Unit 1: Mendelian inheritance

I. Foundations of Mendelian Inheritance

Mendelian inheritance originates in Gregor Mendel’s experiments on garden pea (Pisum sativum), reported in 1865 and published in 1866. Mendel showed that hereditary determinants—now called genes—are transmitted as discrete units rather than permanently blending in offspring.

A. Governing framework

The analysis of inheritance depends on genes, alleles, chromosomes, and the relationship between genotype and phenotype.

• Gene: A hereditary unit occupying a defined chromosomal position, or locus, and contributing to a functional product or trait.
• Alleles: Alternative forms of a gene; for example, T and t may specify tall and dwarf pea plants.
• Genotype: The allelic constitution of an organism, such as TT, Tt, or tt.
• Phenotype: The observable characteristic produced by genotype interacting with environment, such as plant height.
• Homozygous condition: Both alleles at a locus are identical—TT or tt.
• Heterozygous condition: The two alleles differ—Tt.
• Diploid convention: A diploid organism normally carries two alleles per autosomal locus, one inherited from each parent.
• Gametic convention: Meiosis produces haploid gametes containing one allele from each locus.
• Cross notation: P, F₁, and F₂ denote parental, first-filial, and second-filial generations, respectively.

II. Historical Concepts of Heredity

Ideas about heredity changed from speculative explanations to experimentally testable models of genes, chromosomes, and DNA.

A. Pre- and post-Mendelian concepts of heredity

Pre-Mendelian theories lacked a particulate mechanism, whereas post-Mendelian discoveries connected Mendel’s factors to chromosomes and extended inheritance beyond simple dominance.

1. Pre-Mendelian concepts:

   • Preformationism: Seventeenth- and eighteenth-century thinkers proposed that a miniature organism already existed in the egg or sperm; development merely enlarged it.
   • Epigenesis: Associated with ideas traceable to Aristotle, this view held that structures arise progressively during development rather than existing fully formed.
   • Blending inheritance: Parental characteristics were thought to mix irreversibly, like two fluids. This could not explain the reappearance of a recessive trait in Mendel’s F₂.
   • Inheritance of acquired characters: Jean-Baptiste Lamarck proposed in 1809 that traits acquired through use or disuse could be inherited; ordinary genetic inheritance does not support this general mechanism.
   • Pangenesis: Charles Darwin proposed in 1868 that body parts released hereditary “gemmules” that accumulated in reproductive organs.

2. Post-Mendelian concepts:

   • Chromosome theory: Walter Sutton and Theodor Boveri, around 1902–1903, independently related Mendelian factors to chromosome behavior during meiosis.
   • Linkage and recombination: Thomas Hunt Morgan’s Drosophila work showed that genes on one chromosome form linkage groups but may recombine through crossing over.
   • Extended allelic relationships: Incomplete dominance, codominance, multiple alleles, lethal alleles, and sex linkage showed that dominance is not universal.
   • Gene interaction: Epistasis demonstrated that alleles at one locus can modify or mask expression at another locus.
   • Molecular interpretation: DNA was established as genetic material, and genes came to be understood as DNA sequences whose products influence cellular functions.
   • Non-Mendelian transmission: Mitochondrial inheritance, chloroplast inheritance, genomic imprinting, and maternal effects produce patterns not explained by simple nuclear segregation alone.

III. Mendel’s Laws

Mendelian laws describe allele transmission when loci segregate normally, gametes unite randomly, and complications such as linkage, meiotic drive, or strong viability differences are absent.

A. Mendelian principles of heredity

Mendel’s principles explain how discrete alleles persist and are redistributed across generations.

• Principle of unit factors: Traits are governed by discrete hereditary factors occurring in pairs in diploid organisms; modern genetics identifies these factors as alleles.
• Principle of dominance: In Mendel’s pea characters, one allele determined the heterozygous phenotype. Thus Tt was tall when T was dominant to t.
• Law of segregation: The two alleles of a locus separate during gamete formation, so each gamete receives one allele.

Tt × Tt → 1 TT : 2 Tt : 1 tt
Phenotypes → 3 tall : 1 dwarf

• T = dominant tall allele.
• t = recessive dwarf allele.
• The 1:2:1 ratio is genotypic; 3:1 is phenotypic under complete dominance.

• Law of independent assortment: Alleles of different genes assort independently into gametes when the genes are on different chromosomes, or sufficiently far apart on the same chromosome.

RrYy → RY, Ry, rY, ry in equal expected proportions
F₂ phenotype ratio = 9 : 3 : 3 : 1

• R/r = seed-shape alleles; Y/y = seed-colour alleles.
• The ratio assumes complete dominance, independent assortment, and equal survival.

• Test cross: Crossing an individual with a dominant phenotype to a homozygous recessive tester reveals the unknown genotype; Tt × tt gives an expected 1 tall : 1 dwarf.
• Probability basis: The product rule combines independent events; the chance of rryy from RrYy × RrYy is (1/4)(1/4) = 1/16.
• Limitations: Linkage alters dihybrid ratios, while incomplete dominance, epistasis, penetrance, and environmental effects alter expected phenotype categories without invalidating segregation itself.

IV. Categories of Traits

Traits can be classified by whether phenotypes form discrete classes or display measurable gradation.

A. Qualitative and quantitative traits

Qualitative traits usually reflect a few genes with conspicuous effects, whereas quantitative traits commonly reflect many genes plus environmental variation.

1. Qualitative traits:

   • Phenotypic pattern: Individuals occupy distinct categories, such as purple versus white pea flowers.
   • Genetic control: One or a few loci often have major effects, allowing ratios such as 3:1, 1:2:1, or 9:3:3:1.
   • Measurement: Classification is categorical rather than numerical.
   • Environmental sensitivity: Environmental influence may occur, but it usually does not erase the basic classes.

2. Quantitative traits:

   • Phenotypic pattern: Values vary by degree, as in height, body mass, crop yield, or milk production.
   • Genetic control: Numerous loci often contribute small effects, with environmental factors adding variation.
   • Measurement: Traits use numerical units such as centimetres, grams, or kilograms per hectare.
   • Distribution: Large populations frequently approach a bell-shaped distribution because many genetic and environmental effects combine.
   • Heritability: The phenotypic variance may be partitioned conceptually as:

Vₚ = Vɢ + Vₑ + Vɢ×ₑ

• Vₚ = phenotypic variance.
• Vɢ = genetic variance.
• Vₑ = environmental variance.
• Vɢ×ₑ = genotype-by-environment interaction variance.

V. Polygenic Inheritance

Polygenic inheritance occurs when several genes jointly influence one character, usually through small cumulative contributions.

A. Polygenes and continuous variations

Polygenes produce continuous variation because many genotypic combinations generate closely spaced phenotypic values that are further modified by environment.

• Polygenes: Multiple, usually non-allelic genes affecting the same quantitative character; each contributing allele may add a small phenotypic increment.
• Additive model: With equal additive effects, phenotype can be represented as:

P = μ + Σaᵢ + E

• P = observed phenotypic value.
• μ = population mean.
• aᵢ = additive effect of the contributing allele at locus i.
• E = environmental deviation.

• Continuous variation: Human height and wheat yield show many intermediate values rather than sharply separated Mendelian classes.
• Number of classes: In an ideal additive model involving n independently assorting gene pairs, the F₂ may contain up to 2n + 1 phenotypic classes.
• Extreme-frequency principle: If n equal-effect loci distinguish two pure parental lines, the expected frequency of either parental extreme in F₂ is (1/4)ⁿ.
• Environmental contribution: Nutrition, temperature, water supply, disease, and developmental conditions broaden or merge genetically determined classes.
• Mendelian basis: Each contributing locus still segregates according to Mendel’s laws; continuity emerges from the combined effects of many loci.

VI. Multifactorial Explanation of Quantitative Traits

The multiple-factor framework reconciles continuous phenotypic variation with particulate Mendelian inheritance.

A. Multiple factor hypothesis

The multiple factor hypothesis states that a quantitative trait is controlled by several Mendelian factors whose cumulative effects create a graded series of phenotypes.

• Historical evidence: Herman Nilsson-Ehle’s studies of wheat kernel colour, published in 1909, showed that several independently segregating genes could produce multiple shades from white to dark red.
• Cumulative alleles: Each contributing dominant allele increased pigment intensity, so plants with more contributing alleles had darker kernels.
• Two-locus example: For A₁a₁ A₂a₂ × A₁a₁ A₂a₂, an additive model can produce five classes containing zero, one, two, three, or four contributing alleles.
• Expected distribution: Under equal effects and no environmental overlap, the five F₂ classes follow:

1 : 4 : 6 : 4 : 1

• Distinction from simple dominance: A contributing allele adds an increment rather than merely masking its alternative allele.
• Modern extension: Quantitative-trait loci may have unequal effects and may show dominance, epistasis, linkage, pleiotropy, and genotype–environment interaction.
• Significance: The hypothesis explains how discrete genes can underlie continuous traits and provides a foundation for plant breeding, animal improvement, and quantitative genetics.

VII. Experimental Model Organisms

Model organisms are selected because their biological and experimental properties make general genetic principles easier to discover and test.

A. Study of model organisms: Drosophila, Arabidopsis, garden pea, E. coli, and mice

These organisms provide complementary systems ranging from bacterial gene regulation to inheritance and development in multicellular eukaryotes.

• Drosophila—Drosophila melanogaster:

  • Advantages: A generation takes roughly ten days under favourable laboratory conditions; flies produce many offspring and have only four chromosome pairs.
  • Genetic contribution: Morgan’s white-eye experiments established sex-linked inheritance, while recombination frequencies enabled chromosome mapping.
  • Special feature: Large polytene chromosomes in larval salivary glands permit visible cytogenetic analysis.

• Arabidopsis—Arabidopsis thaliana:

  • Advantages: This small flowering plant has a short life cycle, prolific seed production, five chromosome pairs, and a compact genome.
  • Genetic contribution: Self-fertilization preserves lines, while controlled crosses support studies of flowering, development, signalling, and plant–pathogen interactions.
  • Experimental value: Transformation using Agrobacterium tumefaciens facilitates gene-function analysis.

• Garden pea—Pisum sativum:

  • Advantages: Peas possess clear contrasting characters, naturally self-pollinate, and can be cross-pollinated manually.
  • Genetic contribution: Mendel used traits such as seed shape, seed colour, flower colour, and stem length to formulate segregation and independent assortment.
  • Limitation: Its longer generation time and larger genome make it less convenient than Arabidopsis for modern molecular work.

• E. coli—Escherichia coli:

  • Advantages: This haploid bacterium grows rapidly, forms large populations, and can be cultured on defined media.
  • Genetic contribution: Conjugation, transformation, and transduction revealed mechanisms of bacterial gene transfer; the lac operon became a central model of gene regulation.
  • Experimental value: Plasmids and selectable markers make E. coli fundamental to cloning and recombinant-DNA technology.

• Mice—Mus musculus:

  • Advantages: Mice are mammals with organ systems and many genes homologous to those of humans.
  • Genetic contribution: Inbred strains, pedigrees, transgenic animals, knockouts, and CRISPR-edited lines permit controlled study of gene function.
  • Biomedical value: Mouse models investigate development, immunity, cancer, metabolism, behaviour, and inherited disease.
  • Limitation: Greater cost, longer generation time, smaller family size, and ethical requirements distinguish mice from microbial or invertebrate models.