12.3 Mutation
Mutation is a spontaneous and random alteration in the genetic material (DNA) of an organism's cells. While mutations occur naturally at low rates, environmental agents known as mutagens can significantly accelerate the occurrence of these genetic changes. Depending on whether the change affects specific nucleotide sequences within a single gene or alters the overall structure and number of entire chromosomes, mutations can produce varied phenotypic outcomes ranging from mild variations to severe inherited disorders.
Learning Objectives
- State the definitions of mutation, mutagen, and mutant.
- Identify the three types of mutagens: physical, chemical, and biological agents.
- Describe gene mutation (point mutation) and differentiate between base substitution, base insertion, and base deletion.
- Explain diseases caused by gene mutations, including sickle cell anaemia, cystic fibrosis, thalassemia, and albinism.
- Describe chromosomal mutations, encompassing chromosomal aberrations (deletion, duplication, inversion, translocation) and changes in chromosome number.
- Explain the mechanism of nondisjunction during meiosis I and meiosis II and its consequences on gamete formation.
- Describe the characteristics of human disorders resulting from abnormal autosome and sex chromosome numbers or structures (Down syndrome, Cri du chat syndrome, Klinefelter syndrome, Jacob syndrome, and Turner syndrome).
- Compare and contrast mutations occurring in somatic cells with mutations occurring in gametes.
Types of Chromosomal Aberrations and Nondisjunction Pathways
Structural rearrangements in chromosomes alongside the gametic outcomes of nondisjunction during meiosis I versus meiosis II.
Deletion
A part or segment of a chromosome is deleted or lost, leading to the loss of several genes.
Duplication
A segment of a chromosome is copied, resulting in repetitive gene sequences.
Inversion
A segment of a chromosome breaks off, rotates \(180^\circ\), and rejoins, reversing the DNA sequence.
Translocation
A segment of a chromosome is broken off and joins onto another non-homologous chromosome.
Short Explanation
Definition of Terms
Mutation is a spontaneous and random change of genetic material, namely DNA of the cell in an organism. A mutagen is a substance or agent that causes mutation or increases the mutation rate to a dangerous level. The mutant is the new genetic material produced by mutation, which can exist as a mutant gene, mutant cell, mutant organelle, or mutant individual.
Types of Mutagens
Physical agents: Ultraviolet (UV) light from the sun, and ionising rays such as X-rays, alpha rays, and beta rays.
Chemical agents: Carcinogens in cigarette smoke, food preservatives, formaldehyde, and benzene.
Biological agents: Viruses and bacteria.
Gene Mutation (Point Mutation)
A change in the nucleotide base sequence of a single gene. It alters the triplet codon used to synthesise amino acids during protein synthesis, leading to changes in protein structure that render the resulting protein non-functional or abnormal.
Mechanisms of Gene Mutation
Base substitution: One nucleotide base is replaced by another base, which can synthesise a different amino acid.
Base insertion: One or more base pairs are added into the DNA sequence, altering the subsequent reading frames and synthesising completely new amino acids.
Base deletion: One or more base pairs are lost from the DNA sequence, altering subsequent triplet codes and synthesising new amino acids.
Genetic Diseases Caused by Gene Mutations
Sickle cell anaemia (base substitution): Affects the gene responsible for haemoglobin synthesis. Red blood cells become crescent-shaped and malformed, reducing their oxygen-carrying capacity.
Cystic fibrosis (base insertion): Affects secretory glands and mucus production.
Thalassemia (base deletion): Causes abnormal formation of haemoglobin and destruction of red blood cells.
Albinism: Caused by a mutation in a gene responsible for producing pigments in the skin, hair, and eyes, resulting in the complete absence of these pigments.
Haemophilia: An inherited bleeding disorder caused by a defective blood-clotting gene.
Chromosomal Mutation
Chromosomal mutations involve changes either in the structure of chromosomes or in the total number of chromosomes.
Changes in chromosomal structure (chromosomal aberrations): Occurs when the gene sequence or arrangement within a chromosome is altered — deletion, duplication, inversion, or translocation.
Changes in chromosomal number: A diploid organism loses or gains one or more chromosomes. Caused by nondisjunction — the failure of homologous chromosomes to separate during anaphase I, or the failure of sister chromatids to separate during anaphase II of meiosis. The primary cellular cause is that spindle fibres fail to form properly during meiosis.
Outcomes of Nondisjunction
Nondisjunction during meiosis I produces four abnormal gametes: \(n+1, n+1, n-1, n-1\).
Nondisjunction during meiosis II produces two abnormal gametes: \(n+1, n-1\), and two normal gametes: \(n, n\).
Nondisjunction during oogenesis or spermatogenesis produces abnormal gametes that, upon fertilisation with normal gametes, produce zygotes with abnormal chromosome numbers.
Characteristics of Diseases Caused by Chromosomal Mutation
Down Syndrome: \((2n + 1) = 47\) (Trisomy 21; possesses three copies of chromosome 21). Characteristics: slanted eyes, flat nose, protruding tongue, broad forehead, and mental retardation. Foetal risk increases with maternal age.
Cri du chat syndrome: Partial deletion of the short arm of chromosome number 5. Characteristics: high-pitched cry of affected infants resembling a meowing kitten, delayed development, mental and physical retardation; most patients die in childhood.
Klinefelter Syndrome: \((2n + 1) = 47\) (\(44 + \text{XXY}\)). Phenotype: sterile male with underdeveloped, small testes that do not produce sperm; feminine characteristics such as enlarged breast tissue and high-pitched voice; elongated limbs (long arms and legs).
Jacob Syndrome: \((2n + 1) = 47\) (\(44 + \text{XYY}\)). Phenotype: taller than average male, severe facial acne, speech acquisition delays, learning disabilities, and weak muscle tone (hypotonia).
Turner Syndrome: \((2n - 1) = 45\) (\(44 + \text{XO}\)). Phenotype: sterile female lacking secondary sexual characteristics, undeveloped breasts and ovaries, webbed neck, and low IQ.
Mutation in Somatic Cells vs Gametes
Mutation in somatic cells: Occurs in somatic cells (e.g., skin cells, eye cells, bone marrow cells). Cannot be inherited by the next generation. Disease remains restricted only to the individual experiencing the mutation (e.g., blood cancer/leukaemia from bone marrow mutation, diseases of the nervous system).
Mutation in gametes (germline): Occurs in germ cells that divide to produce gametes (secondary oocytes or sperms). Can be transmitted and inherited by the next generation. Disease affects the individual and is inherited by descendants (e.g., all inherited conditions such as thalassemia).
Try to Answer First
Answer in your mind, then press “Check Answer”.
What is the difference between a mutagen and a mutant?
Why does nondisjunction during meiosis I produce different gametes compared to nondisjunction during meiosis II?
Why can thalassemia be inherited by offspring while blood cancer originating from bone marrow cells cannot?
Common Mistakes
- Confusing chromosomal deletion with base deletion: Base deletion involves removing single nucleotide bases from a gene sequence, whereas chromosomal deletion involves losing an entire segment of a chromosome containing multiple genes.
- Stating that nondisjunction only occurs in mothers: While maternal age correlates with increased risk, nondisjunction can occur during either oogenesis or spermatogenesis.
- Assuming an OY zygote survives: Zygotes with an OY sex chromosome constitution lack the essential X chromosome and die during development.
- Confusing Klinefelter syndrome (\(44 + \text{XXY}\)) with Jacob syndrome (\(44 + \text{XYY}\)).
Concept Misunderstandings
All mutations are immediately inherited by children.
Only mutations occurring in germ cells that form gametes (sperms or secondary oocytes) are inheritable. Mutations in somatic tissues (e.g., skin, bone marrow) are not passed down.
Gene mutations always change the whole chromosome structure.
Gene mutations (point mutations) change only the nucleotide base sequence of a single gene without changing the visual structure or karyotype of the chromosome.
A base substitution always changes every downstream amino acid in the polypeptide chain.
Base substitution alters only the specific triplet codon where the replacement occurs; base insertions and base deletions shift the reading frame and change all subsequent codons downstream.
Summary
- Mutation is an unpredictable change in DNA caused by physical, chemical, or biological mutagens.
- Gene mutations (substitutions, insertions, deletions) alter base sequences and disrupt protein synthesis, causing conditions like sickle cell anaemia and thalassemia.
- Chromosomal mutations involve structural aberrations (deletion, duplication, inversion, translocation) or numerical changes caused by meiotic nondisjunction (e.g., Down, Klinefelter, Turner, and Jacob syndromes).
- Gametic mutations are heritable across generations, whereas somatic mutations affect only the individual.
Short Activity
Objective: identify chromosomal aberrations, chromosomal compositions, and key mutation terms.
A. Objective Quiz
Which of the following conditions is caused by a structural chromosomal aberration involving a partial deletion of the short arm of chromosome number 5?
A human female with Turner syndrome has which of the following chromosomal compositions?
B. Fill in the Blanks
The failure of homologous chromosomes or sister chromatids to separate during meiosis is known as .
Down syndrome is caused by the presence of three copies of chromosome number .
C. Matching / Drag and Drop
Drag each structural aberration to its correct description. On a phone, tap a choice first, then tap the matching box. Tap the Answer Choices area to return a selected item.
C. Match the Structural Aberration to Its Description
Write the correct structural aberration next to each description.
| Description | Structural Aberration |
|---|---|
| 1. A part or a segment of chromosome is deleted or lost (loss of a few genes). | |
| 2. A part of a chromosome is copied which causes repetition of gene sequence. | |
| 3. A segment of chromosome is reversed end to end at 180° then rejoins. | |
| 4. Part of the chromosome is cut, then joins to another non-homologous chromosome. |
Answer choices: Deletion • Duplication • Inversion • Translocation
