Genetics: Codons and Ribosomes Quiz

Molecular Basis of Gene Mutations

• Mutations are changes in DNA that impact genetic information.
• They can occur at the molecular or chromosomal level.
• Mutation effects vary greatly.
• Mutations are essential for evolution.
• A "mutant" refers to an organism with an unusual phenotype.

Types of Mutations

• Somatic Mutations: Occur in body cells (excluding germ cells).
  • Do not affect offspring.
• Germ-line Mutations: Occur in germ cells.
  • Can be transmitted to offspring.

Mutations in DNA Can Alter Proteins

• Examples of disease-causing mutations:
  • Beta-globin gene mutations (e.g., sickle cell disease) result in a base pair change in the beta-globin gene, causing the amino acid glutamic acid to become valine. This change distorts the structure of red blood cells.
  • Collagen mutations (deletions, insertions, RNA splicing mutations, single-base substitutions) are linked to common disorders like osteoarthritis, osteoporosis, and aortic aneurysms.
  • Alzheimer's disease mutations: mutations in the genes encoding APP, APOE, PSEN1, and PSEN2.

Mutations

• May occur spontaneously or due to exposure to radiation or chemicals (mutagens).

Spontaneous Mutation

• Not caused by exposure to known mutagens.
• Errors during DNA replication.
• Mismatched base pairs or loss of nucleotides during replication.

Induced Mutation

• Caused by mutagens, some of which are also carcinogens (cancer-causing).
• Radiations (e.g., UV light, X-rays).
• Chemicals (both natural and synthetic).
• Site-directed mutagenesis: a technique to create specific and intentional DNA sequence changes for research purposes.

Types of Mutations (Point Mutations)

• Point Mutation: A mistake changing a single base on a DNA molecule.
  • Transition: A pyrimidine replaces another pyrimidine (e.g., T to C) or a purine replaces another purine (e.g., A to G).
  • Transversion: A purine replaces a pyrimidine (e.g., A to T) or vice versa.
• Silent Mutation: Does not alter the amino acid coded for.
• Missense Mutation: Changes the codon, causing a substitution of an amino acid. This can alter or destroy protein function (e.g., sickle cell disease).
• Nonsense Mutation: Changes a codon for an amino acid into a stop codon. Results in a truncated, often nonfunctional protein.
• Insertion or Deletion Mutation: Addition or subtraction of a nucleotide not in multiples of 3 disrupts the reading frame of the gene.
  • Frameshift Mutation: Alters amino acids after the point of mutation, drastically changing the protein's structure and function.

Not all Mutations Affect Protein Function

• Silent Mutations: Do not affect the amino acid sequence, thus not impacting protein function.
• Example: AAA to AAG both code for lysine (same amino acid) => no change in protein.

Factors that can contribute to mutation rates:

• The cell's DNA repair mechanisms.
• The environment the cell is exposed to.
• Spontaneous DNA damage such as depurination and deamination.

DNA Repair Mechanisms

• Excision Repair: Removes damaged DNA segments.

  • Nucleotide excision repair: Removes 20-30 base segments of damaged DNA.
  • Base excision repair: Removes 1-5 bases, often caused by oxidative damage or chemical reactions.

• Mismatch Repair: Repairs errors introduced during DNA replication.

• Double-strand breaks:

  • Nonhomologous End Joining: Quickly repairs double-strand breaks in DNA, but may introduce deletions.
  • Homologous Recombination: More accurate, using sister chromatids for repair, but is slow

Co-Translational Protein Folding

• Proteins may start folding as they are synthesized by ribosomes, which influences its final functionality.

Molecular Chaperones

• Assist in protein folding, helping to correct misfolded proteins or direct them to the correct compartments.
• Types include HSP60, and HSP70- proteins
• These chaperones are important for proper biological functioning.

Protein synthesis by free and membrane-bound ribosomes

• Proteins targeted to different locations use free or membrane-bound ribosomes.
• Free ribosomes manufacture proteins intended for the cytoplasm.
• Membrane-bound ribosomes synthesize proteins destined for the endomembrane system (ER, Golgi, lysosomes, etc).

Protein Import

• Proteins are transported to their designated locations by various mechanisms, often involving signal sequences.

Summary

• This covers many aspects of DNA structure, function, and expression, from the molecular level up to whole-organism implications, so it's quite a broad topic.