Meiosis & Genetic Variation
Sexual reproduction requires a specialised cell division that halves the chromosome number — meiosis. Two rounds of division, with homologous chromosomes separating in the first and sister chromatids separating in the second, produce four genetically unique haploid cells. The uniqueness comes from two meiotic mechanisms — crossing over and independent assortment — that shuffle allele combinations between generations, providing the raw material on which natural selection acts.
Meiosis — stages & comparison with mitosis
Meiosis is the specialised cell division that produces haploid (n) gametes from diploid (2n) parent cells. Unlike mitosis (Topic 5), meiosis involves two successive divisions (meiosis I and meiosis II) and produces four genetically distinct daughter cells, each with half the chromosome number of the parent.
In sexual reproduction, two gametes fuse at fertilisation. Without meiosis, each gamete would carry the full diploid chromosome number, and the resulting zygote would be tetraploid (4n). After several generations, chromosome numbers would multiply catastrophically. Meiosis halves the chromosome number so that fertilisation restores the diploid number characteristic of the species.
Key terms before meiosis
A pair of chromosomes that carry the same genes in the same positions (loci), one inherited from each parent. They may carry the same or different alleles at each locus. In a diploid cell (e.g. human 2n=46), there are 23 homologous pairs.
The two identical copies of a chromosome joined at the centromere after DNA replication in S phase. A replicated chromosome consists of two sister chromatids. Non-sister chromatids are chromatids from homologous chromosomes.
The paired structure formed when homologous chromosomes come together in prophase I. Each bivalent consists of four chromatids (two pairs of sister chromatids). This pairing is called synapsis.
The point of physical contact between non-sister chromatids of homologous chromosomes during crossing over. Visible under the light microscope in late prophase I. Each chiasma represents a crossover event where segments are exchanged.
Meiosis I — the first division (reduction division)
Meiosis I separates homologous chromosomes. This is the reduction division — the chromosome number is halved. DNA replication has already occurred in S phase before meiosis begins.
Prophase I (the longest and most important stage):
- Chromosomes condense and become visible; nuclear envelope breaks down
- Homologous chromosomes come together (pair up) in a process called synapsis — forming bivalents
- Crossing over occurs: non-sister chromatids of homologous chromosomes break at corresponding points (chiasmata) and rejoin with the opposite chromosome, exchanging segments of DNA
- Each chiasma involves one crossover event; typically 1–3 chiasmata per bivalent
Metaphase I:
- Bivalents (pairs of homologous chromosomes) align on the metaphase plate
- Each homologous pair aligns randomly — the orientation of each bivalent is independent of all other bivalents: this is independent assortment
- Spindle fibres attach to the centromeres of each chromosome in the bivalent
Anaphase I:
- Homologous chromosomes are pulled to opposite poles of the cell by spindle fibres
- Each chromosome still consists of two sister chromatids joined at the centromere
- Centromeres do NOT split in anaphase I (contrast with mitosis/meiosis II)
Telophase I and cytokinesis:
- Two cells form, each with the haploid number of chromosomes (but each chromosome still has two chromatids)
- In many species, chromosomes partly decondense and a brief interphase-like period occurs; in others, cells proceed directly into meiosis II
- No further DNA replication occurs before meiosis II
Meiosis II — the second division
Meiosis II is similar to mitosis: it separates sister chromatids. It produces four haploid cells from the two haploid cells produced by meiosis I.
Prophase II: chromosomes condense (if they decondensed after meiosis I); new spindle forms; nuclear envelope breaks down
Metaphase II: chromosomes (each with two chromatids) align on the metaphase plate; spindle fibres attach to centromeres
Anaphase II: centromeres split; sister chromatids are pulled to opposite poles by spindle fibres
Telophase II and cytokinesis: four haploid daughter cells form; each cell contains one chromatid from each chromosome (now called a chromosome again); each cell is genetically unique
Meiosis vs mitosis — comparison
| Feature | Mitosis | Meiosis |
|---|---|---|
| Number of divisions | 1 | 2 (meiosis I + meiosis II) |
| Daughter cells produced | 2 | 4 |
| Ploidy of daughter cells | Diploid (2n) — same as parent | Haploid (n) — half parent |
| Genetic identity of daughters | Genetically identical to parent (barring mutation) | Genetically unique (crossing over + independent assortment) |
| Pairing of homologous chromosomes? | No | Yes — in prophase I (bivalent formation) |
| Crossing over? | No | Yes — in prophase I |
| Purpose | Growth, repair, asexual reproduction | Gamete production (sexual reproduction) |
| Where in humans? | All body (somatic) cells | Gonads only (testes and ovaries) |
During meiosis, when do homologous chromosomes first physically pair (synapse)?
- A. Metaphase I — when they align on the metaphase plate
- B. Prophase I — forming bivalents, and crossing over occurs between non-sister chromatids
- C. Anaphase I — just before being pulled to opposite poles
- D. Prophase II — before the second division
Sources of genetic variation
Sexual reproduction generates enormous genetic diversity in offspring. Three meiosis-related mechanisms, plus mutation, are the main sources of variation:
Crossing over (recombination)
Crossing over occurs during prophase I of meiosis. Non-sister chromatids of homologous chromosomes physically break at corresponding points, then rejoin with exchanged segments:
- Homologous chromosomes pair up (synapsis) in prophase I
- Non-sister chromatids (one from each homologue) break at corresponding positions — the break point is a chiasma
- The broken ends rejoin with the opposite chromatid, exchanging equal segments of DNA
- Result: new combinations of alleles on each chromatid — recombinant chromatids
Genetic effect: genes that were linked on the same chromosome (and would have been inherited together) are now separated onto different chromatids. This increases the number of different allele combinations possible in gametes beyond what independent assortment alone would produce.
The further apart two genes are on a chromosome, the more likely crossing over occurs between them (more chiasmata can form). Genes very close together (tightly linked) rarely recombine and tend to be inherited as a unit.
Independent assortment
Independent assortment occurs during metaphase I. When bivalents (pairs of homologous chromosomes) align at the metaphase plate, the orientation of each pair is random and independent of all other pairs:
For a species with n pairs of homologous chromosomes, there are 2n possible combinations of chromosomes in the gametes from independent assortment alone. In humans (n = 23): 223 = 8,388,608 ≈ 8.4 million different possible chromosome combinations.
Example with 3 chromosome pairs: if parental combinations are A•B•C (maternal) and a•b•c (paternal), independent assortment can produce gametes with combinations: ABC, ABc, AbC, Abc, aBC, aBc, abC, abc (8 = 23 combinations).
This is Mendel's law of independent assortment — it applies to genes on different chromosomes (unlinked genes). Linked genes on the same chromosome do NOT assort independently (but crossing over can partially overcome this).
Random fertilisation
Even if two parents each produced only one type of gamete, random fertilisation would still generate variation: any one of millions of sperm can fertilise any one of millions of eggs. Combining the gamete diversity from crossing over and independent assortment in both parents, the number of genetically distinct offspring possible approaches astronomical figures.
Mutation
Random mutations (point mutations, chromosome mutations) introduce new alleles and chromosomal rearrangements that are not present in either parent. Mutations are the ultimate source of new genetic variation — crossing over and independent assortment only reshuffle existing allele combinations. Without mutation, there would be no new alleles for selection to act upon.
- Crossing over: new allele combinations within chromosomes (prophase I)
- Independent assortment: new combinations of whole chromosomes (metaphase I)
- Random fertilisation: random combination of two genetically unique gametes
- Mutation: creation of new alleles (can occur at any time, not specific to meiosis)
Explain how crossing over and independent assortment each contribute to genetic variation in gametes. [6]
Crossing over [3 marks]
- Crossing over occurs during prophase I when homologous chromosomes pair (synapsis); non-sister chromatids break at chiasmata and rejoin with the opposite chromatid, exchanging segments of DNA [1]
- This creates new combinations of alleles (recombinant chromatids) that were not present in either parent chromosome [1]
- Genes that were previously linked on the same chromosome can now appear on separate chromatids, increasing the diversity of gametes produced [1]
Independent assortment [3 marks]
- During metaphase I, bivalents (pairs of homologous chromosomes) align randomly on the metaphase plate — the orientation of each pair is independent of all other pairs [1]
- This means maternal and paternal chromosomes are distributed randomly between the two cells of meiosis I — any combination of maternal and paternal chromosomes can end up in the same gamete [1]
- For a species with n pairs, 2n different chromosome combinations are possible; in humans (n=23), over 8 million different combinations can arise from independent assortment alone [1]
Linkage & sex-linked inheritance
Autosomal linkage
Genes on the same chromosome are said to be linked. Because they are physically on the same chromosome, they tend to be inherited together rather than independently — they violate Mendel's law of independent assortment. However, crossing over can separate linked genes.
Consider a dihybrid cross between parents AaBb × aabb (test cross) where A and B are on the same chromosome. If genes were unlinked, expected ratio among offspring: 1 AaBb : 1 Aabb : 1 aaBb : 1 aabb (1:1:1:1).
If genes are fully linked (no crossing over), only parental types appear: 1 AaBb : 1 aabb (all offspring have parental allele combinations).
In reality, genes are partially linked: parental types predominate, but recombinant types (Aabb and aaBb) also appear at lower frequency due to crossing over. The proportion of recombinants indicates how far apart the genes are on the chromosome.
If a dihybrid cross produces ratios that deviate from 9:3:3:1 (F₂ cross) or 1:1:1:1 (test cross) — specifically if parental combinations are more frequent and recombinant types are less frequent — linkage is indicated. A chi-squared test (Topic 16B) can confirm whether the deviation from expected independent assortment ratios is statistically significant.
Sex determination — sex chromosomes
In humans and many other animals, sex is determined by sex chromosomes:
Two copies of the X chromosome. Can be homozygous (XAXA) or heterozygous (XAXa) for X-linked genes. A heterozygous female is a carrier — she has one copy of a recessive allele but typically does not express the condition.
One X and one Y chromosome. The Y chromosome is much smaller than X and carries far fewer genes. Males have only one copy of X-linked genes — they are hemizygous for X-linked genes (only one allele, not two). Recessive X-linked alleles are always expressed in males.
Sex-linked inheritance
A sex-linked gene is one located on a sex chromosome. Most exam questions concern X-linked genes (genes on the X chromosome, with no corresponding allele on the Y). Classic examples: colour blindness, haemophilia, Duchenne muscular dystrophy.
Use superscripts on X to show alleles: XH = dominant allele; Xh = recessive allele. The Y chromosome is written as Y with no superscript (it does not carry the gene).
- XHXH = homozygous dominant female (unaffected, cannot be carrier)
- XHXh = heterozygous female (carrier; typically unaffected if H is dominant)
- XhXh = homozygous recessive female (affected)
- XHY = unaffected male
- XhY = affected male
Let XC = normal colour vision (dominant); Xc = colour blind (recessive).
Cross: carrier female XCXc × normal male XCY
| XC (from father) | Y (from father) | |
|---|---|---|
| XC (from mother) | XCXC normal female | XCY normal male |
| Xc (from mother) | XCXc carrier female | XcY colour-blind male |
Expected ratio: 1 normal female : 1 carrier female : 1 normal male : 1 colour-blind male
Key insight: colour blindness is more common in males because a single recessive allele on the X chromosome is sufficient to express the condition (males are hemizygous); females need two recessive alleles (homozygous XcXc) to be affected.
- Males have only one X chromosome — if it carries the recessive allele, the condition is expressed (no second X copy to "mask" it)
- Females have two X chromosomes — the recessive allele is usually masked by the dominant allele on the other X; females must be homozygous recessive to be affected
- Therefore, the frequency of affected males ≈ allele frequency; affected females = (allele frequency)²
- Example: if 8% of males are colour-blind (allele frequency q = 0.08), only q² = 0.0064 (0.64%) of females are affected
Haemophilia A is an X-linked recessive condition. A female who is a carrier (XHXh) has children with an unaffected male (XHY). What is the probability of their son having haemophilia?
- A. 0 (impossible)
- B. 25%
- C. 50%
- D. 100%
Gametes from mother: XH or Xh (equal probability)
Gametes from father: XH or Y (equal probability)
Sons receive Y from father and either XH or Xh from mother. So 50% of sons are XHY (unaffected) and 50% are XhY (haemophilia). Overall, 25% of all children (50% of sons) have haemophilia.
In a dihybrid test cross (AaBb × aabb), a student observes the following offspring: 480 AaBb, 20 Aabb, 18 aaBb, 482 aabb. Total = 1000.
(a) Explain what the results suggest about the relationship between genes A and B. [2]
(b) Explain the origin of the Aabb and aaBb offspring. [2]
(c) Describe how a chi-squared test could be used to confirm the student’s explanation. [2]
(a) Linkage evidence [2 marks]
- The parental combinations (AaBb and aabb) are far more frequent (480+482 = 962 out of 1000) than the recombinant types (Aabb and aaBb, only 38 out of 1000) — indicating that A and B are linked (on the same chromosome) [1]
- If A and B were unlinked (on different chromosomes), independent assortment would predict approximately equal numbers of all four offspring types (1:1:1:1, i.e. ~250 each); the observed ratio strongly deviates from this [1]
(b) Origin of recombinants [2 marks]
- The Aabb and aaBb offspring are recombinant types — they carry allele combinations not present in either parent [1]
- These arise from crossing over between the two gene loci during prophase I of meiosis in the AaBb parent; a chiasma forms between the A/a and B/b loci, and non-sister chromatids exchange segments, placing A with b and a with B on recombinant chromatids [1]
(c) Chi-squared test [2 marks]
- Use the expected 1:1:1:1 ratio under the null hypothesis that the genes are unlinked; calculate expected numbers: 250 each; then calculate χ² = ∑(O−E)²/E [1]
- Compare χ² to the critical value at appropriate degrees of freedom (3) and p = 0.05; if χ² exceeds the critical value, the difference is statistically significant and the null hypothesis (no linkage) is rejected [1]
Topic 16A Practice — Comprehensive
Mixed practice covering meiosis, genetic variation, linkage, and sex-linked inheritance.
Which event occurs in anaphase I of meiosis but NOT in anaphase II?
- A. Sister chromatids separate and move to opposite poles
- B. Homologous chromosomes (each still as two chromatids) separate and move to opposite poles
- C. Centromeres split
- D. Chromosomes condense and become visible
Two genes are located on different chromosomes. Which principle explains why offspring can inherit any combination of alleles from these two genes?
- A. Crossing over between non-sister chromatids
- B. Independent assortment of bivalents at metaphase I
- C. Random fusion of gametes at fertilisation
- D. Mutation occurring in S phase before meiosis
Meiosis and mitosis both involve cell division but differ in several important ways.
(a) State THREE ways in which meiosis differs from mitosis. [3]
(b) Describe what happens to chromosomes during prophase I of meiosis that does NOT occur in prophase of mitosis. [3]
(c) Explain why meiosis, but not mitosis, produces genetically unique daughter cells. [2]
(a) Three differences [3 marks; any 3]
- Meiosis involves 2 divisions; mitosis involves 1 division [1]
- Meiosis produces 4 daughter cells; mitosis produces 2 [1]
- Meiosis produces haploid (n) cells; mitosis produces diploid (2n) cells [1]
- Meiosis produces genetically unique cells; mitosis produces genetically identical cells [1]
- Homologous chromosomes pair (synapsis/bivalents) in meiosis I; this does not occur in mitosis [1]
- Crossing over occurs in meiosis (prophase I); does not occur in mitosis [1]
(b) Prophase I events not in mitosis prophase [3 marks]
- Homologous chromosomes pair up (synapsis) to form bivalents [1]
- Crossing over occurs: non-sister chromatids of homologous chromosomes break and exchange segments at chiasmata [1]
- This produces recombinant chromatids with new allele combinations not present in either parent chromosome [1]
(c) Why meiosis produces genetically unique cells [2 marks]
- Crossing over (prophase I) creates new allele combinations within chromosomes; independent assortment (metaphase I) means random combinations of maternal and paternal chromosomes end up in each gamete [1]
- In mitosis, chromosomes replicate and are distributed equally without any shuffling — each daughter cell receives identical copies of every chromosome, so all daughters are genetically identical to the parent [1]
Red–green colour blindness is caused by a recessive allele (Xc) on the X chromosome. A woman with normal vision whose father was colour-blind marries a man with normal vision.
(a) State the genotype of the woman. Explain your reasoning. [2]
(b) Construct a genetic diagram to determine the expected ratio of phenotypes among their offspring. [4]
(c) State why colour blindness is more common in males than females. [1]
(a) Woman's genotype [2 marks]
- Genotype: XCXc (carrier) [1]
- Her father was colour-blind (XcY); she must have inherited his Xc chromosome. She herself has normal vision, so her other X must carry the dominant allele XC (inherited from her mother) [1]
(b) Genetic diagram [4 marks]
Parents: XCXc (mother) × XCY (father)
Gametes: XC, Xc from mother; XC, Y from father
| XC | Y | |
|---|---|---|
| XC | XCXC | XCY |
| Xc | XCXc | XcY |
Expected offspring: [1 for correct Punnett / 1 for genotypes / 1 for phenotypes / 1 for ratio]
- XCXC — normal-vision female (25%)
- XCXc — carrier female, normal vision (25%)
- XCY — normal-vision male (25%)
- XcY — colour-blind male (25%)
Ratio: 3 normal vision : 1 colour-blind (or 2 normal female : 1 normal male : 1 colour-blind male)
(c) Why more common in males [1 mark]
- Males are hemizygous for X-linked genes — they have only one X chromosome, so any recessive allele (Xc) on that X chromosome is expressed with no dominant allele to mask it; females require two copies of the recessive allele to be affected [1]
Topic 16A — Common Mistakes
- 📓Saying crossing over occurs in metaphase ICrossing over occurs in prophase I, not metaphase I. Metaphase I is when bivalents align on the metaphase plate — by this stage, crossing over has already happened and chiasmata are visible holding the bivalents together. Independent assortment (random alignment) occurs at metaphase I.
- 📒Saying centromeres split in anaphase ICentromeres do NOT split in anaphase I. In anaphase I, whole chromosomes (each still two sister chromatids) move to opposite poles — the homologous pair is separated. Centromere splitting happens in anaphase II (like mitosis), when sister chromatids finally separate.
- 📊Confusing "independent assortment" and "crossing over"Independent assortment = random orientation of bivalents at metaphase I → different combinations of whole chromosomes in gametes. Crossing over = physical exchange of DNA segments between non-sister chromatids in prophase I → new allele combinations within chromosomes. Both increase variation but by different mechanisms. Independent assortment only helps genes on different chromosomes; crossing over helps genes on the same chromosome.
- 📋Writing sex-linked genotypes without the X superscript notationIn sex-linked genetics, always write alleles as superscripts on the X chromosome: XHXh (carrier female), XhY (affected male). Just writing "Hh" or "HY" is wrong and loses marks — it doesn't distinguish autosomal from sex-linked inheritance.
- 💥Saying females cannot be affected by X-linked recessive conditionsFemales CAN be affected — they need to be homozygous recessive (XhXh). This happens when a carrier mother and an affected father have daughters. It's uncommon, not impossible. This error typically appears when students say "only males are affected" without qualification.
- 👤Confusing "carrier" and "affected" in sex-linked geneticsA carrier female (XHXh) has one dominant and one recessive allele — she is typically unaffected but can pass the recessive allele to her sons. "Carrier" applies specifically to heterozygous females in X-linked recessive genetics. Males cannot be carriers — they are either affected (XhY) or not (XHY). Males are hemizygous, not heterozygous.
- 🔍Confusing "linked genes" with "genes at the same locus"Linked genes are on the same chromosome but at different loci. Two alleles of the same gene are at the same locus on homologous chromosomes — they are alleles, not linked genes. Linkage refers to two different genes residing on the same chromosome.
- 📓Saying meiosis produces "clones" or "identical" cellsMitosis produces genetically identical daughter cells (clones). Meiosis produces four genetically unique cells due to crossing over and independent assortment. Saying "meiosis produces identical haploid cells" is a fundamental error.
- 👥Forgetting that males are hemizygous (not homozygous or heterozygous)Males have only one allele for X-linked genes — they are hemizygous. Using the terms "homozygous" or "heterozygous" for males at X-linked loci is incorrect. Always use "hemizygous" when describing males in X-linked genetics questions.
Topic 16A is concept-heavy with multiple connections to genetics problems in 16B. Highest-yield items: meiosis I stages with crossing over (prophase I) and independent assortment (metaphase I), meiosis II separates sister chromatids (centromeres split), 8-row meiosis vs mitosis comparison table, crossing over = new allele combinations within chromosomes (prophase I), independent assortment = random chromosome combinations between cells (metaphase I), 2n combinations formula, detecting linkage from skewed offspring ratios (parental types >> recombinants), sex-linked genotype notation XAXa / XaY, why X-linked recessive conditions are more common in males (hemizygous), carrier female vs affected female distinction. Synoptic links: Topic 5 (mitotic cell cycle comparison), Topic 6 (genes, alleles, loci), Topic 17 (natural selection acts on genetic variation), Topic 16B (chi-squared test, Punnett squares).