🧟 DNA Mutations

Importance of Mutations

• Sustain life but also cause suffering

  • Source of all genetic variation (providing raw material for evolution)

  • Source of diseases/disorders

• Useful for probing fundamental biological processes

  • Identifying mutant genes that alter development are useful for identifying function of gene

  • When mutant genes alter development, they help scientists figure out what normal processes or structures require the gene to function properly

  • e.g. Wnt genes involved in patterning of vertebrate axis are now known to be at the center of colon cancer

Somatic/Germ-Line Mutations - NOT TESTED

• Somatic

  • Occur in nonreproductive cells

  • Are passed to new cells through mitosis, creating clone of cells with mutant gene

  • e.g. Melanoma

• Germ-line

  • Occur in cells that give rise to gametes

Meiosis/sexual reproduction allow germ-line mutations to be passed to ~half of next generation, who will have the mutation in all of their cells

Types of Gene Mutations

• Base substitutions

  • Transition

  • Transversion

• Insertions/Deletions

  • Frameshift mutations

  • In-frame insertions/deletions

• Expanding nucleotide repeats

  • Increase # of copies of set of nucleotides

Substitutions - Transitions

• Like for like

  • Purine to purine (A to G, G to A)

  • Prymidine to prymidine (T to C, C to T)

Substitutions - Transversions

• Like for non-like (switching versions)

• Purine to pyrimidine (A to T)

• Pyrmidine to purine (T to G)

Base Substitutions

• One codon changed when a base is added, no frameshift, only that codon is affected

Frameshift - Base Insertions

• Base is inserted and entire frame shifts, altering every codon after the insertion

Frameshift - Base Deletions

• Base is deleted and entire frame shifts, altering every codon after deletion

Expanding Nucleotide Repeats

• e.g. CAG is normally repeated 12 times, but mutation causes 300 repeats instead

• Repeats increase with generations (i.e. Parent might have 300 repeats, child will have 4000)

1. DNA has 8 copies of CAG

2. Strands separate and replicate

3. Hairpin forms on synthesized strand

4. Part of the template ends up being repeated on the synthesized strand

5. DNA strands separate

6. Strand with extra CAG repeats becomes template for replication

7. Resulting DNA molecule contains extra copies of repeats

Phenotypic Effects of Mutations

• Forward - Wild to mutant

• Reverse - Mutant to wild

• Missense - Amino acid to another amino acid

• Nonsense - Sense codon to stop codon

• Silent mutation - Codon to another codon that codes for the same amino acid

• Neutral mutation - No change in function (e.g. many amino acids have the same properties/functions, so mutations don’t affect the protein too much)

Forward Mutation

• Wild type to mutant

Reverse Mutations

• Mutant to wild type

Missense Mutations

• Amino acid to another amino acid

Silent Mutations

• Codon to another codon that codes for the same amino acid

Neutral Mutations

• No change in function (e.g. many amino acids have the same properties/functions, so mutations don’t affect the protein too much)