The roles of genes in determining phenotype

1. Overview

The link between a gene and the appearance of an organism is indirect: a gene is a length of DNA whose nucleotide sequence codes for the amino acid sequence of a polypeptide. That polypeptide folds into a protein, and proteins (as enzymes, structural molecules, transport proteins or signalling molecules) build and run the body, which produces the phenotype.

A mutation that changes the nucleotide sequence can change the protein, and so change the phenotype. This section traces that gene → protein → phenotype pathway through four human examples (albinism, sickle cell anaemia, haemophilia, Huntington's disease) and one plant example (gibberellin and stem elongation, controlled by the Le/le alleles).

Key Definitions

• Gene: a length of DNA that codes for the sequence of amino acids in a polypeptide (and so for a protein).
• Allele: an alternative version of a gene, differing in its nucleotide (base) sequence and often producing a different form of the protein.
• Phenotype: the observable characteristics of an organism, produced by the interaction of its genotype with the environment.
• Mutation: a change in the nucleotide (base) sequence of DNA, which may alter the amino acid sequence and so the structure and function of the protein.
• Recessive allele: an allele whose effect is only seen in the phenotype when two copies are present (homozygous), often because it codes for a non-functional or absent protein.
• Dominant allele: an allele whose effect is seen in the phenotype when one copy is present, often because it codes for a functional protein or a faulty protein with a harmful effect.
• Gibberellin: a plant growth regulator that promotes cell elongation and division in stems, causing stems to grow taller.
• Carrier: a heterozygous individual who has one copy of a recessive allele, does not show the condition, but can pass the recessive allele to offspring.

Content

The gene to phenotype pathway

A gene's nucleotide sequence is transcribed into mRNA and translated into a polypeptide with a specific primary structure (amino acid sequence). The primary structure determines how the polypeptide folds into its three-dimensional shape, which determines the protein's function. The protein then carries out a role — catalysing a reaction, carrying oxygen, helping blood to clot — that contributes to the phenotype.

A mutation changes the nucleotide sequence, not the gene's "order of amino acids" directly. A changed nucleotide sequence may change the amino acid sequence (primary structure), which can change the protein's shape and function, and therefore the phenotype. Always describe the chain in this order:

nucleotide sequence → amino acid sequence → protein structure → protein function → phenotype

Albinism: the TYR gene and tyrosinase

The TYR gene codes for the enzyme tyrosinase, which catalyses an early step in making the pigment melanin from the amino acid tyrosine. A recessive allele of TYR codes for a non-functional (or absent) tyrosinase. An individual homozygous for this recessive allele cannot catalyse melanin production, so little or no melanin is made. The phenotype is albinism — very pale skin, hair and eyes.

Here a faulty enzyme blocks a metabolic pathway, so the product (melanin) is not formed.

Sickle cell anaemia: the HBB gene and haemoglobin

The HBB gene codes for the beta-globin polypeptide of haemoglobin. A point mutation changes a single nucleotide, which changes one amino acid in beta-globin (a normal glutamic acid is replaced by valine). This small change in primary structure makes the haemoglobin molecules stick together when oxygen concentration is low, distorting red blood cells into a rigid sickle shape.

Sickled cells carry less oxygen, are broken down faster (causing anaemia) and can block capillaries. This shows how a change to just one amino acid can have a large effect on the phenotype.

Haemophilia: the F8 gene and factor VIII

The F8 gene codes for factor VIII, a protein needed in the cascade of reactions that makes blood clot. A recessive, faulty allele produces little or no functional factor VIII, so the clotting cascade cannot be completed normally. The phenotype is haemophilia: blood clots very slowly, so bleeding is prolonged.

The F8 gene is on the X chromosome, which is why this condition is far more common in males (they have only one X chromosome, so a single faulty allele is enough to cause it). Here a missing/non-functional protein removes a step needed for normal function.

Huntington's disease: the HTT gene and huntingtin

The HTT gene codes for the huntingtin protein, found mainly in nerve cells. The faulty allele contains an expanded, repeated sequence of three bases (a triplet repeat), so the huntingtin protein it codes for is abnormally long. This altered protein gradually damages and kills nerve cells in the brain, producing the symptoms of Huntington's disease (loss of movement control and cognitive decline). Symptoms usually appear in middle age (late onset).

Inheritance is the key difference from the other three examples:

• The faulty allele is dominant, so the disease appears even with only one copy.
• A faulty protein actively causes harm, rather than a protein simply being missing or non-functional.

The late onset is important in pedigree questions: because symptoms appear after reproductive age, affected people often have children before they know they carry the allele, so the harmful dominant allele continues to be passed on. It also means an affected child must have an affected parent (the allele is dominant, so it cannot skip a generation).

Gibberellin and stem elongation: the Le and le alleles

In plants, the growth regulator gibberellin stimulates cell division and cell elongation in the stem, making stems grow tall. Gibberellin is produced through a multi-step synthesis pathway, and one step is catalysed by an enzyme coded for by the Le gene.

• The dominant allele, Le, codes for a functional enzyme. This enzyme catalyses a step that produces active gibberellin, so plants with at least one Le allele make active gibberellin, their stems elongate, and they are tall.
• The recessive allele, le, codes for a non-functional enzyme (a faulty version that cannot catalyse the step). Plants that are homozygous le le cannot complete the pathway, so they make little or no active gibberellin, their stem cells do not elongate normally, and the plants are short (dwarf).

This is a clear example of the gene → enzyme → product → phenotype pathway in a plant: whether the enzyme works decides whether the active hormone is made, and the hormone decides stem height. It also shows why the tall allele is dominant — a single functional copy makes enough enzyme to produce active gibberellin.

Summary of the four human examples

The table below brings the four conditions together so you can compare them quickly when revising:

Condition	Gene	Protein	Normal role of protein	What the faulty allele does	Allele type
Albinism	TYR	Tyrosinase	Catalyses a step in making melanin	Non-functional enzyme, so little/no melanin made	Recessive
Sickle cell anaemia	HBB	Beta-globin (in haemoglobin)	Carries oxygen in red blood cells	One amino acid changed, so haemoglobin clumps and cells sickle	Recessive
Haemophilia	F8	Factor VIII	Needed in the blood-clotting cascade	Little/no functional factor VIII, so blood clots slowly	Recessive (X-linked)
Huntington's disease	HTT	Huntingtin	Function in nerve cells	Abnormally long protein actively damages nerve cells	Dominant

Notice the pattern: three conditions (albinism, sickle cell, haemophilia) arise from recessive alleles coding for non-functional or absent proteins, while Huntington's arises from a dominant allele coding for a harmful protein.

Worked example

Exam-style question: A pea plant homozygous for the recessive allele le has short stems, while plants carrying the dominant allele Le have tall stems. Using your knowledge of the gibberellin synthesis pathway, explain why the le le plants are short. [4]

Model answer:

• The Le gene codes for an enzyme that catalyses a step in the gibberellin synthesis pathway.
• The recessive allele le codes for a non-functional enzyme, so this step cannot be catalysed.
• Homozygous le le plants therefore make little or no active gibberellin.
• Without gibberellin, the stem cells do not elongate normally, so the plants are short / dwarf.

Worked example

Exam-style question: Haemophilia is caused by a recessive allele of the F8 gene on the X chromosome. A woman who is a carrier ($X^H X^h$) has children with a man who does not have haemophilia ($X^H Y$). Give the possible genotypes and phenotypes of their children, and explain why haemophilia is much more common in males than in females. [5]

Model answer:

• Cross: mother $X^H X^h \times$ father $X^H Y$.
• The four equally likely offspring genotypes are $X^H X^H$, $X^H X^h$, $X^H Y$ and $X^h Y$.
• Daughters: $X^H X^H$ (unaffected) and $X^H X^h$ (unaffected carrier) — none have haemophilia.
• Sons: $X^H Y$ (unaffected) and $X^h Y$ (has haemophilia) — so half of sons, on average, are affected.
• Haemophilia is more common in males because they have only one X chromosome, so a single recessive allele ($X^h Y$) is enough to cause the condition; a female needs two copies ($X^h X^h$) for it to show, which is much less likely.

Key Equations

This topic is qualitative; there are no equations to learn. Focus on describing the gene → protein → phenotype pathway accurately for each example.

Common Mistakes to Avoid

• Saying a mutation "changes the order of amino acids in the gene". A gene is made of DNA, so a mutation changes the nucleotide (base) sequence. This may then change the primary structure (amino acid sequence) of the polypeptide.
• Claiming the gene itself "does" the job. Make clear that the gene codes for a protein, and it is the protein (enzyme, haemoglobin, factor VIII, huntingtin) that produces the effect on the phenotype.
• Forgetting why an allele is recessive or dominant. Albinism, haemophilia and the le allele are recessive because they code for non-functional or absent proteins, so one working copy masks them; Huntington's is dominant because the faulty protein actively causes harm even in one copy.
• Describing sickle cell as "a big change to the gene". It is a single nucleotide change that alters one amino acid in beta-globin — emphasise how a tiny change has a large effect.
• Assuming different cell types contain different genes. Every somatic nucleus in an organism carries the full set of genes; what differs between cells is which genes are expressed, not which genes are present.
• Saying that a gene "controls" or "switches on" another gene directly. It is the protein product that does the controlling — for example, a gene that regulates expression codes for a transcription factor (a protein), and it is this protein that binds to DNA to switch genes on or off. Keep the logic consistent: genes code for proteins, and proteins do the work.
• Mixing up gibberellin's effect. Gibberellin promotes stem elongation; lack of it (in le le plants) gives short stems, so do not state that gibberellin shortens stems.

Exam Tips

• Watch the command word — this topic sets two question shapes that are answered differently. "Describe/explain how the gene leads to the phenotype" wants the chain, with a mark per link in the nucleotide → amino acid → protein structure → protein function → phenotype order. "Explain why the allele is dominant/recessive" wants the protein-functionality argument instead: recessive because one working copy still makes enough functional protein, dominant because the faulty protein actively harms even in one copy. Give the answer the command word asks for, not just the chain.
• Learn each example as a complete chain: gene → protein it codes for → what that protein normally does → what goes wrong → resulting phenotype. Marks are usually given for each correct link.
• Use the exact protein names (tyrosinase, beta-globin/haemoglobin, factor VIII, huntingtin) and gene names (TYR, HBB, F8, HTT) — vague answers like "a clotting protein" lose precision marks.
• For metabolic-pathway examples (albinism, gibberellin), state that a non-functional enzyme blocks a step, so the product is not made — this is the key idea you need to show.
• When asked to compare the conditions, note that three (albinism, sickle cell, haemophilia) involve non-functional/absent proteins from recessive alleles, while Huntington's involves a harmful protein from a dominant allele. The summary table above is built around exactly this comparison.
• In plant questions, link the functional vs non-functional enzyme directly to active gibberellin present vs absent, and then to tall vs short — do not stop at "the enzyme is faulty".