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What is Mutation?

Mutation- an inherited change in genetic information

• If the sequence of DNA is changed then the function of a geene and expressed phenotype may change

• a mutation can be inherited from cell to cell as a result of mitosis (somatic) or generation to generation from parents to offspring (germ-line).

• Mutation is the source of all genetic variation, including disease and adaptations

What Types of Mutations are there?

Chromosomal Mutations

Point Mutation (SNPs)

Repeat Expansions

Insertions/ deletions

Epigenetic “Mutations”

What Causes Mutations?

• Induced: caused by environmental factor

  • UV light

  • Radiation

  • Chemical

• Spontaneous: not external cause, naturally occurring errors; die to error from natural processes

  • Selfish genetic elements

  • Error in DNA repair

  • Error in replication

• Anomalous base pairing and Spontaneous base changes causes point mutations

Spontaneous Mutations

Base Changes

• Transversion mutation- exchange if nucleotides outside family, purine for pyrimidine

• Transition mutation- exchange a purine for a purine or a pyrimidine for a pyrimidine (more frequent)

Anomalous Base Pairing

• Incorporated error is an error not fixed→ these will become a replicated error (point mutation) SNP (can still be fixed but after second round of replication it will go undetected)

Chemical Changes

• Rare bases

• Deamination→ usually results in a transition mutation

• Depurination

Base Excision Repair

(go back to slides and read this- pg 28)

• Similar to the process that removes and replaces RNA primers during
  DNA replication (DNA pol I is the polymerase)

Depurination: Loss of Purine

• the nitrogenous base breaks off

• Dna pol typically fixes this by just putting an A- example of transversion

Repeat Expansions

• Example of a disease caused by this is Huntington’s Disease

• these happen during DNA Replication

• a structure is formed called a hairpin loop where the DNA strand kinda folds back on itself and base pairs with itself

Induced Mutations

• Induced: mutations cause or induced by external factors (mutagens) usually chemical or environmental, which cause a nucleotide change

• Chemicals that interact w/ DNA, including
  • Artificial deamination
  • Base analogs- Artificial, not naturally occurring base that can act like a thymine
  • Intercalating agents- fits between the bases and causes breaks in the DNA strands (some found in cigarette smoke)

  • Induces indels and causes frameshift mutations

• Radiation- Radioactive isotopes, X-rays, and UV
  • Direct- UV rays that cause Pyrimidine Dimers
  • Free Radicals- interact and react with the phosphate bonds of DNA and causing DNA breaks (the repair of this DNA break (non-homologous end joining) is in itself mutagenic)

How are Errors Fixed?

• Random events happen and mutagens are constantly attacking your DNA- yet overall low mutation rate bc the existence of many repair mechanisms

Direct replacement during Replication:

• DNA polymerase has a proofreading mechanism →

• Exonuclease removal of mismatched base pair

Repair after Replication

• Base Excision repair (BER) (used to repair small DNA lesions)

• Nucleotide excision repair (used to repair UV damage

• Mismatch repair