1-4 The Genetic Foundations

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

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 %

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

Data tables for this section, shown on click and printed in the appendix.