Topic 2: Genes and Health — Edexcel A-Level Biology A (Salters-Nuffield)

Gas exchange surfaces must allow sufficient diffusion of O₂ and CO₂ to meet metabolic demands. Three key properties enhance diffusion: a large surface area to volume ratio (SA:V), a thin diffusion pathway, and a maintained concentration gradient. Fick’s Law quantifies the rate: rate of diffusion ∝ (surface area × concentration difference) ÷ thickness. For example, if area doubles while thickness and concentration difference remain constant, the rate doubles. In the mammalian lung, millions of alveoli provide a huge surface area (about 70 m² in humans), their walls are one cell thick, and a rich capillary network plus ventilation and blood flow maintain steep gradients. These features together enable rapid gaseous exchange.

Cell membranes are phospholipid bilayers with embedded proteins, cholesterol, glycoproteins and glycolipids. The hydrophilic phosphate heads face outward, and hydrophobic fatty acid tails face inward, forming a barrier to water-soluble substances. Proteins act as channels, carriers, receptors and enzymes. Cholesterol regulates fluidity. The fluid mosaic model describes membranes as a fluid phospholipid bilayer with a mosaic of proteins and other components that can move laterally. This model is an interpretation of data from techniques such as electron microscopy, freeze-fracture, and fluorescent antibody tagging, which showed that proteins are dispersed in the bilayer and can move. The model explains properties such as selective permeability, cell signalling, and cell adhesion.

Osmosis is the net movement of free water molecules through a partially permeable membrane from a region of higher water concentration to a region of lower water concentration. Free water molecules are those not bound to solutes, so adding solute reduces their concentration. The membrane allows small water molecules through but restricts larger solute particles, so water moves down its concentration gradient. This movement is passive and continues until the concentrations equalise or the membrane is opposed by an external pressure. In cells, osmosis explains turgor in plant cells and lysis or shrinkage in animal cells. Water potential is not required here; describe the gradient simply as higher or lower water concentration.

Passive transport moves substances down a concentration gradient without metabolic energy. Simple diffusion occurs directly through the phospholipid bilayer for small non-polar molecules such as O₂ and CO₂. Facilitated diffusion uses channel proteins for ions or carrier proteins for polar molecules such as glucose, still down the gradient. Active transport uses carrier proteins to move substances against the gradient, powered by ATP hydrolysed to ADP and Pi, which is the immediate energy source. Endocytosis engulfs material in a vesicle formed from the membrane; exocytosis fuses a vesicle with the membrane to release contents. Carrier proteins change shape to move specific solutes; channel proteins form hydrophilic pores. Both are integral membrane proteins and show specificity.

A mononucleotide has a pentose sugar, a phosphate group and a nitrogenous base. DNA contains deoxyribose and the bases adenine, thymine, cytosine and guanine; RNA contains ribose and uracil replaces thymine. Mononucleotides join by condensation reactions between the phosphate of one and the sugar of the next, forming phosphodiester bonds and releasing water, producing polynucleotides. DNA is two antiparallel polynucleotide strands; RNA is usually single-stranded. Complementary base pairing occurs between adenine and thymine (or uracil in RNA) and between cytosine and guanine. Hydrogen bonds between these complementary bases hold the two DNA strands together, and the strands twist into a double helix.

Protein synthesis begins with transcription in the nucleus. RNA polymerase binds to the DNA template (antisense) strand and moves along it, unwinding the double helix and linking complementary RNA nucleotides into a messenger RNA (mRNA) molecule. The mRNA strand is complementary to the template strand and identical in sequence to the coding (sense) strand, except that uracil replaces thymine. The mRNA then leaves the nucleus and attaches to a ribosome in the cytoplasm. During translation, the ribosome reads each codon on the mRNA. Transfer RNA (tRNA) molecules carry specific amino acids and have anticodons that are complementary to the mRNA codons. The ribosome catalyses the formation of peptide bonds between adjacent amino acids. Translation starts at a start codon and ends at a stop codon, which does not code for an amino acid and releases the completed polypeptide.

The genetic code is the set of rules by which the sequence of bases in DNA and mRNA is translated into the sequence of amino acids in a polypeptide. It is a triplet code: every three bases (a codon) on mRNA specifies one amino acid. The code is non-overlapping, meaning each base is read only once and belongs to only one codon; the reading frame is set by the start codon. The code is also degenerate: most amino acids are encoded by more than one codon, although each codon specifies only one amino acid. For example, the amino acid leucine is coded by six different codons. These features allow the code to tolerate some mutations without changing the amino acid sequence, and they ensure that the sequence of bases is read accurately during translation.

A gene is a length of DNA whose base sequence carries information. DNA is a polymer of nucleotides, each with deoxyribose, a phosphate group and one of four bases: A, T, C or G. Along one strand, bases occur in a definite order, and this order is the genetic code. During protein synthesis the DNA sequence is transcribed into messenger RNA, then translated at a ribosome. Each set of three bases, a triplet or codon, specifies one amino acid, so the linear order of bases dictates the linear order of amino acids. Those amino acids join by peptide bonds to form a polypeptide chain, which folds to give a protein. Thus a gene codes for the sequence of amino acids in a polypeptide chain, and the polypeptide's sequence determines its properties.

An amino acid has a central carbon bonded to an amino group, a carboxyl group, a hydrogen atom and a variable R group. Amino acids are monomers that join by condensation, the carboxyl group of one reacting with the amino group of the next to form a peptide bond and release water, giving a polypeptide. The primary structure is the order of amino acids, determining folding and properties. Hydrogen bonds, ionic bonds, disulfide bridges and hydrophobic interactions stabilise the three-dimensional shape. Globular proteins like haemoglobin are compact and soluble; haemoglobin has a quaternary structure of four polypeptide chains, each with an oxygen-binding haem group. Fibrous proteins like collagen form long, insoluble chains; collagen consists of three polypeptide chains wound in a triple helix with high glycine content, cross-linked for tensile strength.

Enzymes are globular proteins whose precise three-dimensional conformation creates an active site complementary to a specific substrate. Substrate binding forms an enzyme–substrate complex; strain and orientation effects lower the activation energy, so the reaction proceeds faster without changing the equilibrium position. Specificity arises because only substrates with a complementary shape and chemistry can bind; a different substrate cannot form a stable complex. Intracellular enzymes, such as those in the cytosol or mitochondria, catalyse reactions inside cells. Extracellular enzymes, such as digestive amylase or protease, are synthesised inside cells and secreted to act outside, often in the gut lumen. Denaturation, for example by high temperature or extreme pH, disrupts the active site and abolishes catalytic activity.

DNA replication is semi-conservative: the double helix unwinds, hydrogen bonds between complementary bases break, and each parental strand acts as a template. Free DNA nucleotides align by complementary base pairing (A with T, C with G). DNA polymerase catalyses phosphodiester bond formation between the 3′‑OH of one nucleotide and the 5′‑phosphate of the next, extending the new strand 5′→3′. Meselson and Stahl grew E. coli in ¹⁵N medium, then transferred cells to ¹⁴N medium. After one generation, all DNA was hybrid (intermediate density); after two, half was hybrid and half light. This supported semi-conservative replication and refuted conservative and dispersive theories.

Errors during DNA replication, such as base substitution, insertion or deletion, can change the nucleotide sequence. A substitution may alter one codon and hence one amino acid, while insertions or deletions can shift the reading frame, altering many amino acids and often producing a non-functional protein. Cystic fibrosis results from mutations in the CFTR gene, which encodes a chloride ion channel. Many different mutations can cause the disease, including the common deletion of three nucleotides that removes phenylalanine at position 508 (F508del). This misfolds the protein, so it is degraded before reaching the membrane, reducing chloride transport and leading to thick mucus in the lungs and pancreas.

A gene is a DNA base sequence coding for a polypeptide; an allele is one version of that gene. Genotype is the alleles present; phenotype is the observable characteristic, shaped by genotype and environment. A dominant allele shows its effect when present; a recessive allele shows only when two copies are present. In incomplete dominance the heterozygote shows an intermediate phenotype. A homozygote carries identical alleles; a heterozygote carries different alleles. Monohybrid inheritance tracks one gene: construct a Punnett square from parental gametes, then state offspring ratios. Pedigree diagrams use symbols for males, females and affected individuals; assign genotypes from affected offspring, then deduce carriers and probabilities.

Cystic fibrosis results from a mutation in the CFTR gene, so the CFTR chloride channel is faulty. Chloride ions are not transported normally, so water movement changes and mucus becomes abnormally thick and sticky. In the gaseous exchange system, this mucus obstructs airways and bronchioles, increasing infection risk and reducing gas exchange. In the digestive system, blocked pancreatic ducts prevent digestive enzymes reaching the small intestine, so food is poorly digested and nutrients are absorbed less efficiently. In the reproductive system, thickened mucus blocks the cervix and sperm ducts, reducing fertility; in males the vas deferens may be absent.

Genetic screening tests DNA or chromosomes to find a specific allele or karyotype. Carrier identification tests adults with a family history, e.g. a blood sample for the cystic fibrosis allele, so couples learn the chance of an affected child. PGD screens embryos created by IVF before implantation: a cell is removed at about the 8-cell stage and tested, and unaffected embryos are transferred. Prenatal testing screens a fetus. Amniocentesis samples amniotic fluid with a needle at about 15–20 weeks; chorionic villus sampling (CVS) takes chorionic villi at about 11–14 weeks. CVS gives earlier results but carries a slightly higher miscarriage risk. Implications include false results, procedure-related miscarriage, and decisions about continuing or ending a pregnancy.

Genetic screening raises social and ethical issues that can be examined from several viewpoints. A consequentialist or utilitarian view weighs the benefits of avoiding suffering against the harms of miscarriage, false results and termination. A rights-based view asks whether the fetus or embryo has rights, and whether parents have a right to information and to choose. A religious view may hold that life begins at conception, opposing embryo destruction in PGD. Social issues include insurance and employment discrimination, stigma, disability rights, cost and unequal access, and pressure on parents to test or to terminate. Discussing means presenting more than one viewpoint, using evidence, and reaching a reasoned judgement rather than asserting one opinion.

This core practical links the fluid-mosaic model to measurable permeability. Beetroot tissue is cut into equal cylinders, rinsed to remove pigment from cut cells, then placed in a water bath at a set temperature or in a series of alcohol concentrations. The pigment betalain leaks from damaged membranes into the surrounding solution; its absorbance is read in a colorimeter, or the depth of colour is compared against a colour standard. As temperature rises, phospholipids gain kinetic energy and the bilayer becomes more fluid, while proteins may denature; above roughly 60 °C leakage rises steeply. Alcohol dissolves lipids, disrupting the bilayer so permeability increases with concentration. Control variables include cylinder length, surface area, rinse time, volume of solution and time in the bath.

In this core practical you measure how changing enzyme concentration or substrate concentration affects the initial rate of an enzyme-catalysed reaction. Initial rate is the rate at the very start, when substrate concentration is known and product inhibition is negligible. A common method uses catalase and hydrogen peroxide: mix a fixed volume of buffered substrate with enzyme, then measure the volume of oxygen produced over time using a gas syringe or inverted burette. Alternatively, use a colorimeter to follow the disappearance of a coloured substrate or the appearance of a coloured product. Plot volume or absorbance against time, draw a tangent at time zero, and calculate the gradient to obtain the initial rate. Control temperature, pH and enzyme or substrate volume so that only the independent variable changes.