12.3 - Mutation

Definition of Mutation, Mutagen, and Mutant

• Mutation: A spontaneous and random change of genetic material, namely DNA, in the cell of an organism.
• Mutation occurs spontaneously under natural conditions.
• Mutagen: A substance that causes mutation or increases the mutation rate to a dangerous level.
• Mutant: New genetic material produced by mutation; it can exist as a mutant gene, mutant cell, mutant organelle or mutant individual.

Types of Mutagens

• Physical agents: Ultraviolet rays 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.
• A somatic-cell mutation in bone-marrow cells can cause blood cancer.

Types of Mutations

• The two types are gene mutation and chromosomal mutation.

Gene Mutation

• A change in the nucleotide base sequence of a gene; also known as a point mutation.
• The change alters the genetic code used to synthesise amino acids.
• Protein structure changes and the new protein cannot function.

Mechanisms of Gene Mutation

• Base substitution: One nucleotide base is substituted; a different amino acid is synthesised.
• Base insertion: A nucleotide base is inserted; new amino acids are synthesised.
• Base deletion: A nucleotide base is deleted; new amino acids are synthesised.

Genetic Diseases Caused by Gene Mutation

• Gene mutations cause thalassemia, cystic fibrosis, sickle cell anaemia, albinism and haemophilia.
• Base substitution: Sickle cell anaemia.
• Base insertion: Cystic fibrosis.
• Base deletion: Thalassemia.
• Sickle cell anaemia:
  • caused by mutation of a gene responsible for haemoglobin synthesis;
  • red blood cells are not properly formed; and
  • some red blood cells are normal while others are crescent-shaped.
• Albinism:
  • an affected individual is an albino;
  • caused by mutation of a gene responsible for producing pigments of the skin, hair and eyes; and
  • these pigments are not produced in an albino.

Chromosomal Mutation

• Involves changes to chromosomal structure or chromosome number.
• Can change the characteristics of an organism.

1. Changes in Chromosomal Structure (Chromosomal Aberration)

• Changes in chromosomal structure alter the gene sequence and cause chromosomal aberration.
• Deletion: A chromosome end or segment breaks and is lost, causing the loss of a few genes.
• Duplication: A chromosome segment is copied, causing repetition of a gene sequence.
• Inversion: A chromosome segment breaks, rotates through $180^{\circ }$ and rejoins, changing the gene sequence.
• Translocation: A chromosome segment breaks and joins another non-homologous chromosome.

2. Changes in Chromosome Number

• A diploid organism loses or gains one or more chromosomes.
• Homologous chromosomes fail to separate during anaphase I, or sister chromatids fail to separate during anaphase II.
• Failure to form normal spindle fibres during meiosis may cause this nondisjunction.
• Gametes may lose or gain one or more chromosomes.
• Nondisjunction during spermatogenesis or oogenesis can produce an abnormal gamete.
• Fertilisation involving an abnormal gamete produces a zygote that develops into an individual with abnormal characteristics and a changed phenotype.

Genetic Diseases Caused by Chromosomal Mutations

• Down syndrome:
  • autosomal abnormality, $(2n+1)=47$, with three chromosome 21s; and
  • slant eyes, flat nose, protruding tongue, broad forehead and usually mental retardation.
• Cri du chat syndrome:
  • structural change caused by partial deletion on the short arm of chromosome 5; and
  • a meowing-kitten-like cry in infancy, delayed development, mental and physical retardation; most patients die during childhood.
• Klinefelter syndrome:
  • sex-chromosome abnormality, $(2n+1)=47$, $44+XXY$; and
  • a sterile male with small testes that fail to produce sperm, voice and chest similar to a woman, and long legs and hands.
• Jacob syndrome:
  • sex-chromosome abnormality, $(2n+1)=47$, $44+XYY$; and
  • taller than a normal male, severe facial acne, delayed speech, learning disability and weak muscles (hypotonia).
• Turner syndrome:
  • sex-chromosome abnormality, $(2n-1)=45$, $44+XO$; and
  • a sterile female with underdeveloped breasts and ovaries, lack of secondary female characteristics, a weblike neck and low IQ.

Mutation of Somatic Cells and Gametes

Similarities

• Both can undergo mutation and produce variation in a population.

Differences

• Mutation in somatic cells:
  • involves body cells such as skin cells and eye cells;
  • cannot be inherited by the next generation;
  • disease occurs only in the individual with the mutation; and
  • example: disease related to the nervous system.
• Mutation in gametes:
  • involves germ cells that produce secondary oocytes or sperm;
  • can be inherited by the next generation;
  • disease occurs in the individual with the mutation and is inherited by descendants; and
  • example: inherited diseases such as thalassemia.