Unit 2: Alleles, Gene Interactions and Cytoplasmic Inheritance

I. Orientation: Beyond Simple Mendelian Ratios

Mendel's laws assume two alleles per gene, complete dominance, and independent nuclear genes with a one-to-one gene–trait relationship. This unit examines the many exceptions where these assumptions break down—at the level of allele number and behaviour, of genes modifying one another, and of genes inherited outside the nucleus.

• Allele: an alternative form of a gene at a given locus; a diploid carries two, one per homologue.
• Gene interaction: the modification of one gene's phenotypic expression by another gene at a different locus, altering expected dihybrid ratios (from 9:3:3:1).
• Wild type vs. mutant: the most common natural allele (denoted +) is the reference against which variants are scored.
• Cytoplasmic (extranuclear) inheritance: transmission of traits by DNA in mitochondria and plastids, following non-Mendelian, usually maternal, patterns.

II. Alleles and Allelic Relationships

Alleles differ in number available in a population and in how a heterozygote's two alleles jointly produce a phenotype.

A. Multiple Alleles

More than two alleles for one gene exist in a population, though any individual still carries only two.

• Definition: three or more allelic forms of a single locus arising by repeated mutation.
• ABO blood group: the I gene has alleles Iᴬ, Iᴮ, i. Iᴬ and Iᴮ encode transferase enzymes adding N-acetylgalactosamine or galactose to the H antigen; i is null.
  • Genotype–phenotype: IᴬIᴬ/Iᴬi → A; IᴮIᴮ/Iᴮi → B; IᴬIᴮ → AB; ii → O.
• Population count: for n alleles, the number of possible genotypes is n(n+1)/2; for ABO (n=3) this gives 6 genotypes yielding 4 phenotypes.

B. Incomplete Dominance and Codominance

In heterozygotes the two alleles may blend or both express fully—two distinct outcomes.

1. Incomplete dominance: heterozygote is intermediate; neither allele is fully dominant.
   • Example: Mirabilis jalapa flowers—RR red × rr white → Rr pink. F₂ ratio is 1 red : 2 pink : 1 white (phenotype = genotype ratio).
   • Basis: one functional allele produces insufficient pigment for the full red phenotype (dosage effect).
2. Codominance: both alleles expressed fully and simultaneously in the heterozygote.
   • Example: blood group AB—IᴬIᴮ displays both A and B antigens on erythrocytes, not an intermediate.
   • Contrast: incomplete dominance mixes into one new phenotype; codominance shows both parental phenotypes distinctly.

C. Allelic Series

Multiple alleles of one gene can be ranked by their dominance relationships.

• Definition: an ordered set of alleles arranged by relative dominance, called a dominance hierarchy.
• Coat colour in rabbits (C locus): C (full) > c^ch (chinchilla) > c^h (Himalayan) > c (albino).
  • Reading the series: Cc = full colour; c^h c = Himalayan; cc = albino.
• Note: relationships need not be strictly linear—some pairs within a series show codominance or incomplete dominance.

III. Gene Interactions

Two or more genes jointly determine a single character; interaction reshapes dihybrid ratios and complicates the gene–phenotype map.

A. Epistasis and Types

Epistasis is the masking of one gene's (hypostatic) expression by an allele at a second (epistatic) locus.

• Recessive epistasis (9:3:4): homozygous recessive at one locus masks the other. Labrador coat—ee yields yellow regardless of the black/brown B locus.
• Dominant epistasis (12:3:1): a dominant allele masks the second locus. Summer squash—W_ gives white fruit whatever the colour gene.
• Duplicate recessive / complementary genes (9:7): dominant alleles at both loci needed for the trait. Sweet pea—C_P_ purple; all others white.
• Duplicate dominant genes (15:1): a dominant at either locus suffices. Shepherd's purse seed-capsule shape.
• Dominant + recessive (13:3): a dominant at one locus and recessive at another both suppress. Certain fowl plumage colour.

Classic dihybrid:                9 : 3 : 3 : 1
Recessive epistasis:             9 : 3 : 4
Dominant epistasis:              12 : 3 : 1
Complementary (dup. recessive):  9 : 7
Duplicate dominant:              15 : 1
Dominant & recessive:            13 : 3

B. Pleiotropy

One gene influences multiple, seemingly unrelated phenotypic traits.

• Definition: a single gene affecting two or more distinct characters, usually because one protein acts in several pathways.
• Sickle-cell anemia: the HbS allele (Glu→Val at position 6 of β-globin) causes anemia, pain crises, spleen damage and malaria resistance—all from one substitution.
• Contrast with epistasis: pleiotropy is one gene → many traits; epistasis is many genes → one trait.

C. Genomic Imprinting

The phenotype of an allele depends on the parent from which it was inherited.

• Definition: differential expression of a gene based on parental origin, set by epigenetic DNA methylation of one parental copy.
• Mechanism: the imprinted (methylated) allele is silenced; only the copy from the non-imprinting parent is expressed.
• Prader–Willi vs. Angelman: both from a 15q11–13 defect—loss of the paternal copy gives Prader–Willi; loss of the maternal copy gives Angelman.
• Reversibility: imprints are erased and reset in the germ line each generation, so the same DNA can carry opposite marks in son vs. daughter.

D. Penetrance

Penetrance measures how reliably a genotype produces its expected phenotype in a population.

• Definition: the percentage of individuals with a given genotype who show the associated phenotype.
• Complete penetrance: 100% of carriers express the trait (e.g. Huntington's disease alleles typically).
• Incomplete penetrance: fewer than 100% express it—e.g. polydactyly alleles may show ~70% penetrance, so unaffected carriers exist.
• Anchor: if 80 of 100 dominant-allele carriers show the trait, penetrance = 80%.

E. Expressivity

Expressivity measures how strongly the phenotype is expressed among those who do show it.

• Definition: the degree or intensity of phenotypic expression in penetrant individuals.
• Variable expressivity: neurofibromatosis type 1—carriers range from a few café-au-lait spots to numerous tumours.
• Contrast with penetrance: penetrance is whether the trait appears (all-or-none, across a group); expressivity is how much it appears (a spectrum, within an individual).

IV. Cytoplasmic Inheritance

Genes in organelle genomes are transmitted through the cytoplasm, giving inheritance patterns independent of nuclear chromosomes.

A. Definition

Cytoplasmic inheritance is the transmission of characters by DNA located in cytoplasmic organelles rather than the nucleus.

• Key features: non-Mendelian ratios; reciprocal crosses give different results; usually uniparental (maternal) because the egg supplies the cytoplasm.
• Also called: extranuclear or extrachromosomal inheritance.

B. Inheritance of Mitochondrial DNA

Mitochondrial genes pass almost exclusively from mother to all offspring.

• mtDNA: a small circular genome (~16.6 kb in humans, 37 genes) encoding rRNAs, tRNAs and respiratory-chain subunits.
• Maternal transmission: sperm mitochondria are excluded or degraded at fertilization, so both sons and daughters inherit only the mother's mtDNA, but only daughters pass it on.
• Example: Leber's hereditary optic neuropathy (LHON) shows maternal-line inheritance with no paternal transmission.

C. Inheritance of Chloroplast DNA

Plastid genes are transmitted through the maternal cytoplasm in most plants.

• cpDNA: circular genome (~120–160 kb) encoding photosynthesis and plastid-translation components.
• Segregation: during cell division plastids sort randomly into daughter cells, producing green, white or variegated sectors.

D. Examples

Classic cases confirm organellar and cytoplasmic control.

1. Drug resistance in Chloroplast: in Chlamydomonas, streptomycin resistance maps to cpDNA and is inherited from the mt⁺ parent only—demonstrating uniparental chloroplast inheritance.
2. Four O'clock plant (Mirabilis jalapa): Correns showed leaf colour (green, white, variegated) depends solely on the female parent's branch. Seeds from a green branch → green; from a white branch → white; from variegated → mixed, regardless of pollen source—because plastids come from the egg.
3. Kappa particles in Paramecium: "killer" strains carry cytoplasmic kappa particles (endosymbiotic bacteria, Caedibacter) producing paramecin, lethal to sensitive strains. Maintenance requires the dominant nuclear gene K; loss of kappa turns killers sensitive—a nuclear-cytoplasmic partnership.
4. Snail shell coiling (Limnaea peregra): coiling direction shows maternal effect—the offspring's phenotype is set by the mother's genotype, not its own.
   • Dextral (D) dominant over sinistral (d): an dd mother from a Dd cross produces dextral offspring because the mother's genotype patterned the egg cytoplasm and spindle orientation.
   • Distinction: this is a nuclear gene acting through the cytoplasm, differing from true organellar inheritance—the phenotype lags one generation behind the genotype.