5.6 - MUTATIONS

1. 5.6 - MUTATIONS • mutations (inherited DNA sequence errors) are mostly deleterious but can be beneficial and, indeed, are the engine of evolution through natural selection • eukaryotic (diploid) organisms can delay the consequences of mutations by having a copy of the gene to compensate • Types of Mutations • Point Mutations • (specific to one base pair) • Silent • alteration or deletion of introns on primary mRNA transcript •  no expression of mutation • third base of codon is replaced (by mutation or mistake in transcription) •  same amino acid is translated (wobble hypothesis), no expression of mutation

2. Substitution • Missense • alteration of codon (other than 3rd base) •  different amino acid in protein sequence (i.e. cystic fibrosis and sickle-cell anemia) • Nonsense • stop codon replaces one specifying an amino acid •  partial protein • produced (digested by proteases, often lethal)

3. Frameshift • Deletion(see CD Animation) • shift in reading frame results in removal of one or more nucleotides from DNA sequence • Insertion • shift in reading frame results in addition of a nucleotide •  insertion of many copies of the same codon is responsible for Fragile X (CGG on a noncoding region of X chromosome that gets longer in successive generations) and Huntingdon’s disease (CAG adds a string of glutamines to a coded protein, huntingtin, which accumulates in the brain) • indels all cause drastic alteration of protein structure resulting in a defective protein • (N.B. deletion or insertion of 3 nucleotides removes or adds one amino acid, not as serious as changing entire protein)

4. Translocation • simultaneous relocation of groups of base pairs between 2 (usually nonhomologous) chromosomes •  if unrelated gene sequences become contiguous, fusion protein function is altered or ceases (i.e some types of leukemia and Burkitt’s lymphoma) • consistently moving transposable elements (“jumping genes”) can disrupt transcription, inactivating a gene • Inversion • reversal of chromosome segment orientation •  possible disruption of gene or influence of other transcriptional control

5. Summary of Mutation Types

6. Causes of Genetic Mutations • spontaneous mutations result from missed base or two during proofreading, resulting in a point mutation • induced mutations result from exposure to mutagenic agents: • UV radiation has enough energy to cause point mutations, and has increased due to depletion of atmospheric ozone X rays can break the backbone of a DNA molecule and bases sometimes get lost as annealing enzymes repair DNA

7. pesticides have been linked to deleterious mutations, many are banned AIDS drugs resemble nitrogenous bases in DNA, insert themselves in HIV  DNA replication stops when DNA polymerase does not recognize chemical as a base ethidium bromide phosphoresces in DNA, used for DNA visualization in biotechnology, but can also bind to researcher’s DNA

8. Genetic Diseases • cancer is always a result of a mutation in the genetic sequence resulting in oncogenes (mutant versions of genes controlling cell growth and division) •  cystic fibrosis is caused by any of more than at least 60 different types of mutations of the CFTR gene (coding for a protein that transports chlorine across cell membranes), the most common being a 3-base-pair deletion (discovered at Sick Kids) • Section 5.6 Questions – P. 263, #1-8 • Chapter 5 Self-Quiz – P. 273, #1-6, 8-16 • Chapter 5 Review – P. 274-275, #1-8, 10, 11, 13-18, 21, 22