Genetic diversity can arise as a result of mutation or during meiosis

In a nutshell

Every individual in a species is genetically slightly different, and this subtopic is about where that variation comes from.

New variation has two sources: mutation, which creates brand-new alleles by changing the DNA base sequence, and meiosis plus random fertilisation, which shuffle existing alleles into new combinations in the gametes and the zygote.

That variation matters because it is the raw material natural selection acts on.

Assumed knowledge: DNA, genes and chromosomes, DNA and protein synthesis.

Core content

Gene mutations

A gene mutation is a change in the base sequence of DNA.

Mutations happen spontaneously, most often as random errors during DNA replication. A mutation in a gene can create a new allele of that gene.

The two changes you must know are substitution and deletion (an addition, or insertion, of a base is examined too and behaves like a deletion).

Why a substitution often changes nothing

The genetic code is degenerate: more than one base triplet codes for the same amino acid.

So when a base is substituted, the new triplet may still code for the same amino acid. This is why not all base substitutions change the sequence of encoded amino acids, and the protein is unaffected.

If the new triplet does code for a different amino acid, only that one amino acid in the polypeptide is changed.

Frameshift: why deletion and addition are worse

The bases are read in non-overlapping triplets from a fixed starting point. Remove one base or add one base, and everything after it shifts along by one, so every triplet from the mutation onwards is different.

That usually changes many amino acids, so the polypeptide's primary structure is badly altered and the protein is very likely non-functional.

Still don't get it? · frameshift

Imagine a sentence written with no spaces, read three letters at a time: THE·CAT·SAT. You know where each word starts only by counting in threes from the beginning.

Now delete the very first letter. You are left with HEC·ATS·AT..., and every single "word" after the cut is now gibberish, not just the one you touched. Adding a letter does the same thing: everything shifts along by one and the reading frame is wrong from that point on.

A substitution is different. Swap the T in CAT for an R and you get CAR: one word changes, the rest are untouched.

Exam version: the bases are read in fixed triplets. A deletion or an addition of a base shifts the reading frame, so all following triplets, and therefore many amino acids, are changed. A substitution alters at most one triplet, so at most one amino acid, and because the code is degenerate it may change none at all.

There is one neat consequence: if a multiple of three bases is deleted or added, the reading frame is not shifted, because whole triplets are removed or inserted and the triplets after them still line up.

Mutagenic agents

Mutations happen at a low natural rate, but mutagenic agents increase the rate of gene mutation.

You must be able to name specific ones:

• Ultraviolet (UV) light
• Ionising radiation, for example X-rays and gamma rays
• Chemical mutagens, for example benzene and the tar in tobacco smoke

Chromosome mutations: non-disjunction

Not all mutations change the base sequence. A mutation can change the number of chromosomes in a cell instead.

These arise spontaneously by non-disjunction during meiosis: the chromosomes fail to separate (homologous chromosomes in the first division, or sister chromatids in the second).

As a result, a gamete ends up with one more or one fewer chromosome than normal. If that gamete is fertilised, the offspring has an abnormal chromosome number. Having three copies of chromosome 21 (Down's syndrome) is a familiar example.

Meiosis: two divisions, four haploid cells

Meiosis is the cell division that makes gametes. Two nuclear divisions produce four haploid daughter cells from a single diploid parent cell.

• Meiosis I separates the homologous chromosomes. This is the division that halves the chromosome number, taking the cell from diploid (2n) to haploid (n).
• Meiosis II separates the sister chromatids (like mitosis does), giving four cells in total.

You are only expected to know meiosis in enough detail to explain these outcomes, not to recite the named stages.

Spec skill: given the chromosome content of the parent cell, you should be able to draw the chromosome content of the cells after the first and the second meiotic division. After meiosis I each cell has half the number of chromosomes, but each chromosome is still two sister chromatids. After meiosis II each cell has that same halved number, now as single chromosomes.

Mitosis and meiosis: the different outcomes

How meiosis creates genetic variation

Meiosis makes the four daughter cells genetically different from one another through two processes.

1. Independent segregation of homologous chromosomes. The homologous pairs line up randomly, so which chromosome of each pair (maternal or paternal) ends up in a given cell is independent of every other pair. Independent segregation produces new combinations of maternal and paternal chromosomes.

2. Crossing over. Where homologous chromosomes pair up, the non-sister chromatids exchange sections. The exchange happens at points called chiasmata. Because the swapped sections carry different alleles, crossing over produces new combinations of alleles on the chromatids.

Still don't get it? · independent segregation

Picture two coins on the table, a 1p and a 2p, and you flip both. The 1p can land heads or tails, and, completely separately, so can the 2p. Neither coin cares what the other did. Two independent coins give four equally likely outcomes: HH, HT, TH, TT.

Now swap the coins for your two pairs of chromosomes. Each pair has a "maternal side" and a "paternal side", and when the pairs line up in meiosis, each pair decides which side goes which way independently of the other pair. Two pairs, four possible gametes, exactly like the coins.

Add more pairs and you multiply: three pairs give 2 x 2 x 2 = 8, and n pairs give 2 to the power n. That is where the formula comes from.

Exam version: because homologous pairs undergo independent segregation, the gametes carry new combinations of maternal and paternal chromosomes, and the number of possible combinations from this alone is $2^n$, where n is the number of homologous pairs.

Counting the combinations (maths skill)

The number of different chromosome combinations in the gametes from independent segregation alone (ignoring crossing over) is:

$\text{combinations} = 2^{n}$

where n is the number of homologous pairs in the diploid parent cell.

Random fertilisation then multiplies the variation again: because any male gamete can fuse with any female gamete, the number of possible chromosome combinations in the zygote is:

$(2^{n}) \times (2^{n}) = 2^{2n}$

Random fertilisation

Fertilisation is random: any one of the genetically different male gametes can fuse with any one of the genetically different female gametes.

This combines two random sets of chromosomes, so it further increases genetic variation within a species, producing a zygote with a genetic makeup different from both parents and from any sibling.

Recognising meiosis in an unfamiliar life cycle

You may be given a life cycle you have never seen and asked where meiosis happens. Use two rules:

• Meiosis is wherever the chromosome number is halved, that is a diploid cell (2n) gives rise to haploid cells (n). It does not have to make gametes directly.
• Fertilisation is wherever two haploid cells fuse to restore the diploid number (n + n gives 2n).

Any other division, where the chromosome number stays the same, is mitosis.

Worked examples

1. Calculation: possible chromosome combinations.

A plant species has 4 pairs of homologous chromosomes (n = 4). Then a human (n = 23) for comparison.

Combinations in the gametes from independent segregation alone:

$2^{n} = 2^{4} = 16$

For a human, n = 23, so each person can make:

$2^{23} = 8\,388\,608 \text{ chromosome combinations}$

Combinations in the zygote after random fertilisation (any gamete with any gamete):

$(2^{23}) \times (2^{23}) = 2^{46} \approx 7.0 \times 10^{13}$

So random fertilisation of human gametes can produce over 70 trillion chromosome combinations, and that is before crossing over is taken into account, which makes the true figure far higher.

2. Model 5-mark answer: "Explain how meiosis and fertilisation produce genetic variation."

A full answer needs five distinct, linked points, and must name both meiotic processes plus fertilisation:

1. Independent segregation of homologous chromosomes;
2. produces new combinations of maternal and paternal chromosomes (in the gametes);
3. crossing over between non-sister chromatids of homologous chromosomes;
4. produces new combinations of alleles;
5. random fertilisation of gametes combines the chromosomes of two genetically different gametes, increasing variation further.

Common exam mistakes

• Saying meiosis II halves the chromosome number. The number is halved at meiosis I, when the homologous chromosomes separate; meiosis II separates sister chromatids.
• Confusing the two variation processes. Crossing over gives new combinations of alleles; independent segregation gives new combinations of maternal and paternal chromosomes. Examiners see these swapped constantly.
• Saying crossing over happens between "any two chromosomes" or between sister chromatids. It is between non-sister chromatids of homologous chromosomes.
• Writing that crossing over or mutation "makes new genes". Crossing over makes new combinations of alleles; a gene mutation makes a new allele, not a new gene.
• Describing a chromosome-number mutation as a "change in the base sequence". Non-disjunction changes the number of chromosomes, not the sequence of bases.
• Giving vague mutagens. "Radiation", "chemicals" and "smoking" are not credited; name UV light, X-rays / gamma rays, or a named chemical such as benzene or tar in tobacco smoke.
• Forgetting the degenerate code. Marks are lost by claiming every substitution changes the protein; because the code is degenerate, a substitution may code for the same amino acid.
• Mixing up haploid and diploid. Haploid (n) = one of each chromosome; diploid (2n) = chromosomes in homologous pairs. Examiner reports repeatedly flag confusion of these two terms.
• Drawing daughter cells from scratch instead of from the parent cell given. When completing a meiosis diagram, start from the chromosomes shown in the parent cell in the question.

Key definitions

• Gene mutation: a change in the base sequence of DNA.
• Substitution: a mutation in which one base is replaced by a different base.
• Deletion: a mutation in which one base is removed from the sequence.
• Frameshift: a shift in the reading frame caused by a deletion or addition of a base, changing every triplet (and so every amino acid) from the point of the mutation onwards.
• Degenerate (genetic code): more than one base triplet codes for the same amino acid.
• Mutagenic agent: a factor that increases the rate of gene mutation.
• Non-disjunction: the failure of homologous chromosomes (or sister chromatids) to separate during meiosis, producing cells with one more or one fewer chromosome.
• Meiosis: a form of nuclear division that produces four haploid daughter cells from a single diploid parent cell.
• Haploid (n): a cell or nucleus containing one of each chromosome (a single set).
• Diploid (2n): a cell or nucleus containing chromosomes in homologous pairs (two sets).
• Homologous chromosomes: a pair of chromosomes, one maternal and one paternal, that carry the same genes at the same loci but may carry different alleles.
• Independent segregation: the random separation of homologous chromosomes into daughter cells in meiosis, producing new combinations of maternal and paternal chromosomes.
• Crossing over: the exchange of sections, and therefore of alleles, between the non-sister chromatids of homologous chromosomes.
• Random fertilisation: the fusion of any male gamete with any female gamete, combining two genetically different sets of chromosomes.

Specification

• I can state that a gene mutation is a change in the base sequence of DNA and can arise spontaneously during DNA replication.
• I can describe base substitution and base deletion (and addition), and explain why a deletion or addition causes a frameshift.
• I can explain, using the degenerate nature of the genetic code, why not all base substitutions change the sequence of encoded amino acids.
• I can state that mutagenic agents increase the rate of gene mutation, and name examples.
• I can explain that mutations in the number of chromosomes can arise spontaneously by non-disjunction during meiosis.
• I can explain how two nuclear divisions in meiosis produce four haploid daughter cells from one diploid parent cell.
• I can explain how independent segregation of homologous chromosomes produces genetically different daughter cells.
• I can explain how crossing over between homologous chromosomes produces further genetic variation.
• I can complete diagrams showing the chromosome content of cells after the first and second meiotic divisions, given the parent cell.
• I can explain the different outcomes of mitosis and meiosis.
• I can recognise where meiosis occurs when given an unfamiliar life cycle.
• I can use $2^n$ and $2^{2n}$ to calculate the number of chromosome combinations after meiosis and after random fertilisation.

Related notes

• DNA, genes and chromosomes
• DNA and protein synthesis
• Genetic diversity and adaptation