PB Ch 12. Exceptions to Laws of Inheritance

While Mendel's Laws are foundational, they are not universally applicable. Many biological phenomena represent exceptions or modifications to his original principles.

Criticisms of Mendel's Laws

Limited Universality of Independent Assortment

• The Law of Independent Assortment applies only to genes located on different (non-homologous) chromosomes.
• Cytological studies revealed that genes located on the same chromosome are physically linked and tend to be inherited together.
• This phenomenon, called linkage, completely violates independent assortment.
• Bateson and Punnett's experiments on sweet pea were among the first to demonstrate linkage, and Thomas Hunt Morgan's work in Drosophila formalized the chromosomal theory of linkage.
• Critical point: Of Mendel's seven pea characters, some genes are located on the same chromosomes — yet they behaved as if independently assorting because they were far apart on the chromosome (allowing frequent recombination). Had Mendel chosen genes that were closely linked, he would not have observed 9:3:3:1 ratios.

Blending vs. Particulate Inheritance

• Many 19th century biologists dismissed Mendel's theory because traits often appeared to blend in offspring (e.g., intermediate heights).
• This blending was assumed to mean hereditary material mixed.
• We now understand that:
  • (a) some traits are controlled by many genes (polygenic inheritance), producing a continuous range of phenotypes, and
  • (b) incomplete dominance creates intermediate phenotypes without actual blending of alleles.
  • The alleles themselves remain distinct and particulate.

Equal Viability Assumption

• Mendel's 3:1 ratio assumes all genotypes survive equally well.
• In reality, some genotypes are lethal.
• For example, in mice, the allele for yellow coat colour is lethal in homozygous condition — yellow homozygotes are never born, giving a 2:1 ratio instead of 3:1.
• Such lethal alleles alter expected Mendelian ratios.

Gene Interaction Not Considered

• Mendel's model assumed one gene affects one character independently.
• In reality, many characters are affected by interactions between multiple genes (epistasis), producing modified F2 ratios such as 9:7, 12:3:1, 15:1, and others.
• These are not exceptions to the mechanism of segregation — they are extensions that reflect biochemical cooperation or interference between gene products.

Sex-Linked Inheritance

• Mendel worked only with autosomally inherited characters.
• Genes located on the sex chromosomes (X or Y) follow different patterns, including criss-cross inheritance and different phenotypic ratios in males and females.
• For example, colour blindness and haemophilia in humans are X-linked and do not follow typical Mendelian autosomal ratios.

Cytoplasmic (Maternal) Inheritance

• Mendel's laws apply only to nuclear (chromosomal) genes.
• Some traits are inherited through the cytoplasm — particularly via mitochondrial and chloroplast DNA — and show maternal inheritance patterns that completely violate Mendelian expectations.
• The offspring of reciprocal crosses behave differently, which is the hallmark of cytoplasmic inheritance.

Exceptions to Mendelian Ratios

Incomplete Dominance

• Definition: When a dominant allele does not completely mask the recessive allele, the heterozygote (F1) shows an intermediate phenotype between the two homozygotes. The alleles remain distinct but neither fully dominates the other
• Classic example: In four-o'clock plant (Mirabilis jalapa) and snapdragon (Antirrhinum majus), a cross between red (RR) and white (rr) flowered plants produces pink (Rr) F1. This gives a 1:2:1 ratio in F2 (1 red : 2 pink : 1 white) instead of Mendel's 3:1.

Incomplete Dominance — Mirabilis jalapa (Rr × Rr)

F2 Ratio: 1 Red (RR) : 2 Pink (Rr) : 1 White (rr) — Phenotypic ratio = Genotypic ratio

Codominance

• Definition: Both alleles in a heterozygote are fully and simultaneously expressed — neither is dominant or recessive. The F1 phenotype is not intermediate; it displays both parental phenotypes side by side.
• Example 1: ABO blood groups in humans — individuals with genotype IᴮIᴮ express both A and B antigens simultaneously, giving blood group AB.
• Example 2: In cattle, crossing white-coated (WW) with red-coated (ww) produces F1 offspring with a roan coat — a mixture of red and white hairs (not a blend of red and white into pink). Each type of hair is independently coloured.
• Key distinction: Incomplete dominance produces a blended intermediate phenotype. Codominance produces both original phenotypes simultaneously in the same individual.

Lethal Genes

• Definition: A gene that causes the death of its carrier when present in a critical genotype (usually homozygous) is called a lethal gene. Lethal genes modify the expected Mendelian ratios.
• Classic example (Recessive lethal — Mice): The allele Aʸ for yellow coat colour in mice is dominant over the wild-type agouti allele (a) for coat colour, but when homozygous (AʸAʸ) it causes early embryonic death. Therefore, yellow mice are always heterozygous (Aʸa). A cross of yellow × yellow gives:

Result: 2 Yellow : 1 Agouti (instead of the expected 3:1). The modification is entirely due to lethality of the homozygous dominant.

• Classic example (Dominant lethal — Humans): Huntington's disease is caused by a dominant lethal allele. Affected individuals (heterozygous) develop a progressive neurological disorder that typically manifests in middle age (approximately ages 35–55). This delayed expression allowed Mendel-violating dominant lethals to persist in populations. I am not certain about the exact age range and recommend verifying from a clinical genetics source.

Pleiotropy

• Definition: A single gene affecting or controlling more than one phenotypic character is called a pleiotropic gene. The phenomenon is known as pleiotropism or pleiotropy.

Examples: 

• In Drosophila, the recessive gene for vestigial wings also affects the haltere (balancer), certain bristles, reproductive organ structure, egg production, and longevity.
• In humans, the recessive gene for phenylketonuria (PKU) produces multiple abnormal phenotypic traits: elevated phenylalanine in urine and blood, intellectual disability, reduced height, pigmentation changes, and widely spaced incisors.
• In wheat, a gene governing awns (Ona variety) also increases yield and seed weight.
• In cotton, the Punjab hairy lintless gene (lic) produces seeds without lint, incomplete leaf lancination, reduced boll size, and reduced fertility.
• Pleiotropy arises because a single gene product (enzyme or protein) participates in multiple biochemical pathways affecting different tissues or developmental processes.

Penetrance and Expressivity

• Penetrance refers to the frequency (proportion) of individuals carrying a gene in the appropriate genotype who actually show its phenotypic effect. It is expressed as a percentage.
• Complete penetrance: 100% of individuals with the genotype express the trait. Example: TT plants are always tall; tt plants are always dwarf in Mendel's pea experiments.
• Incomplete penetrance: Not all individuals carrying the gene express its effect. Example: The recessive gene for partial chlorophyll deficiency in lima bean expresses itself in only about 10% of individuals carrying it in homozygous condition. (I am not fully certain of this specific percentage; please verify from the original source.)

Expressivity refers to the degree or intensity of phenotypic expression of a gene in different individuals. It may be:

• Uniform expressivity: All individuals that express the gene do so to the same degree. Example: Wrinkled seed coat in pea — all homozygous recessive seeds are equally wrinkled.
• Variable expressivity: Different individuals expressing the gene do so to different degrees. Example: The gene for polydactyly in humans shows variable expressivity — some affected individuals have extra fingers on both hands, others only on one hand.

Phenocopy

• Phenocopy is the alteration of phenotype by environmental or nutritional factors to mimic a phenotype normally produced by a specific gene.
• For example, rickets caused by vitamin D deficiency is a phenocopy of vitamin D-resistant rickets (a genuine genetic condition).
• The individual is not genetically different; the environment mimics the genetically-caused phenotype. Phenocopies do not breed true.