Epistasis

Mendelian ratios assume that each gene acts independently of the others. In reality, many phenotypes are the result of several genes acting together, and sometimes the alleles at one locus mask or modify the expression of alleles at another. This phenomenon is called epistasis, and it is a major reason why dihybrid ratios in nature often deviate from the classic 9:3:3:1. OCR A-Level Biology A specification module 6.1.2(e) requires you to understand epistasis and to work out modified phenotypic ratios in dihybrid crosses.

Key Definitions:

• Epistasis — the interaction of different genes at different loci where one gene (the epistatic gene) masks or modifies the effect of another (the hypostatic gene).
• Recessive epistasis — masking occurs only when the epistatic gene is homozygous recessive. Modified ratio: 9 : 3 : 4.
• Dominant epistasis — masking occurs in the presence of even one dominant allele at the epistatic locus. Modified ratio: 12 : 3 : 1.
• Complementary epistasis — two genes must both be expressed for a phenotype to appear. Modified ratio: 9 : 7.

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Why Mendelian Ratios Break Down

A dihybrid cross between two heterozygotes (AaBb × AaBb) should give a 9:3:3:1 phenotypic ratio, as the Punnett square below shows:

	AB	Ab	aB	ab
AB	AABB	AABb	AaBB	AaBb
Ab	AABb	AAbb	AaBb	Aabb
aB	AaBB	AaBb	aaBB	aaBb
ab	AaBb	Aabb	aaBb	aabb

Sixteen equally likely outcomes group into:

• 9 A_B_ (at least one dominant at each locus)
• 3 A_bb (dominant at A, recessive at B)
• 3 aaB_ (recessive at A, dominant at B)
• 1 aabb (recessive at both)

Epistasis combines some of these classes together, because the visible phenotypes overlap.

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Recessive Epistasis (9:3:4)

When the homozygous recessive genotype at one locus masks the phenotype at the other.

Coat colour in mice (the agouti example)

Mouse coat colour depends on two genes:

• Gene C — if cc, no pigment is produced at all → albino, regardless of the other gene.
• Gene A — in a pigmented mouse (C_), A_ gives agouti (brown with dark tips); aa gives black.

The cc genotype is epistatic to the agouti/black gene — it blocks the earlier step in the pigment pathway. A cc mouse cannot make any pigment at all, so whatever alleles it has at the A locus are irrelevant.

Cross two dihybrid mice CcAa × CcAa:

• 9 C_A_ — agouti
• 3 C_aa — black
• 3 ccA_ — albino (cannot make pigment)
• 1 ccaa — albino (cannot make pigment)

The two albino classes merge: 9 agouti : 3 black : 4 albino — the classic 9:3:4 recessive epistasis ratio.

flowchart LR
    CCAA[CcAa x CcAa] --> P1[9 agouti]
    CCAA --> P2[3 black]
    CCAA --> P3[3 albino cc A_]
    CCAA --> P4[1 albino cc aa]
    P3 --> M[Merged 4 albino]
    P4 --> M

Why the merging makes biological sense

The two genes act sequentially in a biochemical pathway. Gene C catalyses the first step — without a functional C enzyme, no pigment precursor is made, and gene A has nothing to modify. Blocking an early step makes later steps irrelevant: that is the essence of recessive epistasis.

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Dominant Epistasis (12:3:1)

When a single dominant allele at one locus masks the phenotype at the other.

Squash fruit colour

In summer squash, colour depends on two genes:

• Gene W — W_ (dominant) gives white fruit, regardless of the other gene.
• Gene Y — in ww squash, Y_ gives yellow and yy gives green.

Gene W is dominant-epistatic: its dominant allele produces an inhibitor of pigment production, so W_ squash are white no matter what alleles they have at the Y locus.

Cross two dihybrids WwYy × WwYy:

• 9 W_Y_ — white
• 3 W_yy — white
• 3 wwY_ — yellow
• 1 wwyy — green

The two "W_" classes merge: 12 white : 3 yellow : 1 green — the classic 12:3:1 dominant epistasis ratio.

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