In-Depth Notes on Mutations, Cell Communication, and Related Concepts

Exam Preparation and Office Hours

• Schedule for walk-ins regarding exam concepts:
  • Today: 3:30-5:00 PM
  • Tuesday: 10:30-Noon
  • Thursday: 9:30-11:00 AM

Types of Mutations

• Same sense mutations:

  • Change in a nucleotide (usually third position) that results in a different codon but specifies the same amino acid.
  • No effect on protein product or function.
  • Feature of the genetic code: Degeneracy allows for multiple codons to code for the same amino acid.

• Nonsense mutations:

  • Codon specifying an amino acid changes to a stop codon, causing premature termination of protein synthesis.
  • Results in a truncated protein that is usually inactive (null phenotype).

• Missense mutations:

  • Codon specifying one amino acid is changed to a codon for a different amino acid.
  • The effect on protein varies:
  • If the altered amino acid is not critical, the protein may retain full or partial function.
  • If it is critical, the protein is likely to be inactive.
  • Examples:
  • His/Arg vs. His/Asp in an active site.
  • Glu/Asp vs. Glu/Val in a soluble protein.
  • Sickle-cell anemia:
  • Caused by a single base pair substitution in β-globin, changing the charge of hemoglobin.
  • Affects 1 in 600 Black Americans; carriers are about 1 in 12.
  • High prevalence in tropical regions due to heterozygote advantage against malaria.

• Phenylketonuria (PKU):

  • Caused by a single amino acid change in a 451-amino acid enzyme, resulting in severe impairment unless treated by a special diet.

Codon Table and Amino Acid Changes

• Amino acid changes from base substitutions can be predicted using the codon table.
  • Possible changes occur within the same box, same position horizontally, or vertically.

Frameshift Mutations

• Definition:
  • Addition or removal of bases not divisible by three, disrupting the reading frame of mRNA.
• Result:
  • Changes all downstream codons and usually leads to premature stop codons (truncated proteins).
• Example:
  • Demonstrates how a single base addition can affect subsequent codon interpretation.
• In-frame mutations:
  • Removal of 3 bases results in the loss of one amino acid, may or may not affect function.
  • Cystic Fibrosis:
  • 70% of cases are due to a removal of a Phe codon, affecting the CFTR protein's ability to reach the membrane, leading to accumulation of Cl- ions and mucus problems affecting breathing.

Chromosomal-Level Mutations

• Some disorders caused by chromosomal-level mutations include:
  • Lymphomas and leukemias: caused by translocations.
  • Cancers: activated oncogenes due to duplications.
  • Fragile X syndrome and Huntington’s disease: caused by duplications of short repeated sequences.
  • Haemophilia A: often caused by insertions leading to loss of clotting factor VIII.
  • Duchenne's Muscular Dystrophy: caused by deletions.

The Ames Test for Mutagenicity

• Used to assess how many mutations a particular substance might cause, indicating potential carcinogenicity.

Important Concepts in Cell Communication

• **Types of Cell-to-Cell Communication:
  ** (details not provided in the transcript).
• Stages of a Response to a Signal:
  • Reception.
  • Transduction.
  • Response.
• Receptor-Ligand Interaction:
  • Each receptor has a specific Kd (dissociation constant), indicating affinity.
  • [Ligand] above Kd leads to greater response than [ligand] below Kd.
  • Ligand binding triggers conformational changes in the receptor, initiating effects.

Apoptosis: Programmed Cell Death

• Essential for:
  • Sculpting tissues.
  • Maintenance of organ size and shape.
  • Removal of damaged, worn-out, or infected cells.
• Two pathways of apoptosis:
  • Extrinsic pathway: Activated by external signals.
  • Intrinsic pathway: Involved mitochondrial signals and factors like p53.

Summary of Key Processes:

• Mitosis consists of five stages: Prophase, Prometaphase, Metaphase, Anaphase, and Telophase, each with distinct cellular events leading to division.
• The Eukaryotic Cell Cycle:Includes G1, S, G2, and M phases, varying time span based on organism and cell type.
• Protein Sorting Mechanisms: Includes co-translational and post-translational sorting, influenced by the site of translation, signaling sequences (NLS/NES).
• Transport Mechanisms: Through nuclear pore complexes (active for proteins >60 kDa requiring GTP).

Recommendations for Review

• Focus on understanding types of mutations and their impacts on protein function.
• Familiarize with cell communication pathways and processes involved in apoptosis, as these are essential for understanding cellular processes and responses.