Topic 8 - gene expression

Mutations

• Gene mutation: alteration of one gene’s base sequence, often during DNA replication (S phase).

• Mutations occur spontaneously; frequency increased by mutagens (carcinogens, UV, ionizing radiation).

• Effect on proteins: changed base sequence → altered amino acid sequence → altered tertiary structure → changed function (possibly nonfunctional).

• Some mutations can lead to cancer.

• Main mutation types (affecting coding sequence):

  • Addition (insertion): extra base → frameshift to the right → many codons altered → likely nonfunctional protein.

  • Deletion: base removed → frameshift to the left → many codons altered → likely nonfunctional protein.

  • Substitution: one base swapped → affects single codon; due to degeneracy may be silent.

  • Inversion: segment detaches and reinserts reversed → codes different amino acids for that segment.

  • Duplication: base(s) duplicated → frameshift (if single-base) → downstream codons altered.

  • Translocation: segment moves to another chromosome → large changes in gene expression and phenotype.

Key terms

• Gene mutation: change in DNA base sequence of a single gene.

• Frameshift: shift in reading frame due to insertion/deletion, altering downstream codons.

• Degenerate code: multiple codons code for same amino acid.

• Promoter/terminator: DNA sequences required for correct transcription initiation and termination.

Term	Definition
Stem Cell (undifferentiated)	Cell that can continuously divide and differentiate into specialized cells.
Totipotent	Can produce any body cell; present briefly in early embryo.
Pluripotent	Can form almost any cell type (not placenta); used in research and therapy.
Multipotent	Can form a limited range of cell types (e.g., bone marrow → blood cells).
Unipotent	Can differentiate into one cell type (e.g., cardiomyocytes).

Stem cells and induced pluripotentcy

• Stem cells originate undifferentiated and can specialize via differentiation.

• Potency types: totipotent, pluripotent, multipotent, unipotent.

• Uses: regenerative medicine (skin grafts, beta-cells for diabetes, neurons for Parkinson’s).

• Risks/ethical issues: tumor formation, ethical concerns with embryo destruction.

• Induced pluripotent stem (iPS) cells:

  • Somatic cells reprogrammed using transcription factors to restore pluripotency.

  • Avoid embryo destruction; show self-renewal; potential medical use.

Transcriptional factors

• Transcription occurs when cytoplasmic proteins (transcription factors) enter nucleus and bind promoter.

• Each transcription factor binds specific base sequence due to tertiary structure complementarity.

• Binding stimulates RNA polymerase → transcription → mRNA → translation.

• Example: estrogen (lipid-soluble steroid) diffuses into cytoplasm, binds a transcription factor receptor, changes tertiary structure, activates it to enter nucleus and stimulate transcription.