Translation, Gene Regulation & Mutations

Translation

• $mRNA$ read in $3$-base codons → $1$ amino acid each
• Universal start codon $AUG$ → methionine; preceded by untranslated leader sequence (guides ribosome, not translated)
• Ribosome sites: A (arrival), P (peptide-bond), E (exit)
• tRNA: anticodon complementary to codon; carries specific amino acid
• Elongation: shift $3$ bases → transfer peptide from P-site tRNA to A-site amino acid → empty tRNA exits E-site
• Stop codons ($UAA, UAG, UGA$) load no amino acid → chain released, folds into protein

Genetic Code & Redundancy

• $4$ bases → $4^3 = 64$ codons, $20$ amino acids
• Degenerate: multiple codons for same amino acid (mostly vary at 3rd base → “wobble”)
• 2nd base most conserved; changes usually alter amino acid
• Code is universal → basis for genetic engineering (e.g., bacterial insulin)

Gene Expression: Prokaryotes vs. Eukaryotes

• Prokaryotes: polycistronic mRNA, transcription & translation occur simultaneously (no nucleus)
• Eukaryotes: monocistronic mRNA; transcription in nucleus, post-transcriptional modification (splicing, editing) before export

Gene Regulation Levels

1. DNA accessibility (supercoiling/histones)
2. Transcriptional control (promoters; operons in prokaryotes)
3. Post-transcriptional modification (eukaryotes only)
4. Translational control (ribosome activity; antibiotic targets)
5. Post-translational modification (cofactors, folding)
6. Protein degradation (last-resort energy waste)

Operons

Inducible (e.g., lac)

• Default OFF: repressor bound to operator
• Inducer (lactose) binds repressor → repressor leaves DNA → transcription of catabolic genes proceeds

Repressible (e.g., trp)

• Default ON: repressor inactive
• Corepressor (tryptophan) activates repressor → binds operator → transcription stops; limits anabolic pathways

Mutation Types

• Point mutation (single base)
  • Silent: no amino-acid change
  • Missense: wrong amino acid; effect variable
  • Nonsense: creates stop codon → truncated protein
• Insertion/Deletion (±1 base) → frameshift; usually nonfunctional protein

Mutagens

Chemical

• Base modifiers (e.g., alkylating agents like ethylene oxide) → mispairing without replication
• Base analogs (e.g., 2-aminopurine) incorporated during replication → mispairing
• Intercalating agents (e.g., methylene blue) insert between bases → frameshifts

Radiation

• UV (non-ionizing): forms thymine dimers; repairable by photolyase + visible light
  • $UVA$ deepest penetration (skin cancer), $UVB$ aging, $UVC$ superficial (sunburn)
• Ionizing (X, γ): single & double-strand breaks; used industrially for sterilization

Evolution & Selection

• Mutations exist before environmental change; pressure selects advantageous mutants
• Example: antibiotic-resistant bacteria become dominant only under drug pressure; revert when pressure removed

Cancer-Related Genetics

• Requires multiple mutations; common early pair:
  1. Proliferation gene ON (oncogene)
  2. Apoptosis gene OFF (tumor-suppressor loss)
• Additional hallmarks: cellular immortality, loss of contact inhibition, angiogenesis, metastasis
• Key genes:
  • Oncogenes: $MYC$ (≈$70\%$ cancers), $RAS$ (≈$60\%$ pancreatic)
  • Tumor-suppressors: $p53$ (≈$50\%$ cancers), $BRCA1/2$ (hereditary breast/ovarian risk)
• Genetic screening (e.g., $BRCA$ tests) enables early surveillance or prophylactic measures