Variation and Selection

Lessons

Senior 3 · Biology

Variation and Selection

5 lessons

Lesson 2 of 5

Mutations and their types

25 min

One letter in three billion

The DNA in one set of human chromosomes is about three billion bases long. In people with sickle-cell disease, just one base in the gene for part of haemoglobin is different: where most people have the triplet GAG, they have GTG. That single change puts the amino acid valine in place of glutamic acid in each haemoglobin chain. When oxygen is low, the changed haemoglobin molecules stick together into long fibres and pull the red blood cells into a stiff, curved "sickle" shape. Sickle cells can block small blood vessels, causing pain and damage to organs, and they break down quickly, causing anaemia.

A change like this in DNA is a mutation. Mutations are the only source of brand-new alleles, so they are the raw material of all inherited variation.

(A) Normal red blood cells, disc-shaped, flowing freely in a blood vessel. (B) Sickle cells, stiff and curved, sticking together and blocking blood flow; the inset shows the abnormal haemoglobin forming strands inside the cell. Illustration: National Heart, Lung, and Blood Institute (NHLBI), public domain, via Wikimedia Commons.

Definition

Mutation: a random change in the DNA of a cell, either in a gene or in the structure or number of chromosomes.

Gene (point) mutation: a change in the base sequence of one gene, which may produce a new allele.

Chromosome mutation: a change in the structure of a chromosome, or in the number of chromosomes in a cell.

Mutagen: anything that increases the rate of mutation, such as X-rays or ultraviolet light.

Gene mutations

The bases of a gene are read in groups of three, called triplets; each triplet codes for one amino acid in the protein. A gene mutation changes the bases in one of three ways (Figure 1):

Figure 1. The three kinds of gene mutation, in a short stretch of DNA read in triplets. The changed base is dark orange; triplets altered by a frameshift are light orange.

Substitution: one base is replaced by another. Only one triplet changes, so at most one amino acid changes. Sickle-cell disease is caused by a substitution.
Insertion: an extra base is added.
Deletion: a base is lost.

An insertion or deletion shifts the reading of every triplet after it: a frameshift. The protein made usually has many wrong amino acids and does not work, so insertions and deletions usually have bigger effects than substitutions.

Worked example

Worked example 1: name the mutation. A sentence of three-letter words behaves like a gene read in triplets. The original is THE CAT SAW THE DOG. Name each mutation and say how much of the "message" is damaged.

Mutated version	Mutation	Effect
THE CAT SAW THE HOG	substitution (D to H)	one word changed; the rest still reads
THE CAT SAW XTH EDO G	insertion (X)	every word after the X is nonsense
THE CTS AWT HED OG	deletion (A)	every word after the gap is nonsense

Frameshifts (insertion and deletion) wreck everything that follows; a substitution changes only one "word", and sometimes not even that, because some triplets code for the same amino acid.

Chromosome mutations

Changes in structure happen when chromosomes break and rejoin wrongly, often during crossing over (Figure 2).

Figure 2. Changes in chromosome structure. Each letter stands for a section of the chromosome carrying several genes.

Changes in number happen when chromosomes fail to separate properly in meiosis. This is called non-disjunction: both chromosomes of a pair go into the same cell, so one gamete has an extra chromosome and another has one missing.

Down syndrome is caused by an extra chromosome 21, often from an egg with 24 chromosomes. The person has 47 chromosomes in each body cell (trisomy 21). People with Down syndrome have some degree of learning difficulty and may have health problems such as heart defects; with good care and support, many go to school, work and take full part in their communities. The chance of non-disjunction rises with the mother's age.
Polyploidy is having more than two complete sets of chromosomes. It is rare in animals but common in crop plants. Bread wheat has six sets ( $6 n = 42$ ). Most cultivated bananas have three sets (triploid, $3 n = 33$ ): three sets cannot pair evenly in meiosis, so the plants make almost no viable seeds, and farmers grow new plants from suckers.

Worked example

Worked example 2: counting chromosomes after non-disjunction. In meiosis in an ovary, the two chromosomes 21 fail to separate. (a) How many chromosomes are in the two kinds of egg that can result? (b) Each is fertilised by a normal sperm. How many chromosomes does each zygote have?

Solution

A normal egg has $n = 23$ . The egg that receives both chromosomes 21 has $23 + 1 = 24$ ; the egg that receives neither has $23 - 1 = 22$ .
With a normal sperm (23): $24 + 23 = 47$ , trisomy 21 (Down syndrome); $22 + 23 = 45$ , a zygote missing a chromosome 21, which does not usually develop.

What causes mutations, and what do they do?

Mutations happen spontaneously, as rare mistakes when DNA is copied before cell division. Mutagens raise the rate:

Ionising radiation: X-rays, gamma rays and radiation from radioactive substances.
Ultraviolet light, from the Sun: it can cause skin cancer.
Some chemicals, such as many substances in tobacco smoke.

Effect	Example
Harmful (most mutations that change a protein)	sickle-cell disease; haemophilia; cancers
Neutral (no effect on the organism)	a substitution that gives the same amino acid
Beneficial (rare)	resistance of bacteria to an antibiotic; resistance of insects to an insecticide

Only mutations in gametes, or in the cells that make them, are passed to offspring. A mutation in a body cell, such as a skin cell damaged by sunlight, may cause cancer in that person but is not inherited.

Warning

Safety. Keep exposure to mutagens low: X-rays are taken only when needed, and radiographers stand behind a screen or wear lead aprons; protect skin and eyes from strong sun with clothing and shade; do not smoke. A mutation is not a "superpower" and is not chosen by the organism; it is a random change, and most changes that alter a protein are harmful.

Mutations (updated), from the Amoeba Sisters. Watch for substitution, insertion and deletion, and why an insertion or deletion causes a frameshift.

Tip

Gene or chromosome? If the change is in the letters (bases) of one gene, it is a gene mutation. If whole sections or whole chromosomes are lost, gained, turned round or moved, it is a chromosome mutation.

✦

Practice: mutations

Define (a) mutation, (b) mutagen. Give two examples of mutagens.
The base sequence TAC GGA TTC becomes TAC GGT TTC. Name the type of gene mutation, and say how many triplets have changed.
Explain why a deletion near the start of a gene usually has a bigger effect than a substitution.
Name the type of chromosome mutation shown by: (a) ABCDEF becoming ABEDCF; (b) ABCDEF becoming ABCDEEF.
A person has 47 chromosomes, with three copies of chromosome 21. Name the condition and explain how non-disjunction can cause it.
A wild relative of a crop has $2 n = 14$ . A tetraploid ( $4 n$ ) form appears. How many chromosomes are in its body cells?
A man worked for years with X-rays without protection and later developed a skin cancer on his hand. Will his children inherit this mutation? Explain.
Explain why mutation is important for the variation of a species, even though most mutations are harmful.

Show answersHide answers

(a) A random change in the DNA, in a gene or in the structure or number of chromosomes. (b) Something that increases the rate of mutation, for example X-rays, gamma rays, ultraviolet light, or chemicals in tobacco smoke.
Substitution (A replaced by T); one triplet has changed (GGA to GGT).
A deletion shifts the reading frame, so every triplet after it is read wrongly and the protein is badly changed. A substitution changes at most one triplet and one amino acid.
(a) Inversion (CDE turned round to EDC). (b) Duplication (section E repeated).
Down syndrome (trisomy 21). In meiosis the two chromosomes 21 fail to separate, so a gamete gets 24 chromosomes; fertilisation by a normal gamete (23) gives 47.
$n = 7$ , so $4 n = 28$ .
No. The mutation is in skin (somatic) cells, not in his gametes or the cells of his testes, so it is not passed on.
Mutation is the only source of new alleles. Meiosis and fertilisation only reshuffle existing alleles; without mutation there would be no new variation for natural selection to act on, and the rare beneficial mutations allow populations to adapt.

Key points

Gene mutations: substitution (one triplet changes), insertion and deletion (frameshift).
Chromosome mutations: deletion, duplication, inversion and translocation in structure; non-disjunction (for example trisomy 21) and polyploidy in number.
Mutagens include ionising radiation, ultraviolet light and some chemicals.
Most mutations are harmful or neutral; only those in gametes are inherited; mutation is the source of new alleles.

Sources and credits

Illustration: Sickle cell 01, National Heart, Lung, and Blood Institute (NHLBI), public domain, via Wikimedia Commons.
Video: Mutations (Updated), Amoeba Sisters, embedded from YouTube.

Written by Ganzaa: the text, Figures 1 and 2, the tables, the worked examples and the practice questions.

1One letter in three billion

2Gene mutations

3Chromosome mutations

4What causes mutations, and what do they do?

One letter in three billion

Gene mutations

Chromosome mutations

What causes mutations, and what do they do?