Principles of Inheritance and Variation — Long Notes

Genetics is the branch of biology that studies inheritance (how traits pass from parents to offspring) and variation (differences among individuals). Its modern foundation was laid by an Austrian monk, Gregor Johann Mendel, using the garden pea Pisum sativum between 1856 and 1863.

1. Mendel's Approach

Why pea? — pea is annual, bisexual, self-pollinating (so lines can be kept "true-breeding"), easy to cross-pollinate by hand, and shows clear contrasting characters.

Mendel picked 7 contrasting characters:

Character	Dominant	Recessive
Stem length	Tall	Dwarf
Flower colour	Violet	White
Flower position	Axial	Terminal
Pod shape	Inflated	Constricted
Pod colour	Green	Yellow
Seed shape	Round	Wrinkled
Seed colour	Yellow	Green

He kept meticulous quantitative records of large numbers of offspring — the statistical rigour was his innovation.

2. Basic Terminology

• Gene — a segment of DNA that codes for a trait.
• Allele — alternative forms of a gene (e.g. tall allele T, dwarf allele t).
• Homozygous (TT or tt) — both alleles the same. Heterozygous (Tt) — different alleles.
• Genotype — genetic constitution; Phenotype — observable trait.
• Dominant — expressed in the heterozygote (T over t → tall). Recessive — masked in the heterozygote.
• True-breeding line — self-pollinated for generations without variation.

3. Mendel's Laws

3.1 Law of Dominance

In a cross of true-breeding tall × dwarf, all F₁ are Tall (Tt) — only the dominant allele shows. Explains 3:1 F₂ ratio.

3.2 Law of Segregation ("purity of gametes")

The two alleles of a gene separate during gamete formation; a gamete receives only one allele. In F₁ (Tt), gametes are 50% T and 50% t. The 3:1 F₂ ratio arises from random fusion.

3.3 Law of Independent Assortment

Alleles of different genes sort independently during gamete formation. Demonstrated by dihybrid crosses (e.g. round yellow × wrinkled green pea seeds).

4. Monohybrid and Dihybrid Crosses

4.1 Monohybrid (one trait, e.g. plant height)

• Parents: TT (Tall) × tt (Dwarf).
• F₁: all Tt (Tall).
• F₁ × F₁ → F₂: 1 TT : 2 Tt : 1 tt genotypes; 3 Tall : 1 Dwarf phenotypes.

Test cross — F₁ × homozygous recessive (Tt × tt). Reveals whether an F₁ plant is Tt or TT:

• If Tt: half tall + half dwarf.
• If TT: all tall.

4.2 Dihybrid (two traits)

• Parents: Round Yellow (RRYY) × wrinkled green (rryy).
• F₁: all RrYy (Round Yellow).
• F₁ × F₁ → F₂: 16 combinations → 9 Round Yellow : 3 Round Green : 3 Wrinkled Yellow : 1 Wrinkled Green.

This 9:3:3:1 ratio proves independent assortment (each single-trait ratio is still 3:1).

5. Deviations from Mendel's Rules

Mendel's simple dominance model is a first approximation. Later work uncovered many refinements:

5.1 Incomplete Dominance

• Heterozygote shows an intermediate phenotype.
• Example: Antirrhinum (snapdragon) — RR (Red) × rr (White) → Rr (Pink).
• F₂ ratio: 1 Red : 2 Pink : 1 White — phenotype ratio matches genotype ratio.

5.2 Co-dominance

• Both alleles are expressed together in the heterozygote.
• Classic example: the human ABO blood group system, governed by a single gene with three alleles I^A, I^B, i.
• I^A and I^B are both dominant over i but co-dominant with each other.
• Genotypes and phenotypes:

Genotype	Antigens on RBC	Phenotype
I^AI^A, I^Ai	A	A
I^BI^B, I^Bi	B	B
I^AI^B	A and B	AB
ii	none	O

5.3 Multiple Alleles

• More than two alleles exist for a gene in a population (though any individual carries only 2).
• ABO with 3 alleles; other examples in fur colour in rabbits, coat colour in mice.

5.4 Pleiotropy

• A single gene affects multiple, seemingly unrelated traits.
• Example: Phenylketonuria (PKU) — a mutation in phenylalanine hydroxylase → phenylalanine accumulates → causes mental retardation, hair depigmentation, and skin issues.
• Sickle-cell anaemia also shows pleiotropy (haemolysis, splenomegaly, joint pain, low resistance to malaria).

5.5 Polygenic Inheritance

• Multiple genes control one trait; effects add up.
• Traits show continuous variation (a range, not distinct classes) — height, skin colour, intelligence.
• Environmental factors also modulate the expression.

6. Chromosomal Theory of Inheritance

Proposed independently by Sutton and Boveri (1902). Key insight: chromosomes behave in meiosis exactly as Mendel's factors do — they come in pairs, separate during gamete formation, and re-unite at fertilisation.

T. H. Morgan verified it experimentally with the fruit fly Drosophila melanogaster, showing:

• Genes are located on chromosomes.
• Genes on the same chromosome tend to be linked (inherited together).
• Linkage can be broken by crossing over during meiosis → recombination.

7. Linkage and Recombination

• Linkage — physical association of genes on the same chromosome; violates independent assortment.
• Recombination — new gene combinations arise from crossing over.
• Recombination frequency between two genes ∝ distance between them (basis of genetic mapping).

8. Sex Determination

Genetic sex is decided by chromosomes:

Organism	Mechanism	Male	Female
Humans, Drosophila	XY	XY	XX
Grasshopper, cockroach	XO	XO	XX
Birds, moths, butterflies	ZW	ZZ	ZW
Honey bees	Haplo-diploidy	Haploid (unfertilised)	Diploid

Human males are heterogametic (produce X and Y sperms); the father's sperm decides the sex of the child.

9. Mutations

Mutation = a heritable change in the DNA (and hence phenotype).

Two broad classes:

• Chromosomal mutations — large-scale changes: deletion, duplication, inversion, translocation, or number changes (aneuploidy, polyploidy).
• Gene (point) mutations — a single base substitution. Example: sickle-cell anaemia — GAG → GUG in the β-globin mRNA → Glutamate → Valine at position 6 → sticky HbS, RBCs sickle under low O₂.
• Frame-shift mutations — insertion/deletion of one or two bases shifts the reading frame → downstream sequence garbled.

Mutations may be caused by:

• Mutagens — X-rays, gamma rays, UV, chemical carcinogens (e.g. mustard gas).
• Spontaneous errors during replication.

10. Genetic Disorders

10.1 Mendelian Disorders (single-gene)

Disorder	Inheritance	Description
Haemophilia	X-linked recessive	Missing clotting factor (VIII or IX); minor injury → uncontrolled bleeding.
Colour blindness	X-linked recessive	Red-green defect; ~8% men, ~0.4% women.
Sickle-cell anaemia	Autosomal recessive	HbS RBCs sickle; heterozygotes protected from malaria.
Phenylketonuria (PKU)	Autosomal recessive	Missing phenylalanine hydroxylase → mental retardation.
Thalassaemia	Autosomal recessive	Defective globin synthesis → severe anaemia.
Cystic fibrosis	Autosomal recessive	Thick mucus in lungs & pancreas.

Pedigree analysis can trace patterns across families.

10.2 Chromosomal Disorders (number)

Disorder	Chromosome change	Karyotype	Features
Down's syndrome	Trisomy 21	47, +21	Short, palm crease, mental retardation, congenital heart defects
Klinefelter's syndrome	Extra X	47, XXY	Male with breast development (gynaecomastia), sterile
Turner's syndrome	Missing X	45, XO	Female, short stature, sterile

Key take-aways

1. Mendel's genius: quantitative analysis of large offspring counts revealed particulate inheritance long before DNA was known.
2. Three laws — dominance, segregation, independent assortment.
3. Later refinements (incomplete dominance, co-dominance, polygenic, pleiotropy) enrich rather than overturn Mendel's model.
4. Chromosomes (Sutton–Boveri) and Morgan's work with Drosophila explained the physical basis of Mendel's factors, including linkage and recombination.
5. Sex determination varies across species; mutations underlie evolution and disease; genetic disorders may be Mendelian (single-gene) or chromosomal (whole chromosome changes).