Gene Control
Every cell in an organism carries the same genome — yet cells differentiate because different genes are expressed. Gene control examines how structural and regulatory genes, the lac operon, transcription factors, and hormone-mediated derepression (gibberellin/DELLA) determine which proteins are made, when, and where.
Gene → Protein → Phenotype
A gene is a sequence of DNA that codes for a polypeptide (or functional RNA). The polypeptide carries out a function that contributes to the organism's phenotype. Mutations that alter the gene sequence can produce a non-functional protein, changing the phenotype.
Named gene examples — official 9700 requirements
| Gene | Protein coded for | Normal function | Mutant phenotype |
|---|---|---|---|
| TYR | Tyrosinase enzyme | Catalyses conversion of tyrosine → melanin (pigment synthesis) | Mutation → non-functional tyrosinase → no melanin produced → albinism |
| HBB | β-globin polypeptide (part of haemoglobin) | Oxygen transport in red blood cells; haemoglobin binds O₂ | Single base substitution (GAG→GTG) → valine replaces glutamate at position 6 → sickle cell haemoglobin (HbS) → sickling in low O₂ |
| F8 | Clotting factor VIII | Essential for the blood clotting cascade (intrinsic pathway); activates factor X | Mutation → non-functional factor VIII → blood cannot clot normally → haemophilia A |
| HTT | Huntingtin protein | Normal function not fully understood; involved in neuronal survival | CAG trinucleotide repeat expansion (>36 repeats) → mutant huntingtin → neuronal death → Huntington’s disease (progressive neurodegeneration) |
| Le | Enzyme in gibberellin synthesis pathway | Catalyses a step in GA biosynthesis → normal GA levels → stem elongation | le allele → non-functional enzyme → low GA → dwarf phenotype in peas |
For each example, know: (1) the gene name, (2) the protein product, (3) the protein's normal role, (4) how the mutation changes the protein, (5) the resulting phenotype change. The TYR/albinism and HBB/sickle cell examples are most commonly asked in detail.
Albinism is caused by a mutation in the TYR gene. Explain how this mutation results in the albino phenotype. [4]
- The TYR gene normally codes for the enzyme tyrosinase [1]
- The mutation alters the base sequence of TYR, resulting in a change in the amino acid sequence of tyrosinase [1]
- The altered tertiary structure of tyrosinase means it cannot bind its substrate (tyrosine) or catalyse the conversion of tyrosine to melanin [1]
- Without melanin (pigment), the skin, hair, and eyes lack normal colouration — the albino phenotype [1]
Structural Genes, Regulatory Genes, and Enzyme Induction
A gene that codes for a protein used directly in the cell's structure or metabolism — e.g. an enzyme, structural protein, or transport protein.
Example: the lacZ gene in the lac operon codes for β-galactosidase (the enzyme that cleaves lactose).
A gene that codes for a regulatory protein that controls the expression of other genes. The regulatory protein may activate or repress transcription of structural genes.
Example: the lacI gene codes for the lac repressor protein, which controls whether the lac operon structural genes are transcribed.
Inducible and repressible enzymes
| Type | Definition | Default state | Trigger | Example |
|---|---|---|---|---|
| Inducible enzyme | Not synthesised unless an inducer (often the substrate) is present; enzyme is “switched on” by the substrate | OFF (repressed) | Substrate (inducer) binds repressor → repressor leaves operator → genes expressed | β-galactosidase (lac operon) — only made when lactose is present |
| Repressible enzyme | Normally synthesised; a corepressor (often the product) switches it off when the product accumulates | ON (expressed) | Product (corepressor) binds aporepressor → complex blocks operator → genes repressed | Tryptophan biosynthesis enzymes — repressed when tryptophan accumulates (trp operon) |
Inducible and repressible systems allow bacteria to be metabolically efficient: they only produce enzymes when needed. Making β-galactosidase all the time would waste amino acids; making it only when lactose is present is economical. This is one of the core insights from the Jacob and Monod lac operon work.
The Lac Operon
The lac operon is a classic example of prokaryotic gene regulation. It controls the production of β-galactosidase and other proteins needed for lactose metabolism in Escherichia coli. It demonstrates negative control (repressor protein switches genes off) and enzyme induction.
| Component | Function |
|---|---|
| lacI gene (regulatory gene) | Codes for the lac repressor protein; constitutively expressed (always transcribed) |
| Promoter (P) | Binding site for RNA polymerase; transcription starts here |
| Operator (O) | DNA sequence where repressor protein binds; blocks RNA polymerase progress when occupied |
| lacZ (structural gene) | Codes for β-galactosidase — cleaves lactose → glucose + galactose |
| lacY (structural gene) | Codes for lactose permease — membrane transport protein that brings lactose into the cell |
| lacA (structural gene) | Codes for thiogalactoside transacetylase (role less important for 9700) |
Lac operon: lactose ABSENT
- The lacI regulatory gene is continuously transcribed and translated, producing lac repressor protein
- The repressor protein has two binding sites: one for the operator DNA, one for the inducer (lactose)
- When lactose is absent, the repressor protein binds to the operator region of the operon
- The bound repressor physically blocks RNA polymerase from progressing past the operator → structural genes (lacZ, lacY, lacA) are not transcribed
- No β-galactosidase or lactose permease is produced — energy and resources are saved
Lac operon: lactose PRESENT
- Lactose enters the cell (via a small amount of pre-existing permease); intracellular lactose is converted to allolactose (the actual inducer)
- Allolactose binds to the second binding site on the lac repressor protein
- Binding causes a conformational change in the repressor — the repressor can no longer bind the operator DNA
- The repressor dissociates from the operator
- RNA polymerase can now bind the promoter and transcribe the structural genes (lacZ, lacY, lacA) as a single mRNA (polycistronic mRNA)
- Translation produces β-galactosidase and lactose permease → lactose is metabolised
- When all lactose is consumed, no more allolactose is present → repressor reassumes its active shape → rebinds operator → genes switched off again
The lac operon uses negative control: the repressor protein is the controlling element, and it acts to prevent transcription when it is active. The system is “on by default” when the repressor is inactivated. This contrasts with positive control (where an activator protein is needed to switch genes on). The lac operon also has a positive control component (CAP/cAMP for glucose sensing) but this is NOT required for 9700.
Describe what happens in an E. coli cell when lactose is added to a glucose-free medium. Refer to the lac operon components in your answer. [6]
- Lactose is converted to allolactose (the inducer) inside the cell [1]
- Allolactose binds to the lac repressor protein, causing a conformational change [1]
- The repressor can no longer bind to the operator; it dissociates from the operator sequence [1]
- RNA polymerase binds to the promoter and transcribes the structural genes lacZ, lacY (and lacA) [1]
- mRNA is translated → β-galactosidase (cleaves lactose to glucose + galactose) and lactose permease (increases lactose uptake) are produced [1]
- When lactose is depleted, allolactose levels fall; repressor reverts to its active conformation and rebinds the operator, switching off transcription [1]
Transcription Factors in Eukaryotes
In eukaryotes, gene expression is regulated by transcription factors — proteins that bind to specific DNA sequences and control whether RNA polymerase can transcribe a gene.
- Bind to specific regulatory DNA sequences (promoters, enhancers) near the gene they control
- Activator transcription factors: binding promotes RNA polymerase binding and increases transcription rate
- Repressor transcription factors: binding blocks RNA polymerase or prevents activators from working
- Allow the same gene to be switched on or off in different cell types or in response to different signals
Bacteria use operons: one promoter → multiple structural genes, simple on/off control (lac operon). Eukaryotic cells are multicellular and must differentiate; the same genome must produce >200 different cell types. Transcription factors allow fine-grained, combinatorial control: different combinations of TFs are present in different cell types → different subsets of genes are expressed → cell differentiation.
In barley aleurone cells, transcription factors that activate the amylase gene are normally held inactive by DELLA repressor proteins. When gibberellin degrades DELLA proteins, the transcription factors are freed and can bind to the promoter of the amylase gene, initiating transcription. This is a direct example of a transcription factor being controlled by hormone signalling — connecting Topics 15C and 16C.
Gibberellin, DELLA, and Gene Expression Control
The gibberellin/DELLA mechanism is the official 9700 example of hormonal control of gene expression in eukaryotes. It links the plant hormone signal directly to transcriptional regulation — covered in Topic 15C from the plant coordination perspective and here from the gene control perspective.
Without GA: DELLA proteins bind to and inhibit transcription factors → growth/amylase genes are not transcribed → dormancy/dwarf state maintained
With GA: GA binds GID1 receptor → GA-GID1 complex → DELLA protein degraded (ubiquitin-proteasome pathway) → transcription factors freed → bind promoter of target genes (e.g. amylase) → transcription → protein synthesis → physiological response (starch hydrolysis / cell elongation)
| Feature | Lac operon (prokaryote) | DELLA/GA (eukaryote) |
|---|---|---|
| Organism | E. coli (bacterium) | Plants (e.g. barley, peas) |
| Control type | Negative control (repressor blocks transcription) | Derepression (inhibitor of TF removed) |
| Signal molecule | Allolactose (inducer) | Gibberellin (hormone) |
| Gene organisation | Operon (polycistronic mRNA) | Individual eukaryotic genes |
| Response speed | Minutes (direct transcription after repressor removed) | Hours (protein degradation, nuclear signalling) |
In peas, the Le allele codes for a functional enzyme in the GA synthesis pathway. Plants with the Le allele produce normal GA, which degrades DELLA proteins → growth genes expressed → tall. Plants homozygous for le cannot make enough GA → DELLA proteins persist → growth genes suppressed → dwarf.
This is therefore both a gene regulation example (DELLA control of transcription) AND a gene→phenotype example (Le gene → enzyme → GA → phenotype).
Describe how gibberellin controls gene expression in aleurone cells of a germinating barley grain. [5]
- In the absence of gibberellin, DELLA proteins bind to transcription factors, preventing them from activating the amylase gene (and other growth genes) [1]
- Gibberellin from the embryo binds to the GID1 receptor in aleurone cells [1]
- The GA-GID1 complex targets DELLA proteins for degradation (via the ubiquitin-proteasome pathway) [1]
- With DELLA proteins removed, transcription factors are freed and bind to the promoter of the amylase gene [1]
- Transcription of the amylase gene occurs; mRNA is translated to produce α-amylase, which is secreted into the endosperm to hydrolyse starch [1]
Practice Questions
In the lac operon of E. coli, which of the following correctly describes the state of the operon when both lactose and glucose are absent from the medium?
- (A) Repressor is inactive; structural genes are transcribed
- (B) Repressor is active and bound to the operator; structural genes are not transcribed
- (C) Allolactose binds to the promoter and prevents RNA polymerase binding
- (D) Structural genes are constitutively expressed regardless of repressor state
Explain why all cells in an organism contain the same DNA but have different phenotypes. [4]
- All cells in a multicellular organism arise from a single fertilised egg by mitosis, so they inherit the same genome (same DNA sequence) [1]
- Only a subset of genes is expressed in any given cell type; different cell types express different genes [1]
- Transcription factors control which genes are transcribed; different cell types contain different combinations of transcription factors [1]
- The proteins synthesised from expressed genes determine the structure and function of each cell type → different phenotypes despite identical genotypes [1]
Common Mistakes
- ⚔Saying the repressor binds to the promoterThe lac repressor binds to the OPERATOR, not the promoter. RNA polymerase binds the promoter. The repressor blocks polymerase by occupying the operator (which is between or overlapping the promoter and structural genes).
- ⚔Saying lactose binds the repressor directlyThe inducer is allolactose (an isomer of lactose produced inside the cell). Lactose itself is first converted to allolactose, which then binds the repressor. In most exam questions “lactose” is an acceptable shorthand, but understanding the allolactose step is important at A Level.
- 🌿Saying DELLA proteins bind to DNADELLA proteins bind to TRANSCRIPTION FACTORS (protein–protein interaction), not directly to DNA. It is the transcription factors (freed when DELLA is degraded) that bind to the promoter/DNA.
- 📋Confusing structural and regulatory genes in lac operonlacI = REGULATORY gene (codes for repressor protein that controls the operon). lacZ, lacY, lacA = STRUCTURAL genes (code for enzymes/proteins used to metabolise lactose). The lacI gene is outside the operon and is constitutively expressed.
- 🧬Mixing up inducible and repressible enzyme systemsInducible: OFF by default, substrate turns it ON (lac). Repressible: ON by default, product accumulation turns it OFF (trp operon). The lac operon is inducible — lactose induces enzyme synthesis.
Gene control is a high-value essay topic and connects across the entire course. Highest-yield items: all five named gene→phenotype examples (TYR/albinism; HBB/sickle cell anaemia; F8/haemophilia A; HTT/Huntington’s disease; Le/le and gibberellin/stem elongation), lac operon complete mechanism (ON and OFF states with correct component names: lacI/repressor/operator/promoter/structural genes/allolactose), DELLA degradation by gibberellin → transcription factor activation, transcription factor role in eukaryotic gene control. Synoptic links: Topic 6 (transcription/translation mechanism), Topic 15C (gibberellin/DELLA from plant coordination angle; Le/le alleles), Topic 16A (mutations in structural genes → changed phenotype), Topic 19 (recombinant DNA — inserting foreign genes into organisms requires promoter and expression).