AQA A-level Biology: Mutation and Meiosis (7402)

This guide covers AQA A-level Biology (7402) section 3.4.3, Genetic diversity can arise as a result of mutation or during meiosis, as set out in the AQA AS and A-level Biology specification for first teaching 2015. Section 3.4.3 sits in topic 4, which is also AS content, and the assessment overview lists topics 1 to 4 for A-level Paper 1 and Paper 3. For the other pages in this unit see the revision notes and the practice questions. Course pages: AQA A-level Biology hub and the printable checklist. To find weak spots first, try the free diagnostics.

What the specification asks for

Statement in 3.4.3	What you must be able to do
Gene mutations	Describe base deletion and base substitution; say they can arise spontaneously during DNA replication
Degenerate code	Explain why not every substitution changes the amino acid sequence
Mutagenic agents	State that they increase the rate of gene mutation
Non-disjunction	Explain how it changes chromosome number during meiosis
Meiosis	Show how two nuclear divisions give four haploid cells from one diploid cell, and how independent segregation and crossing over make them different
Skills	Complete chromosome diagrams; compare mitosis and meiosis; recognise meiosis in an unfamiliar life cycle; explain random fertilisation; use 2ⁿ

The specification says meiosis is needed “only in sufficient detail” to show these points. You do not need to learn the names of every sub-stage. The specification suggests examining meiosis in prepared slides of suitable plant or animal tissue; when you do, look for paired homologous chromosomes in meiosis I and the four small cells at the end.

Gene mutations

A gene mutation alters the order of bases in a section of DNA. Mutations can arise spontaneously during DNA replication, when a wrong base is occasionally inserted or a base is missed. Two types are named in the specification.

• Base substitution: one base is replaced by another. The number of bases stays the same.
• Base deletion: one base is lost. Every base after it moves up one place.

Effect of a substitution

A substitution changes one triplet. That triplet then codes for one of three outcomes: the same amino acid, a different amino acid, or a stop codon.

The genetic code is degenerate: several amino acids have two, four or even six different triplets. A substitution that turns one codon into another codon for the same amino acid changes nothing in the polypeptide. Such substitutions often involve the third base of a codon. A substitution that does change an amino acid alters the primary structure; this may alter the hydrogen and ionic bonding that folds the chain, so the tertiary structure and the function (for example an enzyme’s active site) can change. See the biological molecules guide for protein structure.

Effect of a deletion

Reading is in non-overlapping triplets, so a deletion shifts the reading frame. Every triplet from the deletion onwards is different (a frameshift). The polypeptide usually has many wrong amino acids, and a stop codon may appear early or late. This is why a deletion is normally more damaging than a substitution at the same position.

Worked example 1: translating a mutated sequence

You are given these data about the genetic code (you are not expected to recall codons): AUG Met, GAA and GAG Glu, CAU His, CAA Gln, UGG Trp, AAA Lys, UGA and UAA stop, AUU Ile, GGA Gly, AAU Asn.

The mRNA is AUG GAA CAU UGG AAA UAA.

Original polypeptide: Met-Glu-His-Trp-Lys, then stop.

1. GAA changes to GAG. Both code for Glu, so the polypeptide is unchanged. This is possible because the code is degenerate.
2. CAU changes to CAA. His becomes Gln, so one amino acid differs: Met-Glu-Gln-Trp-Lys.
3. UGG changes to UGA. This is a stop codon, so translation ends early: Met-Glu-His only.
4. The C of CAU is deleted. The sequence now reads AUG GAA AUU GGA AAU AA. Translation gives Met-Glu-Ile-Gly-Asn, so every amino acid after the second is wrong.

A deletion of three bases in a row keeps the frame in place, so only the amino acids from the lost triplet are affected. Check that you can say why.

Mutagenic agents

Mutations occur spontaneously at a low rate. Mutagenic agents increase that rate. Examples you may meet are ionising radiation, ultraviolet light and some chemicals. They do not decide which gene changes; they raise the chance of a change.

Worked example 2: mutation rate

A gene has 1500 bases. The data supplied give a spontaneous rate of 5 × 10⁻⁹ per base per DNA replication.

• Per replication: 1500 × 5 × 10⁻⁹ = 7.5 × 10⁻⁶ mutations in that gene.
• Over 4 × 10⁶ replications: 7.5 × 10⁻⁶ × 4 × 10⁶ = 30 mutations expected.

If a mutagenic agent raised the rate five-fold, the expected number would be 150.

Reading mutagen data

A bacterial strain cannot grow without an added amino acid. Colonies that grow on plates without it have mutated back. Three plates without a test chemical gave 18, 22 and 20 colonies (mean 20). Three plates with the chemical gave 86, 94 and 90 (mean 90). The percentage increase is (90 − 20) / 20 × 100 = 350%. This supports the idea that the chemical is mutagenic, but the claim would be stronger with more plates and a repeat.

Chromosome mutations: non-disjunction

Non-disjunction means that chromosomes fail to separate during meiosis. It arises spontaneously. The cells produced have too many or too few chromosomes.

• If the homologous pair fails to separate in meiosis I, both chromosomes of the pair go to one cell. After meiosis II, two gametes have one extra chromosome (n + 1) and two have one fewer (n − 1).
• If the sister chromatids fail to separate in meiosis II, one gamete is n + 1, one is n − 1 and two are normal.

Worked example 3: human chromosome number

A human gamete normally has 23 chromosomes. With non-disjunction of chromosome 21, one gamete has 24 and another has 22. Fertilisation by a normal gamete (23) gives a zygote with 24 + 23 = 47 chromosomes (three copies of chromosome 21, as in Down syndrome), or 22 + 23 = 45 chromosomes.

Meiosis

Meiosis happens in a diploid cell (2n), where chromosomes are in homologous pairs: one from each parent, with the same genes at the same loci but possibly different alleles. DNA is replicated once in interphase, so each chromosome has two identical chromatids. Then there are two nuclear divisions.

Stage	What happens	Result
Meiosis I	Homologous chromosomes pair up, then are separated	Two cells, each haploid (n); chromosomes still have two chromatids
Meiosis II	Chromatids are separated	Four cells, each haploid, with single-chromatid chromosomes

Meiosis produces four haploid daughter cells from one diploid parent cell, “usually” because in some life cycles (for example human egg production) some products do not survive.

Two sources of variation

Independent segregation of homologous chromosomes. In meiosis I each homologous pair lines up on the equator and the maternal and paternal chromosomes of every pair go to opposite poles. Which one goes to which pole is random for each pair, so the combination of maternal and paternal chromosomes in a gamete is different each time.

Crossing over. Early in meiosis I, homologous chromosomes pair and non-sister chromatids swap sections of DNA at points called chiasmata. The chromatids then carry new combinations of alleles, so chromatids that go into different gametes are no longer identical.

Worked example 4: crossing over

One chromosome of a homologous pair carries alleles A and B; its partner carries a and b.

• Without crossing over, the gametes are AB or ab only.
• A crossover between the two loci gives two recombinant chromatids, Ab and aB, as well as AB and ab. Four different gamete types are now possible.

The 2ⁿ calculation

Without crossing over, the number of different combinations of chromosomes in the gametes is 2ⁿ, where n is the number of homologous pairs. Each pair has two ways of going to a pole, and the pairs are independent, so you multiply two by itself n times.

Worked example 5: a species has 2n = 6, so n = 3 pairs. Let M be a maternal and P a paternal chromosome from each pair. The combinations are MMM, MMP, MPM, MPP, PMM, PMP, PPM and PPP, which is 2³ = 8.

For the human, n = 23: 2²³ = 8 388 608 gamete types from independent segregation alone.

Completing chromosome diagrams

Count in chromosomes and then in chromatids. Take a parent cell with 2n = 4: one long pair and one short pair.

Cell	Chromosomes	Chromatids per chromosome	Pairs?
Parent, after replication	4	2	Yes, two pairs
After meiosis I (each of 2 cells)	2 (one long, one short)	2	No
After meiosis II (each of 4 cells)	2 (one long, one short)	1	No

In a diagram, each cell after meiosis I must contain one member of every pair, never both. The chromosome number is halved at meiosis I, not meiosis II. DNA amount in arbitrary units: 2 before replication, 4 after, 2 per cell after meiosis I, 1 per cell after meiosis II.

Mitosis and meiosis compared

Feature	Mitosis	Meiosis
Divisions	One	Two
Daughter cells	Two	Four (usually)
Chromosome number	Stays the same	Halved
Genetic content	Identical to the parent and to each other	Different from the parent and from each other
Homologous pairs	Do not pair	Pair and cross over
Role	Growth, repair, asexual reproduction	Gamete or spore formation

Mitosis keeps identical DNA because chromatids separate once after replication and there is no pairing or crossing over.

Meiosis in life cycles

In animals, meiosis makes gametes. In an unfamiliar life cycle, find where chromosome number halves (2n to n): that is meiosis. Where it doubles (n to 2n), that is fertilisation. Mitosis is any step where the number stays the same.

Plants and some algae and fungi are different. In a moss or fern, a diploid plant makes haploid spores by meiosis. The spores grow by mitosis into a haploid plant, which makes gametes by mitosis, not meiosis. In some algae the zygote is the only diploid cell and divides by meiosis straight away. Never assume gametes come from meiosis.

Random fertilisation

Fertilisation involves a random male gamete and a random female gamete, which adds variation. If each parent can make 2ⁿ types, a zygote can be one of 2ⁿ × 2ⁿ = 2²ⁿ combinations (ignoring crossing over). For n = 3 that is 8 × 8 = 64. For humans it is 2⁴⁶ = 70 368 744 177 664, about 7.04 × 10¹³. Crossing over increases this further.

Common errors

• Saying meiosis II halves the chromosome number. It is meiosis I that does.
• Writing “chromosomes cross over” instead of non-sister chromatids of homologous chromosomes.
• Explaining a substitution as always harmful. Because of degeneracy it may change nothing.
• Using n as the diploid number in 2ⁿ. n is the number of homologous pairs.
• Treating gametes as the product of meiosis in every life cycle.

Official syllabus

AQA AS and A-level Biology specification (7401 and 7402), for first teaching 2015, section 3.4.3 (version 1.5), published by AQA.