(a)(i) Describe composition of plasma membrane. (10 marks) (a)(ii) Differentiate between facilitated and passive diffusion across…

(a)

(i) Composition of the plasma membrane

The plasma membrane is about 7.5–10 nm thick and is described by the fluid mosaic model of Singer and Nicolson (1972): a fluid lipid bilayer in which proteins float like icebergs. By weight it is roughly 40–50% lipid, 40–55% protein and 2–10% carbohydrate; the ratio varies with function (myelin is about 80% lipid, the inner mitochondrial membrane about 75% protein).

• Phospholipids: amphipathic molecules with a polar head (phosphate plus choline, ethanolamine, serine or inositol) and two fatty-acid tails. They form a bilayer with heads facing the water and tails inside. The main ones are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and sphingomyelin. The two leaflets differ (asymmetry): phosphatidylcholine and sphingomyelin are mainly outside, phosphatidylserine and phosphatidylethanolamine inside, and exposure of phosphatidylserine outside marks apoptotic cells. Unsaturated (kinked) tails increase fluidity.
• Cholesterol: up to about one molecule per phospholipid in animal cells; it buffers fluidity, reduces permeability and, with sphingolipids, forms lipid rafts.
• Glycolipids: sugar-bearing lipids (cerebrosides, gangliosides) on the outer leaflet only.
• Proteins: integral (transmembrane) proteins span the bilayer, usually by α-helices of hydrophobic amino acids, and act as channels, carriers, pumps and receptors; peripheral proteins bind loosely to the surfaces or to integral proteins (e.g., spectrin under the red-cell membrane); lipid-anchored proteins are tethered by covalent lipids (e.g., GPI anchors). Proteins can move laterally but rarely flip across.
• Carbohydrates: short oligosaccharide chains on glycoproteins and glycolipids form the glycocalyx on the outer surface, used for cell recognition, adhesion and blood-group antigens (ABO).

The membrane is selectively permeable: small non-polar molecules cross the lipid directly, while ions and polar molecules need proteins.

(ii) Passive (simple) and facilitated diffusion

Both are forms of passive transport: substances move down their concentration (or electrochemical) gradient and no metabolic energy (ATP) is used, which distinguishes both from active transport. They differ as follows.

• Simple diffusion: molecules pass directly through the lipid bilayer without a membrane protein. It is used by small, non-polar or lipid-soluble molecules such as O₂, CO₂, N₂, steroid hormones, ethanol and urea (slowly). The rate is proportional to the concentration gradient and lipid solubility (Fick's law), is not saturable, shows no specificity, and is not inhibited by specific inhibitors.
• Facilitated diffusion: movement requires a specific membrane protein, a channel or a carrier. Channels form water-filled pores, often gated, for ions and water, such as voltage-gated Na⁺ and K⁺ channels and aquaporins (AQP2 in kidney collecting ducts). Carriers (uniporters) bind the solute and change shape to release it on the other side, such as GLUT1 carrying glucose into red cells and GLUT4 in muscle and fat (moved to the membrane by insulin). It is specific (GLUT1 carries D-glucose but not L-glucose), shows saturation kinetics (a maximum rate Vmax when all carriers are occupied, and a Km), can be inhibited competitively (e.g., by cytochalasin B for GLUT1), and is much faster than simple diffusion for polar solutes.

On a graph of rate against concentration, simple diffusion is a straight line, while facilitated diffusion is a hyperbola levelling off at Vmax.

(b) How mutations affect variation in populations and natural selection

A mutation is a heritable change in DNA and the ultimate source of new alleles; recombination only reshuffles existing variation.

• Kinds: point mutations (base substitutions, either transitions or transversions, which may be silent, missense or nonsense) and frameshifts from insertions or deletions not in multiples of three; chromosomal mutations (deletions, duplications, inversions, translocations); and genome mutations (aneuploidy, polyploidy). Gene duplications are especially important, as copies can acquire new functions (e.g., the globin gene family).
• Origin and rate: they arise from replication errors, spontaneous chemical changes and mutagens (UV, ionising radiation, chemicals). Rates are low, about 10⁻⁵ to 10⁻⁶ per gene per generation, but in large populations over many generations they supply abundant variation; each human carries roughly 60–70 new mutations.
• Effects on fitness: most mutations are neutral or slightly harmful, some are strongly harmful and a few are beneficial in a particular environment. Their effect depends on the environment: the sickle-cell allele (HbS) is harmful in homozygotes but protects heterozygotes against falciparum malaria.
• Effect on population variation: mutation alone changes allele frequencies very slowly and is one of the forces that disturb Hardy–Weinberg equilibrium (p² + 2pq + q² = 1), together with selection, genetic drift, migration and non-random mating. New mutations enter the gene pool as rare alleles; in small populations their fate is largely decided by drift, and many neutral mutations are fixed by drift (Kimura's neutral theory), which forms the basis of the molecular clock.
• Interaction with natural selection: selection acts on phenotypes produced by these variants, increasing alleles that raise survival and reproduction and removing harmful ones (purifying selection), so that a balance between mutation and selection keeps harmful recessive alleles at low frequency. Selection can be directional, stabilising, disruptive or balancing (heterozygote advantage, as with HbS).
• Examples: antibiotic resistance in bacteria (e.g., rpoB mutations giving rifampicin resistance in Mycobacterium tuberculosis); insecticide resistance in mosquitoes (kdr mutations in the sodium-channel gene); industrial melanism in the peppered moth Biston betularia, where a transposon insertion in the cortex gene produced the dark form that increased in soot-darkened areas; and lactase persistence in pastoral human populations.

(c) Pedigrees for autosomal recessive and sex-linked inheritance in humans

Conventions: squares are males and circles females; filled symbols are affected; half-filled symbols (autosomal) or a dot in the centre (X-linked) show carriers; a horizontal line joins mates, and a double line shows a consanguineous marriage; offspring hang from a vertical line; generations are numbered with Roman numerals and individuals with Arabic numerals.

Autosomal recessive (β-thalassaemia, gene HBB on chromosome 11; also sickle-cell disease, albinism):

• Generation I: I-1 (half-filled square) and I-2 (half-filled circle) are first cousins, joined by a double line; both are unaffected carriers (Aa).
• Generation II: their children are II-1 (filled circle, affected daughter, aa), II-2 (filled square, affected son), II-3 (half-filled circle, carrier) and II-4 (open square, normal).
• Generation III: II-2 marries an unrelated non-carrier woman (open circle); their children III-1 and III-2 are all unaffected carriers (half-filled).

Features: affected children usually have unaffected carrier parents; both sexes are affected equally; about one in four children of two carriers is affected; the trait skips generations; and consanguinity raises the risk.

X-linked recessive (haemophilia A, factor VIII gene F8 on Xq28; also colour blindness, Duchenne muscular dystrophy):

• Generation I: I-1 (filled square, affected man, XʰY) marries I-2 (open circle, normal).
• Generation II: all their daughters are carriers (II-1, circle with a central dot, XᴴXʰ) and all sons normal (II-2, open square), since a father gives his X only to daughters.
• Generation III: II-1 marries a normal man (open square); their children are III-1 (filled square, affected son), III-2 (open square, normal son), III-3 (circle with dot, carrier daughter) and III-4 (open circle, normal daughter), in an expected 1:1 ratio among sons and among daughters.

Features: mostly males are affected; the trait passes from an affected man through his carrier daughter to half of her sons (criss-cross inheritance, skipping a generation); there is no male-to-male transmission; affected females are rare (affected father and carrier mother). The haemophilia of Queen Victoria's descendants in the European royal families is the classic human example.