeptide from terminating properly, altering protein structure and function

Never neutral

Question 27

Neutral mutations

Answer 27

Can be a result of silent mutations (amino acid stays the same)

Can also be a result of changing one amino acid to another similar amino acid

A polar amino acid to another polar amino acid

A nonpolar amino acid to another nonpolar amino acid

A basic amino acid to another basic amino acid

An acidic amino acid to another acidic amino acid

Overall protein structure and function remains the same

Question 28

Frameshift mutations

Answer 28

Insertions/Deletions of one or more nucleotides within the coding sequence of a gene leads to an addition or removal of mRNA nucleotides

• Alters the reading frame (genetic code never skips a nucleotide and never skips a codon)
• Results in an altered amino acid sequence from the point mutation to the end of the amino acid sequence
• Frequently generate premature stop codons (it would be a nonsense mutation as a result of a frameshift)
• Result in complete loss of protein structure and function

Ex- at DNA level an insertion or deletion resulted in frameshift that at the RNA level we have a nonsense mutation, amino acid level it a nonsynonymous mutation

Question 29

Regulatory Mutations

Answer 29

Occur in noncoding regions of genes
Promotors
Introns
5’UTR/3’UTR

Don’t change protein structure or function, change level of transcription (thing can be up regulated or over expressed, making more than you need, down regulated or under expressed your not making enough)

Every organism requires a proper amount of gene product to function and if we don’t have enough of the gene product it can cause phenotypic changes in individual

Can lead to production of abnormal or abnormal amounts of mRNAs, producing mutant phenotypes

Question 30

What are 3 common regulatory mutations ?

Answer 30

Promoter mutations

Splicing mutations

Cryptic splice sites

Question 31

Promotor mutations

Answer 31

occurs in promoter region, everything needs to be bound to the promoter region in order for timely and proper gene transcription)

Alter consensus sequence nucleotides and interferes with efficient transcription initiation

Question 32

What is an example of a promoter mutation?

Answer 32

Ex β-hemoglobin gene has many promotor mutations that reduce transcription efficiency, reducing the amount of β-hemoglobin protein produced

Question 33

Splicing mutations (introns and exons)

Answer 33

In the coding strand of βhemoglobin gene, a GT occurs at the 5’ splice site (splice sites are specific sequences within an intron that is adjacent to an exon that is going to tell specialized enzymes okay we need to cut here to remove intron and glue exon here)

An AG at the 3’ end of the exon

• Denotes were the end of the exon and the start of the intron is
• Allows formation of the spliceosome at this consensus sequence

Changing this consensus sequence in β-hemoglobin gene either reduces intron splicing(the enzyme that is going to cut the mrna is not going to recognize it completely so its not going to cut it effectively) or eliminated intron splicing at this site

Can alter protein shape and function (if intron is left in or not cut out properly the protein shape will be affected because they will get read during translation because codons are never skipped)

Question 34

Cryptic splicing sites

Answer 34

Certain base-pair substitutions create new splice sites that replace or compete the authentic splice sites in pre-mRNA processing

In β-hemoglobin gene, intron 1 is ~130 bp long
- A substitution that changes G to A at position 110 in intro 1 creates an AG dinucleotide that is a cryptic splice site (changing it to an AG creates that recognition sit which usually denotes the end of an exon, so splicing enzyme will think its end of exon 1 and start cutting but it was actually not end of exon)

• Intro of accidental splice sites (cut things inappropriately)
• Only 90% of intron 1 is spliced out, leaving an additional 19 bp in the mature mRNA
• Change amino acid sequence- and protein form and function

Question 35

Why are mutations important?

Answer 35

Increases genetic variation

• Changes in DNA provide the source of genetic variation
• It’s random!

Point mutations affect phenotypes by changing the amino acid sequence

• Ultimately changes the protein structure and function
• Interactions of different R groups

Can be caused by a variety of factors

• Mutagens -> agents that cause mutation (induced mutations)
• Ex. ROS, radiation, chemicals, UV light
• Increase mutation rates and/or interfere with repair mechanisms

Naturally-occurring replication errors (spontaneous mutations)