Welcome to Topic 16: Inheritance!

Inheritance is one of the most fascinating topics in Biology. It is the study of how characteristics (traits) are passed down from parents to offspring. Whether it's the colour of your eyes or how tall you are, genetics explains it all!

In this chapter, we transition from understanding DNA structure (Topic 6) to seeing how that DNA is shuffled, packaged, and expressed across generations. Don't worry if the genetic crosses seem complicated at first; we will break down the terminology and methods step-by-step. Let's unlock the secrets of life's blueprints!

16.1 Passage of Information from Parents to Offspring: Meiosis and Variation

To understand how traits are passed on, we must first look at the process that creates the sex cells (gametes): Meiosis.

Key Terminology: Haploid and Diploid

  • Diploid (\(2n\)): A cell containing two complete sets of chromosomes, one set inherited from each parent. Most body cells (somatic cells) are diploid.
    Analogy: Think of a full deck of cards, where you have two of every number/suit.
  • Haploid (\(n\)): A cell containing only one set of unpaired chromosomes. Gametes (sperm and egg) are haploid.
    Analogy: A half deck of cards, only one of each.
  • Homologous Pair: Two chromosomes (one maternal, one paternal) that are the same size, have the same centromere position, and carry genes for the same characteristics at corresponding positions (loci).

The Need for Meiosis (Reduction Division)

If gametes were diploid, the fertilised zygote would have \(4n\) chromosomes, and the next generation \(8n\), and so on. This is unsustainable! Meiosis is essential because it is a reduction division.

It halves the chromosome number (from diploid \(2n\) to haploid \(n\)) so that when two gametes fuse during fertilisation, the correct diploid number (\(2n\)) is restored in the zygote.

The Stages of Meiosis: Two Divisions

Meiosis involves two main divisions, Meiosis I and Meiosis II, each with four stages (Prophase, Metaphase, Anaphase, Telophase). The syllabus expects you to know these main stages and the associated behaviour of the chromosomes, nuclear envelope, and spindle.

Meiosis I (The Reduction Division)

This is where the chromosome number is halved and crossing over occurs.

  1. Prophase I: Homologous chromosomes pair up (synapsis) to form bivalents. Crossing over occurs (exchange of genetic material). The nuclear envelope breaks down.
  2. Metaphase I: Homologous pairs line up randomly across the centre of the cell (equator). This is the source of random orientation (independent assortment).
  3. Anaphase I: Whole homologous chromosomes separate and are pulled to opposite poles. Crucially, sister chromatids remain joined.
  4. Telophase I: Chromosomes arrive at the poles. The cell divides (cytokinesis) resulting in two haploid cells, though each chromosome still consists of two sister chromatids.
Meiosis II (Separating Chromatids)

This division is similar to mitosis, separating the sister chromatids.

  1. Prophase II: Spindle forms in the two haploid cells.
  2. Metaphase II: Individual chromosomes (made of two chromatids) line up randomly on the equator.
  3. Anaphase II: Sister chromatids finally separate and are pulled to opposite poles.
  4. Telophase II: Chromosomes reach the poles. Cytokinesis occurs, resulting in four genetically unique haploid cells (gametes).
Quick Review: Sources of Genetic Variation

Meiosis ensures that offspring are genetically different from their parents and siblings due to three key events:

  1. Crossing Over: During Prophase I, homologous chromosomes exchange segments, creating new combinations of alleles on the chromatids.
  2. Random Orientation (Independent Assortment): During Metaphase I and Metaphase II, the orientation of homologous pairs (MI) and sister chromatids (MII) on the equator is random, leading to many different combinations in the final gametes.
  3. Random Fusion of Gametes: At fertilisation, any male gamete can fuse with any female gamete, producing a unique diploid zygote.

Key Takeaway: Meiosis halves the chromosome number and, through crossing over and random orientation, generates massive genetic variation, which is essential for evolution.

16.2 The Roles of Genes in Determining the Phenotype

Basic Genetic Terminology (The Language of Inheritance)

  • Gene: A sequence of nucleotides that codes for a specific polypeptide (protein).
  • Allele: Different versions of the same gene. (e.g., the gene for flower colour might have a 'purple' allele and a 'white' allele).
  • Locus: The specific physical position of a gene on a chromosome.
  • Phenotype: The observable characteristics of an organism, determined by both the genotype and the environment. (What the organism looks like or how it functions).
  • Genotype: The genetic makeup of an organism, referring to the combination of alleles it possesses.
  • Homozygous: Having two identical alleles for a particular gene (e.g., TT or tt).
  • Heterozygous: Having two different alleles for a particular gene (e.g., Tt).
  • Dominant Allele: An allele that is always expressed in the phenotype, even if only one copy is present (in a heterozygous state). Represented by a capital letter (e.g., T).
  • Recessive Allele: An allele that is only expressed in the phenotype if two copies are present (in a homozygous state). Represented by a lower-case letter (e.g., t).
  • Codominant Alleles: Both alleles are equally expressed in the phenotype, resulting in a combination of both traits (e.g., human blood group AB).
  • Linkage: Genes located on the same chromosome are said to be linked and are usually inherited together.
  • Test Cross: Crossing an organism with a dominant phenotype but unknown genotype (e.g., T?) with a homozygous recessive organism (e.g., tt). This reveals the unknown genotype.
  • F1/F2 Generations: F1 is the first filial generation (offspring of the parental cross). F2 is the second filial generation (offspring resulting from crossing F1 individuals).

Genetic Crosses and Predictions

1. Monohybrid Crosses (Single Trait)

These involve inheritance patterns for a single gene. The results can be predicted using a Punnett square.

Example: Simple Dominance (T = Tall, t = Short). Cross two heterozygotes (Tt x Tt).

The predicted phenotypic ratio is 3:1 (Tall : Short). The predicted genotypic ratio is 1:2:1 (TT : Tt : tt).

2. Dihybrid Crosses (Two Traits)

These crosses consider two different genes, often assuming they are on different chromosomes and assort independently.

If two characteristics assort independently (e.g., RrYy x RrYy), the expected phenotypic ratio for a simple dominant/recessive cross is typically 9:3:3:1.

3. Codominance and Multiple Alleles

Codominance occurs when both alleles are expressed. A classic example involves Multiple Alleles, such as the human ABO blood group system, controlled by three alleles: IA, IB, and i.

  • IA and IB are codominant (both expressed in AB blood group).
  • IA and IB are both dominant over i (recessive).
4. Sex Linkage

Sex-linked genes are located on the sex chromosomes (usually the X chromosome, as the Y chromosome is small and carries few genes).

Since males (XY) only have one X chromosome, they only need one copy of a recessive allele on the X chromosome to express the trait (e.g., colour blindness or haemophilia). Females (XX) need two copies.

Tip for diagrams: Always use X and Y to denote the chromosomes, and use superscripts for the alleles (e.g., XH, Xh).

5. Autosomal Linkage

When genes are located close together on the same non-sex chromosome (autosome), they are autosomal linked.

Unlike independent assortment, these genes are usually inherited together. This means the ratios obtained from a dihybrid cross will deviate significantly from the expected 9:3:3:1 ratio (unless crossing over separates them).


Analogy: If you put on socks and shoes, they are "linked" to your feet and are inherited together when you go out. They only separate if a rare event (like losing a sock) happens (crossing over).

6. Epistasis

Epistasis occurs when the allele of one gene masks or modifies the expression of another gene that is independently inherited.

This is often seen in metabolic pathways where two genes code for two separate enzymes. If the first enzyme is non-functional due to a recessive genotype, the pathway stops early, and the second gene's function is never expressed, regardless of its genotype.

Testing Your Predictions: The Chi-Squared (\(\chi^2\)) Test

In real genetic crosses, observed results rarely match the mathematically predicted (expected) ratios perfectly. We use the Chi-squared test to determine if the differences between the observed and expected results are due to chance alone, or if the differences are statistically significant (meaning something else, like linkage or selection, is happening).

The null hypothesis (\(H_0\)) states that there is no significant difference between the observed and expected results, and any deviation is due to chance.

The formula is provided in the exam (as shown in the Mathematical requirements): \[\chi^2 = \sum \frac{(O-E)^2}{E}\]

  • O = Observed frequency
  • E = Expected frequency
  • The calculated \(\chi^2\) value is compared to a critical value using degrees of freedom.
  • If the calculated \(\chi^2\) is less than the critical value (at the P=0.05 significance level), we accept \(H_0\). The results match the ratio.
  • If the calculated \(\chi^2\) is greater than the critical value, we reject \(H_0\). The results are significantly different from the expected ratio.

Key Takeaway: Genetics uses specific vocabulary and predictable ratios (like 3:1 or 9:3:3:1) for standard crosses, but concepts like linkage, codominance, and epistasis cause deviations from these simple ratios.

16.3 Genes, Proteins, and Phenotype

The central dogma of molecular biology is DNA → RNA → Protein. Genes determine the phenotype because they hold the instructions for making proteins, and proteins carry out the functions that determine the organism's characteristics.

The Gene-Protein-Phenotype Relationship (Syllabus Examples)

1. TYR Gene, Tyrosinase, and Albinism

The TYR gene codes for the enzyme tyrosinase. Tyrosinase is necessary for the production of the pigment melanin.

  • A functional *TYR* gene produces functional tyrosinase, leading to normal pigment production.
  • Albinism is often caused by a mutation in the *TYR* gene, leading to a non-functional tyrosinase enzyme. Without this enzyme, the pathway to melanin production is blocked, resulting in the phenotype of albinism (lack of pigment).
2. HBB Gene, Haemoglobin, and Sickle Cell Anaemia

The HBB gene codes for the beta-globin chain of the haemoglobin protein.

  • A specific substitution mutation in the *HBB* gene leads to the production of abnormal beta-globin (HbS).
  • This causes the haemoglobin molecules to stick together when oxygen concentration is low, distorting the red blood cells into a sickle shape, leading to the disease sickle cell anaemia.
3. F8 Gene, Factor VIII, and Haemophilia

The F8 gene codes for the protein Factor VIII, a critical clotting factor in the blood.

  • A non-functional *F8* gene results in a deficiency of Factor VIII.
  • This impairs the blood clotting cascade, leading to Haemophilia A, a sex-linked disease (located on the X chromosome) characterized by excessive bleeding.
4. HTT Gene, Huntingtin, and Huntington's Disease

The HTT gene codes for the protein huntingtin.

  • Huntington's disease is caused by a dominant mutation (an expansion of a repeat sequence) in the *HTT* gene, resulting in a misfolded, toxic huntingtin protein.
  • This toxic protein damages nerve cells in the brain, leading to the progressive neurological phenotype of Huntington's disease.

Gibberellin and Stem Elongation

Plant height is a classic example of how genes control phenotype via a metabolic pathway. In some plants, stem height is controlled by a single gene affecting the production of the hormone gibberellin.

  • Dominant allele (Le): Codes for a functional enzyme in the gibberellin synthesis pathway. This leads to high levels of gibberellin and a tall phenotype.
  • Recessive allele (le): Codes for a non-functional enzyme. This blocks gibberellin synthesis, resulting in low hormone levels and a dwarf phenotype.

16.4 Gene Control

Not all genes are expressed all the time. Cells must be able to switch genes on and off quickly and efficiently. This control of gene expression is vital for cell specialisation and responding to the environment.

Structural vs. Regulatory Genes

  • Structural Genes: Genes that code for proteins that have structural or metabolic roles in the cell (e.g., the enzymes discussed above). These are the "products."
  • Regulatory Genes: Genes that code for proteins (like transcription factors or repressors) that control the rate of expression of structural genes. These are the "switches."

Repressible vs. Inducible Enzymes

This describes how the synthesis of enzymes (proteins) is controlled:

  • Inducible Enzymes: Enzymes whose production is usually switched off, but can be "turned on" (induced) by the presence of a specific substrate. (Think of a light switch starting off, but you turn it on when you need light).
  • Repressible Enzymes: Enzymes whose production is usually switched on, but can be "turned off" (repressed) by the presence of an end product. (Think of a factory running non-stop until the warehouse fills up, forcing production to halt).

Genetic Control in Prokaryotes: The lac Operon

In prokaryotes (like bacteria), genes that work together are grouped into a functional unit called an operon. The lac operon controls the production of enzymes needed to break down lactose (an inducible system).

The key components are:

  • Structural Genes: Code for the enzymes (e.g., lactase) needed for lactose metabolism.
  • Operator (O): A DNA sequence where the repressor protein binds.
  • Promoter (P): A DNA sequence where RNA polymerase binds to start transcription.
  • Regulatory Gene: Codes for the repressor protein.
How the lac Operon works (Inducible system):
  1. Lactose Absent: The regulatory gene produces an active repressor protein. The repressor binds to the operator region.
  2. Since the repressor physically blocks the promoter, RNA polymerase cannot bind. Transcription of the structural genes is prevented (switched off).
  3. Lactose Present: Lactose acts as an inducer. It binds to the repressor protein, causing it to change shape and detach from the operator.
  4. RNA polymerase is now free to bind to the promoter and transcribe the structural genes. Enzymes are made, and lactose is broken down (switched on).

Gene Control in Eukaryotes: Transcription Factors

Eukaryotic gene control is much more complex, often involving specific proteins called transcription factors.

Transcription factors are regulatory proteins that bind to specific DNA sequences (often upstream of the structural gene) to control the rate of transcription.

  • They can decrease the rate (acting as a repressor).
  • They can increase the rate (acting as an activator).

Gibberellin and Gene Activation (Eukaryote Example)

This is a specific example showing how a hormone activates genes via transcription factors. Gibberellin is essential for the germination of barley seeds.

  1. In the absence of gibberellin, DELLA protein repressors are active and bind to the factors that promote transcription, thereby inhibiting gene expression.
  2. When gibberellin is present (e.g., during germination), it triggers the breakdown of these DELLA protein repressors.
  3. Once DELLA is removed, the transcription factors are free to bind to the DNA, promoting the transcription of genes needed for germination (like amylase production).
Quick Review: Gene Control

Gene control allows cells to be efficient. Prokaryotes use the lac operon as an "on/off" switch driven by repressors. Eukaryotes use transcription factors as volume controls, often regulated by hormones like gibberellin, which controls protein repressors (DELLA).