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.