Why Some Genes Refuse to Separate During Meiosis

Following one trait at a time reveals dominance and segregation. Following two traits at once reveals something new: genes on different chromosomes are shuffled independently, while genes on the same chromosome tend to travel together.

This part covers the dihybrid cross, the chromosomal theory of inheritance, linkage and recombination, and polygenic inheritance and pleiotropy.

**A dihybrid cross follows two traits at once; the Law of Independent Assortment says that when two pairs of traits are combined in a hybrid, one pair segregates independently of the other, so an RrYy plant makes four kinds of gametes in equal numbers and its F${}_2$ shows a 9 : 3 : 3 : 1 phenotypic ratio.

The cross:

- Parents — round yellow seeds (RRYY) × wrinkled green seeds (rryy)
- F${}_1$ — all round yellow (RrYy)
- F${}_1$ gametes — RY, Ry, rY and ry, in equal proportions

The F${}_2$, from 16 equally likely combinations:

- 9 round yellow
- 3 round green
- 3 wrinkled yellow
- 1 wrinkled green

Why 9 : 3 : 3 : 1.** Each trait alone gives 3 : 1, and because the two assort independently the ratios multiply:

$$(3:1)\times (3:1)=9:3:3:1$$

Worked example. For $320$ F${}_2$ seeds:

$$\frac{9}{16}\times 320=180,\frac{3}{16}\times 320=60,\frac{1}{16}\times 320=20$$

so we expect $180$ round yellow, $60$ round green, $60$ wrinkled yellow and $20$ wrinkled green seeds.

An everyday example. Plant breeders combine disease resistance from one wheat variety with high yield from another, relying on the genes assorting independently.

The substance. Independent assortment holds for genes on different chromosomes — genes close together on one chromosome break the rule, as linkage shows.

The chromosomal theory of inheritance of Sutton and Boveri states that genes are carried on chromosomes, and that the pairing and separation of chromosomes during meiosis account for the laws of segregation and independent assortment.

The parallel behaviour:

- Both occur in pairs — alleles of a gene, and homologous chromosomes
- Both segregate during gamete formation — alleles separate, and homologous chromosomes separate in meiosis I
- Each gamete receives one of each pair — one allele, and one chromosome of each homologous pair
- Pairs act independently — one gene pair segregates independently of another, and each homologous pair lines up independently of the others at metaphase I

Worked example. A cell with $3$ pairs of homologous chromosomes can produce $2^3=8$ genetically different kinds of gametes from independent assortment alone. With $23$ pairs, as in humans, the number is $2^{23}$, more than $8$ million.

An everyday example. Brothers and sisters from the same parents look different partly because each gamete receives a different mix of chromosomes.

The substance. The theory links an abstract rule to a visible process — the separation of chromosomes, which can be watched under a microscope.

**Morgan's dihybrid crosses in Drosophila showed that genes on the same X chromosome did not assort independently — most offspring kept the parental combinations, showing linkage, while fewer showed new combinations, showing recombination — and the frequency of recombination between two genes is used as a measure of their distance to build genetic maps.

Linkage and recombination:

- Linkage — the physical association of genes on a chromosome
- Recombination — the appearance of non-parental gene combinations, produced by crossing over during meiosis
- Tightly linked genes, such as those for yellow body and white eye, show very little recombination; loosely linked genes, such as white eye and miniature wing, show much more

Genetic maps. The recombination frequency between gene pairs on the same chromosome is used to work out their relative positions.

Worked example.** In a test cross, $1000$ offspring include $860$ with parental combinations and $140$ recombinants:

$$\text{recombination frequency}=\frac{140}{1000}\times 100=14\text{ percent}$$

so the genes are about 14 map units apart. A third gene $5$ units from the first and $9$ from the second must lie between them, because $5+9=14$.

An everyday example. Genetic testing laboratories use chromosome maps to locate genes linked to inherited diseases.

The substance. Recombination frequency rises with distance — genes far apart are more likely to be separated by crossing over.

Polygenic traits are controlled by three or more genes, each adding a small effect, so they show a continuous range of phenotypes, as in human skin colour; pleiotropy is when one gene affects several phenotypic traits, as in phenylketonuria.

Polygenic inheritance:

- Several genes contribute additively to one trait
- The environment also influences the phenotype
- Phenotypes form a continuous gradation instead of a few distinct classes
- Examples: human height and skin colour

Skin colour model. Suppose three genes A, B and C each have a dominant allele adding dark pigment. AABBCC is darkest and aabbcc lightest, while genotypes with the same number of dominant alleles, such as AaBbCc and AABbcc, give the same intermediate shade.

Pleiotropy:

- A single gene produces multiple phenotypic effects
- Usually because it affects a metabolic pathway that influences many processes
- Phenylketonuria — a mutation in the gene for the enzyme phenylalanine hydroxylase lets phenylalanine build up, causing intellectual disability and reduced hair and skin pigmentation

An everyday example. Children in one family often show a range of heights and skin shades, because many genes, along with diet and sunlight, shape these traits.

The substance. Polygenic means many genes for one trait; pleiotropic means one gene for many traits — the two are opposites.