Gene expression and inheritance

What the exam asks

Expect a pedigree, a cross with a ratio attached, or an operon with one component mutated. The pedigree items are the ones worth drilling, because they are pure method: you are given a family and four candidate modes of inheritance, and the fastest route is elimination rather than working out genotypes. Two observations do most of the work. An affected child of unaffected parents means recessive, and an affected daughter whose father is unaffected means not X-linked recessive. Run those in order and the answer usually falls out before you have written anything down. The trap with the ratios is treating 9:3:3:1 as what two genes do, rather than as what two independent, non-interacting genes do. When a cross gives 9:3:4 or 9:7, candidates hunt for an arithmetic slip; the ratio is the answer, and it is telling you the genes interact. Sum the classes: if they still total sixteen, nothing was lost, they were merged.

Two halves that the exam treats as one. Regulation is about which genes a cell is reading right now and what makes it change its mind. Inheritance is about which alleles get passed on and in what proportions. Both are examined as prediction: you are given a system and asked what it does when something is altered.

Regulation is best carried in as a switch with parts, not as a story. In a bacterial operon there is a regulatory gene making a repressor, an operator the repressor sits on, a promoter, and the structural genes. Break any one part and you can predict the result without recalling the operon at all. Break the repressor or the operator and the genes come on and stay on. Break a structural gene and transcription is normal but the enzyme does not work. The lac operon is inducible because its substrate switches it on; the trp operon is repressible because its product switches it off. That is the whole difference, and it follows from one being a pathway that breaks something down and the other a pathway that builds something.

Inheritance is arithmetic with a rule about when the arithmetic applies. The 9:3:3:1 of a dihybrid cross is not a fact about two genes, it is a fact about two genes that assort independently and act independently. Linkage breaks the first assumption and epistasis breaks the second, and the exam signals both by handing you a ratio that is nearly 9:3:3:1 but not quite.

Pedigrees deserve separate practice, because they are not recall at all. They are elimination, run in a fixed order, and the order is what makes them fast.

What to hold

• An affected child born to two unaffected parents shows the trait is recessive, because both parents must have carried an allele they do not show.
• An unaffected child born to two affected parents shows the trait is dominant, by the same argument run the other way.
• A father passes his X to every daughter and to no son, so an affected daughter with an unaffected father rules out X-linked recessive inheritance.
• No father-to-son transmission of a trait is expected under X linkage, because a son receives his father's Y and not his X.
• A test cross against a homozygous recessive reveals an unknown genotype directly: all dominant offspring indicates homozygous, a 1:1 split indicates heterozygous.
• A dihybrid self-cross gives 9:3:3:1 only when the two genes are unlinked and neither interferes with the other's expression.
• Linked genes are detected in a test cross by an excess of parental combinations over recombinant ones, where 1:1:1:1 was expected.
• Recombination frequency, as recombinants over total offspring, estimates map distance in centimorgans and cannot usefully exceed 50%, which is what unlinked genes already give.
• Epistasis is one gene masking another's phenotype, and it shows up as a 9:3:3:1 ratio collapsed into fewer classes, such as 9:3:4 or 9:7.
• In the lac operon, lactose removes the repressor from the operator, but high glucose keeps cAMP low so the activator does not bind and expression stays modest.
• In the trp operon, tryptophan acts as a corepressor: it activates the repressor, so the pathway that makes tryptophan is shut off when tryptophan is already present.
• In eukaryotes, histone acetylation loosens chromatin and is associated with active transcription, while DNA methylation of a promoter is associated with silencing.