Lesson 20: Mutation 1

What is the source of all new genetic variation

Mutations

What are mutations? What do they have the potential to change?

• mutations are an inherited change to the DNA sequence (genetic information)

• Have the potential to change the expression (via mutation in regulatory regions) or function (via mutations in coding region) of the encoded protien that cansues a change in the phenotype

Are mutations always negative to the organism

No they can be negative, neutral, or positive

How much of human DNA is noncoding? What does that mean for most mutations? 

98% of human DNA is non coding for protiens so most mutations do not change a protein 

Describe gene mutations (scale, how many genes it affects, how it was originally revealed)

Small scale changes in DNA sequence

affects a single gene

Originally revealed through studies of phenotypic effects

Describe chromosome mutations (scale, how many genes it affects, how it was originally revealed)

large scale changes in DNA organization/amount of DNA ect…

Affect chromosomal structure or number

Often can be visualized via microscopy ex. karotype 

How are both types revealed now

By DNA sequencing

Where can mutations occur in cells

Cab occur in somatic or germ line cells

Describe the difference between somatic and germ line mutations

Somatic means non reproductive cells, so the mutations are not passed to the next generation. They influence local behavior of the cells within the organsm, but it won’t be passed down to daughter cells. Most types of cancer are somatic 

Germ line means sex cells, so the mutations can be inherited and passed to the next generation . Germline cell will generate gametes, if those gamests fuse with another mutant gamete, it can get shown.passed to offsrping. 

What are the three ways to classify gene mutations

• phenotypic effects of mutations

• Causative agent of mutation: What generates the mutation

• Molecular nature of mutation: what is the consequence of the mutation on the molecular structure of the gene itself

Gene mutations: Describe base substitution

• Simplest type of mutation - one base is converted to another, but just bc it is the siplest doesn’t mean its the most frequent

What is transition base substitution and give examples

When a purine is replaced by a purine (A to G or G to A)

Or when a pyrimidine is replaced by a pyrimidine (C to T or T to C)

What is transversion base substitution

When a purine is replcaed by a pyrimidine (A to C, or A to T, or G to C, or G to T)

Or when a pyrimidine is replaced by a purine (C to A, or C to G, or T to A, or T to G)

Gene mutations: describe insertions and deletions 

Addition or removal of one or more bases, termed as Indels 

Gene mutations: indels. How common are they

Indels are more common than base substitutions

What can indel mutations lead to

Can lead to frameshift mutations if numbers of nucleotides that are inserted or deleted aren’t in groups of three

What do frameshift mutations change/inducre

Change downstream protein sequence or may induce a premature stop codon

Gene mutation: What are expanding nucleotide repeats associated with

Asspciated with more than 50 human diseases ex. huntingtons and some types of ALS 

What is the common nucleotide repeat in expanding nucleotide repeat mutations and how many repeats can there be

Repeat is often of the trinulceotide CNG where N is any nucleotide

number of repeats can increase from few to up to 1,000+

Describe one model of expanding nucleotide repeats

1. A DNA molecule has mutiple CAG repeats 

2. The two strands seperate 

3. ANd replicate 

4. During replication, a hairpin forms on the newly synthesized strand 

5. Casuing part of the template strand to be replicated twice and increasing the number of repeats on the newly synthesized strand 

6. The two strands of the new DNA seperate

7. The strand with the extra CAG cope serves as a template for replicatio

8. Resulting DNA molecule contains additional copeis of the CAG repeat 

Expanding nucleotide repeats isn’t fully understood 

What does wild type mean

the original, normal DNA sequence

Functional effects of mutations: What does a forward mutation do

Causes a change in phenotype

Functional effects of mutations: What does a reverse mutation do

Reverts the change in phenotype back to wildtype

Functional effects of mutations: what does a loss of function mutation do

causes complete/partial absence of protein function

Functional effects of mutations: What does a gain of function mutation do

Results in the production of protein whos function is not bormally expressed. ould cause more activity making the cell do something different. Protein could also be expressed at a diffferent location/time (Inapproporitate expression/production)

Functional effects of mutations: What does a conditional mutation do

Functions/does not function depnding on conditions (ex. temp) usually involved protein structure change 

Functional effects of mutations: what is a lethal mutation do

results in imediate or prematrue death 

Functional effects of mutations: what does s supressor mutation do

hides or supresses the effect of another mutation

What is a missense base substitution

The new codon encodes for a different amino aicd, there is a change in the amino acid seqeunce

What is a nonsense base mutation

The new codon formed is a stop codon. There is a premature termination of translation

What is a silent base mutation

THe new codon encodes for the same amino acid, there is no change in amino acid sequence

Using an example, expalin the difference between forwards, reverse, and supressor mutations

Say the genotype for red eyes is A+ B+. A forward mutation changes the wild type into a mutant phenotype by causing a mutation in the A+ allele by turning it into A-. A reverse mtuation would change the A- allele back to A+, restoring the wild type gene and phenotype. A supressor mutation would change the B+ allele to B-, so there is now an A- B- geneotype. THat produced an organism which a different genotype that contains the original mutation and the supressor mutation but has wild type phenotype.

What is an intrageinc supressor mutation 

A change in the same gene, just somewhere else 

What is an intergenic supressor mutation 

A mutation between genes 

Define the rate of mutation/ What is it applied to? How is it expressed? Why is it important?

The frequency with which a wild type allele changes to a mutant allele. It applies to a singal gene or the whole genome. It can be expressed per cell division or gamete or round of replication or generation. Rate of mutation is important bc it deals with likelihood of changes occuring and how differnt genes and different organisms have different rates of mutation. 

What is the rate of mutation affected by. What is intrinsic mutation

How often a change to the DNA takes place (intrinsic rate of mutation) Wheter or not the change jhas been repaired. Wheter or not that change is detected (if the phenotype hasn’t changes, it is ahrd to detect. How likley the organism is to be exposed to mutagens. 

What is a mutational hotspot

Rates within an organism vary across genome. There are certain sequences that have higher rates of mutation than others

What does DNA sequencing suggest about rates of mutation?

Suggests that rates occur faster than originally though from orginial studies that depended on phenotype changes. DNA sequencing shows the entire sequence, rather than surface level phenotypic studies.