BIOCHEM 2027 Specialised Subject · 1-4
2027 · High School Specialised Subject · Biochemistry

1-4 The Genetic Foundations

DNA, replication accuracy and the path to protein

DNA as the store of information, replication with high fidelity and continuous repair, and the route from a linear sequence to a three-dimensional protein.

3 SECTIONSOutline notesEnglish edition
01

Genetic continuity is based on DNA information storage and transmission

Genes, chromosomes and genomes are three different levels of the same information.

  • Gene — a segment of DNA whose sequence specifies a functional product (RNA or protein), together with the signals that control its expression
  • Chromosome — the DNA molecule packaged with proteins; prokaryotes usually carry one circular chromosome, eukaryotes several linear ones
  • Genome — the complete DNA content of a cell or organism, including coding and non-coding regions
  • Base pairing — A–T and G–C pairs hold two antiparallel strands together, so one strand templates the other
  • Antiparallel — one strand runs 5′→3′ while its partner runs 3′→5′
  • Implication — the sequence is copied with high fidelity and can be repaired, which is what makes heredity stable
Figure 1-40Genetic variation and its transmission through replication
Table 1.4-1Nucleotide, gene, chromosome, genome and plasmid
Table 1.4-6Model predictions compared with observation
Table 1.4-9Key terms summarised in one sentence
Table 1.4-10The standard genetic code
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01

Genetic continuity is based on DNA information storage and transmission

Genes, chromosomes and genomes are three different levels of the same information.

  • Gene — a segment of DNA whose sequence specifies a functional product (RNA or protein), together with the signals that control its expression
  • Chromosome — the DNA molecule packaged with proteins; prokaryotes usually carry one circular chromosome, eukaryotes several linear ones
  • Genome — the complete DNA content of a cell or organism, including coding and non-coding regions
  • Base pairing — A–T and G–C pairs hold two antiparallel strands together, so one strand templates the other
  • Antiparallel — one strand runs 5′→3′ while its partner runs 3′→5′
  • Implication — the sequence is copied with high fidelity and can be repaired, which is what makes heredity stable
Figure 1-40Genetic variation and its transmission through replication
02

DNA is replicated with high accuracy and continuously repaired

Complementary base pairing alone is not accurate enough; proofreading and repair add several orders of magnitude.

  • Semiconservative replication — each daughter molecule keeps one parental strand and one new strand
  • Meselson–Stahl — one intermediate band in the first generation, intermediate plus light bands in the second, distinguishes semiconservative from conservative copying
  • Direction — DNA polymerase adds dNTPs to the 3′-OH end, so the new strand grows 5′→3′ while the template is read 3′→5′
  • Leading and lagging strands — continuous synthesis on one side, Okazaki fragments on the other
  • Machinery — helicase unwinds, primase lays RNA primers, polymerase extends, ligase seals nicks
  • Proofreading — the 3′→5′ exonuclease activity of many replicative polymerases removes misincorporated bases
  • Mismatch repair — corrects errors that survive replication
  • Error rate — textbooks quote roughly one error per 10⁹–10¹⁰ bases after proofreading and repair; observed mutation rates vary with organism and conditions
  • Damage ≠ replication error — damage is chemical alteration of DNA; a replication error is a wrong base in the new strand. Unrepaired damage can become a permanent mutation
  • Repair routes — base excision repair, nucleotide excision repair (UV photoproducts), mismatch repair, homologous recombination and non-homologous end joining for double-strand breaks
  • Expected errors — E = Np; for N = 4.0 × 10⁶ and p = 1.0 × 10⁻⁹, E = 4.0 × 10⁻³ and P(≥1) ≈ 0.40 %
New strand: 5′ → 3′  ·  template read: 3′ → 5′
E = Np  ·  P(≥1) ≈ 1 − e−Np
NOTERepair is not always perfect restoration. Depending on the pathway chosen, repair can leave small insertions, deletions or rearrangements.
Figure 1-45Three stages that raise replication accuracy
Table 1.4-2Meselson–Stahl density bands: expected proportions
Table 1.4-4DNA damage and replication errors: causes and responses
Table 1.4-3Components of the replication machinery
03

Linear DNA sequence leads to three-dimensional protein structure and function

DNA → RNA → protein is the main flow, but it is not the only flow and not a complete description of function.

  • Transcription — RNA polymerase reads the template strand 3′→5′ and synthesises RNA 5′→3′; RNA uses ribose and uracil
  • Example — coding 5′-ATG GAA TTT TGA-3′ → mRNA 5′-AUG GAA UUU UGA-3′
  • Processing — eukaryotic pre-mRNA acquires a 5′ cap, spliced exons and a poly(A) tail; alternative splicing yields different products from one gene
  • Genetic code — 4³ = 64 codons; 61 specify amino acids, UAA/UAG/UGA terminate, AUG starts and codes methionine
  • Translation — tRNA anticodons read codons; aminoacyl-tRNA synthetases charge tRNAs; the ribosome catalyses peptide bond formation in its rRNA
  • Example — AUG GAA UUU UGA gives Met–Glu–Phe; the stop codon is a signal, not a residue
  • Structure levels — primary sequence, secondary α-helix/β-sheet, tertiary folding of one chain, quaternary assembly of several chains
  • Sequence is necessary, not sufficient — pH, ionic strength, temperature, redox state, ligands and chaperones all shape the actual structure
  • Mutation outcomes — synonymous, missense, nonsense and frameshift changes; sickle-cell β-globin Glu→Val shows one substitution altering molecular behaviour
  • Expression matters — cells with near-identical genomes differ in which genes they express, at which level, and in what quantity
Figure 1-48Substitution and deletion changing the translated sequence
Table 1.4-5Four levels of protein structure
Table 1.4-7Expected errors by error probability
Table 1.4-8Effect of a substitution and a single-base deletion
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03

Linear DNA sequence leads to three-dimensional protein structure and function

DNA → RNA → protein is the main flow, but it is not the only flow and not a complete description of function.

  • Transcription — RNA polymerase reads the template strand 3′→5′ and synthesises RNA 5′→3′; RNA uses ribose and uracil
  • Example — coding 5′-ATG GAA TTT TGA-3′ → mRNA 5′-AUG GAA UUU UGA-3′
  • Processing — eukaryotic pre-mRNA acquires a 5′ cap, spliced exons and a poly(A) tail; alternative splicing yields different products from one gene
  • Genetic code — 4³ = 64 codons; 61 specify amino acids, UAA/UAG/UGA terminate, AUG starts and codes methionine
  • Translation — tRNA anticodons read codons; aminoacyl-tRNA synthetases charge tRNAs; the ribosome catalyses peptide bond formation in its rRNA
  • Example — AUG GAA UUU UGA gives Met–Glu–Phe; the stop codon is a signal, not a residue
  • Structure levels — primary sequence, secondary α-helix/β-sheet, tertiary folding of one chain, quaternary assembly of several chains
  • Sequence is necessary, not sufficient — pH, ionic strength, temperature, redox state, ligands and chaperones all shape the actual structure
  • Mutation outcomes — synonymous, missense, nonsense and frameshift changes; sickle-cell β-globin Glu→Val shows one substitution altering molecular behaviour
  • Expression matters — cells with near-identical genomes differ in which genes they express, at which level, and in what quantity
Figure 1-48Substitution and deletion changing the translated sequence
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