The Roles of Genes in Determining the Phenotype: Comprehensive Study Notes

Hello Biologists! This chapter is where we link the microscopic world of DNA and proteins to the observable characteristics we see every day—your hair colour, your blood type, and even how tall a plant grows! This is the heart of A-Level Biology: understanding how the instructions encoded in your genes actually build and run a complex living organism.

Don't worry if this seems tricky at first. We will break down the essential terminology and use real-world medical and plant examples to make these abstract concepts crystal clear.

Key Takeaway from AS: Gene to Polypeptide

Remember the central dogma? A gene (a sequence of DNA nucleotides) is transcribed into mRNA, and the mRNA is translated into a polypeptide (a chain of amino acids). This polypeptide folds into a functional protein. It is this functional protein (often an enzyme or structural component) that ultimately determines your phenotype.

1. Genetic Terminology Refresher (The Vocabulary of Inheritance)

To discuss how genes determine traits, we need to speak the language of genetics fluently. Here are the must-know terms:

  • Gene: A sequence of DNA nucleotides that codes for a specific polypeptide (or functional RNA molecule).
  • Locus: The specific fixed position on a chromosome where a particular gene is located.
  • Allele: An alternative form of a gene. We inherit one allele from each parent. (e.g., the gene for eye colour has blue, brown, or green alleles).
Alleles and their Expression: Dominant vs. Recessive
  • Dominant Allele: An allele that is always expressed in the phenotype, even if only one copy is present (i.e., in heterozygous individuals). Represented by a capital letter (e.g., A).
  • Recessive Allele: An allele that is only expressed in the phenotype if two copies are present (i.e., in homozygous individuals). Represented by a lower-case letter (e.g., a).
  • Codominant Alleles: Both alleles are expressed equally in the phenotype of the heterozygous individual. (e.g., human blood groups A and B are codominant).
Genetic Combinations: Genotype vs. Phenotype
  • Genotype: The genetic makeup of an organism; the combination of alleles an individual possesses (e.g., AA, Aa, or aa).
  • Phenotype: The observable characteristics or traits of an organism, resulting from the interaction between the genotype and the environment (e.g., blue eyes, tall height).
  • Homozygous: Possessing two identical alleles for a particular gene (e.g., AA or aa).
  • Heterozygous: Possessing two different alleles for a particular gene (e.g., Aa).

Quick Memory Aid:

Geno means Genetic (the letters you have).
Pheno means Physical (the trait you see).

2. The Gene-Protein-Phenotype Relationship in Action

The phenotype (what you look like) is primarily determined by the proteins produced by your genes. If a gene has a mutation, the resulting protein might be non-functional, leading to a change in the phenotype, often seen as a genetic disorder.

Here are specific examples required by the syllabus that show how a small change in DNA can have a big impact:

2.1 TYR gene, Tyrosinase, and Albinism
  • Gene: The TYR gene codes for the enzyme tyrosinase.
  • Protein Role: Tyrosinase is an enzyme essential for the metabolic pathway that produces the pigment melanin (responsible for skin, hair, and eye colour).
  • Phenotype Change (Albinism): If an individual inherits two copies of the recessive, mutated tyr allele, the tyrosinase enzyme produced is non-functional. Since melanin cannot be synthesised, the individual displays albinism (lack of pigment).
  • Analogy: The TYR gene is the blueprint for a printing machine (Tyrosinase). If the blueprint is broken (recessive alleles), the machine doesn't work, and no ink (Melanin) is produced.
2.2 HBB gene, Haemoglobin, and Sickle Cell Anaemia
  • Gene: The HBB gene codes for the beta (β) chain of the protein haemoglobin.
  • Protein Role: Haemoglobin transports oxygen in red blood cells. It has a quaternary structure made of two alpha and two beta globin chains, each associated with an iron-containing haem group.
  • Phenotype Change (Sickle Cell Anaemia): A single base substitution mutation in the HBB gene leads to the production of a structurally altered beta chain (HbS). This causes haemoglobin molecules to stick together at low oxygen concentrations, distorting the red blood cells into a sickle shape. This results in reduced oxygen transport and blockage of capillaries (sickle cell anaemia).
2.3 F8 gene, Factor VIII, and Haemophilia
  • Gene: The F8 gene codes for Factor VIII (Factor 8).
  • Protein Role: Factor VIII is a vital protein involved in the blood clotting cascade.
  • Phenotype Change (Haemophilia): Mutations in the F8 gene (which is located on the X chromosome, making this a sex-linked disease) lead to a non-functional or deficient Factor VIII. This prevents effective blood clotting, causing Haemophilia A, where patients suffer excessive bleeding.
2.4 HTT gene, Huntington, and Huntington’s Disease
  • Gene: The HTT gene codes for the protein huntingtin.
  • Protein Role: The normal function of the huntingtin protein is not completely understood, but it is critical for nerve cell function in the brain.
  • Phenotype Change (Huntington’s Disease): This is caused by a dominant allele. The mutation is a repetition of a specific triplet sequence (CAG repeat) within the HTT gene. This leads to the production of an abnormally long and sticky huntingtin protein. This toxic protein damages nerve cells in the brain, causing movement difficulties, cognitive decline, and psychiatric problems (Huntington’s disease).

Quick Review: Gene-Protein Link
In all these examples, the gene provides the blueprint for a protein. If the blueprint is faulty (mutation), the protein malfunctions (non-functional enzyme, altered structure, or toxic accumulation), and the phenotype changes (disease/lack of pigment).

3. Genetic Control of Phenotype: Gene Regulation

Genes aren't always 'on.' Cells need a way to control which proteins are made, when, and how much, depending on internal and external conditions. This control is crucial for differentiation, development, and responding to the environment.

3.1 Structural Genes vs. Regulatory Genes
  • Structural Genes: These genes code for the proteins that actually carry out the cell's function (e.g., enzymes, structural proteins). These are the genes whose expression we want to control.
  • Regulatory Genes: These genes code for regulatory proteins (like repressors or activators) that influence the transcription of structural genes. They are the 'master switches.'
Repressible vs. Inducible Systems (Enzymes)

These terms describe how the pathway is regulated, usually in bacteria:

  • Inducible Enzymes/System: Enzymes are normally *not* produced (gene is off). Their synthesis is turned *on* (induced) when the required substrate is present. (e.g., the enzymes to break down lactose are only made when lactose is available).
  • Repressible Enzymes/System: Enzymes are normally produced (gene is on). Their synthesis is turned *off* (repressed) when the end product of the pathway accumulates.
3.2 Genetic Control in Prokaryotes: The lac Operon

Prokaryotes (like bacteria) use units called operons to coordinate gene expression for related tasks. The lac operon controls the genes needed to metabolise lactose.

The lac operon includes:

  1. Promoter: The binding site for RNA polymerase (where transcription starts).
  2. Operator: A segment of DNA where the repressor protein binds.
  3. Structural Genes (e.g., lacZ, lacY): Code for the enzymes needed to digest lactose.
Step-by-Step: How the lac Operon Works

Imagine the operon is a factory assembly line.

Scenario A: No Lactose Present (System is OFF - Repression)

  • A regulatory gene produces an active repressor protein.
  • This repressor protein binds tightly to the operator region.
  • The repressor blocks RNA polymerase from moving down the structural genes.
  • Result: The enzymes to break down lactose are not transcribed or translated. Energy is saved!

Scenario B: Lactose Present (System is ON - Induction)

  • Lactose (or a derivative of it) acts as an inducer.
  • The inducer binds to the repressor protein, causing it to change shape (conformational change).
  • The altered repressor protein can no longer bind to the operator.
  • RNA polymerase is now free to move along the DNA and transcribe the structural genes.
  • Result: Enzymes for lactose metabolism are produced, and the lactose is broken down.
3.3 Transcription Factors in Eukaryotes

Gene control is much more complex in eukaryotes (like humans and plants). Eukaryotes rely on proteins called transcription factors.

  • What they are: Transcription factors are proteins that bind to specific regions of DNA near a gene.
  • What they do: They influence the rate of transcription by RNA polymerase. They can:
    • Activate genes: Increase the rate of transcription (like turning up a dimmer switch).
    • Repress genes: Decrease the rate of transcription (like turning down a dimmer switch).
  • Importance: Transcription factors are vital in development and cell specialisation, ensuring that liver cells only express liver genes and not, say, eye genes.
3.4 Plant Hormones and Gene Control: The Gibberellin Example

The growth and development of plants, such as stem elongation, are controlled by hormones like gibberellin. This process links external signals to gene expression via a transcription factor mechanism.

The Role of Gibberellin in Stem Elongation:

Stem elongation (making the plant taller) requires the expression of genes that code for enzymes used in growth. This process is regulated by two key players: DELLA proteins and Gibberellin.

  1. DELLA Protein Repressors: Normally, DELLA proteins are active. They act as transcription factor repressors, binding to and inhibiting other factors that would otherwise promote growth genes. (The factory is naturally held shut.)
  2. Gibberellin Action: When the plant produces gibberellin (often in response to light or water), the gibberellin binds to a receptor.
  3. Repressor Breakdown: The binding causes the DELLA repressor to be broken down (degraded).
  4. Gene Activation: With the DELLA repressor gone, the growth-promoting transcription factors are now free to bind to the DNA.
  5. Result: Growth enzymes are produced, and the stem elongates. (Gibberellin removes the brake, allowing growth.)

This control mechanism is often linked to the simple Mendelian trait of stem height:

  • Dominant Allele (Le): Codes for a functional enzyme in the gibberellin synthesis pathway. High levels of gibberellin produced → DELLA repressors broken down → tall phenotype.
  • Recessive Allele (le): Codes for a non-functional enzyme. Low levels of gibberellin produced → DELLA repressors remain active → short phenotype.

Key Takeaway: Gene Regulation
Gene regulation ensures efficiency. Prokaryotes use operons (like lac) to respond immediately to nutrients. Eukaryotes use transcription factors to manage complex development and tissue specialisation.