Inheritance of Two Genes, Polygenic Inheritance & Pleiotropy - Biology

INHERITANCE OF TWO GENES

Introduction

• Mendel conducted dihybrid crosses - crosses between plants differing in two characters simultaneously
• Example: Seed color (yellow/green) AND seed shape (round/wrinkled)

Mendel's Dihybrid Cross Experiment

Parental Cross:

• P generation: Round Yellow seeds (RRYY) × Wrinkled Green seeds (rryy)
• R = Round (dominant), r = wrinkled (recessive)
• Y = Yellow (dominant), y = green (recessive)

F₁ Generation:

• All F₁ plants: Round, Yellow (RrYy)
• This showed:
  • Yellow is dominant over green
  • Round is dominant over wrinkled
• Results were identical to separate monohybrid crosses

F₂ Generation (when F₁ selfed):

• Four phenotypic classes appeared:
  1. Round, Yellow
  2. Round, Green
  3. Wrinkled, Yellow
  4. Wrinkled, Green
• Phenotypic ratio: 9:3:3:1
  • 9 Round, Yellow
  • 3 Wrinkled, Yellow
  • 3 Round, Green
  • 1 Wrinkled, Green

Key Observations:

1. Seed shape inheritance (Round/Wrinkled) was independent of seed color (Yellow/Green)
2. Each trait segregated in 3:1 ratio (like monohybrid cross)
3. The 9:3:3:1 ratio can be derived as: (3 Round : 1 Wrinkled) × (3 Yellow : 1 Green)

Gamete Formation in F₁

From RrYy genotype:

• Segregation of R/r is independent of segregation of Y/y
• Four types of gametesproduced in equal proportion:
  1. RY (25%)
  2. Ry (25%)
  3. rY (25%)
  4. ry (25%)

Using Punnett Square :

• Female gametes (♀): RY, Ry, rY, ry
• Male gametes (♂): RY, Ry, rY, ry
• Total: 16 boxes in Punnett square

F₂ Genotypic Combinations:

• Multiple genotypes possible
• But only 4 phenotypes (due to dominance)
• Phenotypic ratio: 9:3:3:1
• Genotypic ratio: More complex (1:2:1:2:4:2:1:2:1)

LAW OF INDEPENDENT ASSORTMENT

Statement

"When two pairs of traits are combined in a hybrid, segregation of one pair of characters is independent of the other pair of characters."

Explanation Using Punnett Square

For F₁ RrYy plant:

1. R and r segregation:
   • 50% gametes have R
   • 50% gametes have r
2. Y and y segregation:
   • 50% gametes have Y
   • 50% gametes have y
3. Independence means:
   • Of the 50% R-bearing gametes:
     • 50% also have Y → 25% RY
     • 50% have y → 25% Ry
   • Of the 50% r-bearing gametes:
     • 50% also have Y → 25% rY
     • 50% have y → 25% ry

Result: Four gamete types (RY, Ry, rY, ry) each at 25% frequency

Derivation of 9:3:3:1 Ratio

The ratio can be mathematically derived:

(3 Round : 1 Wrinkled) × (3 Yellow : 1 Green) 

= 9 Round,Yellow : 3 Wrinkled,Yellow : 3 Round,Green : 1 Wrinkled,Green

Key Points

• This law applies when genes are on different chromosomes or far apart on same chromosome
• Mendel observed this ratio for several pairs of characters
• The law explains genetic variation in sexually reproducing organisms

CHROMOSOMAL THEORY OF INHERITANCE

Historical Background

Mendel's Work (1865):

• Remained unrecognized until 1900
• Reasons for delay:
  1. Communication was not easy
  2. Concept of discrete, non-blending factors was not accepted
  3. Mathematical approach to biology was new and unacceptable
  4. No physical proof of "factors" existence

Rediscovery (1900):

• Three scientists independently rediscovered: de Vries, Correns, von Tschermak
• By this time: Advancements in microscopy
• Discovery of chromosomes (colored bodies in nucleus)
• Chromosomes observed to double and divide before each cell division

By 1902:

• Chromosome movement during meiosis worked out
• Walter Sutton and Theodore Boveri noted parallel behavior

The Theory

Key Observation:Behavior of chromosomes is parallel to behavior of genes

Correlation Established:

• Chromosomes and genes both occur in pairs
• Two alleles of a gene pair are located on homologous sites on homologous chromosomes
• Used chromosome movement during meiosis to explain Mendel's laws

Comparison between Chromosomes and Genes

Called: Chromosomal Theory of Inheritance

Meiosis and Independent Assortment 

During Meiosis I - Anaphase:

• Homologous chromosome pairs can align at metaphase plate independently
• Different combinations of maternal and paternal chromosomes possible

Independent Assortment:Shows two possibilities with 4 chromosomes (2 pairs):

Possibility I:

• Orange and green chromosomes segregate together
• Yellow and red chromosomes segregate together

Possibility II:

• Orange and red chromosomes segregate together
• Yellow and green chromosomes segregate together

This explains: Why different gene pairs segregate independently (if on different chromosomes)

LINKAGE AND RECOMBINATION

Discovery - Thomas Hunt Morgan

Model Organism: Drosophila melanogaster (Fruit Fly)

Advantages:

1. Grown on simple synthetic medium in laboratory
2. Complete life cycle in about two weeks
3. Single mating produces large number of progeny
4. Clear differentiation of sexes (male and female easily distinguishable)
5. Many hereditary variations visible with low power microscopes

Morgan's Dihybrid Crosses

Observation:

• Morgan studied sex-linked genes in Drosophila
• Conducted dihybrid crosses similar to Mendel's pea crosses

Key Finding:

• Two genes did NOT segregate independently
• F₂ ratio deviated significantly from 9:3:3:1 ratio

Reason:

• The two genes were located on the same chromosome (X chromosome)
• When genes are on same chromosome: proportion of parental gene combinations >> non-parental type

Linkage

Definition:

• Linkage: Physical association of genes on a chromosome
• Linked genes tend to be inherited together

Morgan's Term:

• Recombination: Generation of non-parental gene combinations

Strength of Linkage

Morgan's observations:

1. Tightly linked genes:
   • Example: white and yellow genes
   • Showed only 1.3% recombination
   • Very low frequency of non-parental combinations
2. Loosely linked genes:
   • Example: white and miniature wing
   • Showed 37.2% recombination
   • Higher frequency of non-parental combinations

Conclusion:

• Distance between genes determines linkage strength
• Greater distance → Higher recombination → Weaker linkage

Linkage in Drosophila

Cross A: y (yellow body) and w (white eye)

Parental:

• Female: y w / y w (Yellow body, White eye)
• Male: y⁺ w⁺ / Y (Wild type - normal body, normal eye)

F₁ generation:

• Female: y⁺ w⁺ / y w (Wild type appearance)
• Male: y w / Y (Yellow body, White eye)

Gametes from F₁ female:

• Parental type: 98.7%
  • y⁺ w⁺ (Wild type)
  • y w (Yellow, white)
• Recombinant type: 1.3%
  • y⁺ w (White eye only)
  • y w⁺ (Yellow body only)

F₂ generation:Shows mostly parental combinations with very few recombinants

Cross B: w (white eye) and m (miniature wing)

Parental:

• Female: w m / w m (White eye, Miniature wing)
• Male: w⁺ m⁺ / Y (Wild type)

F₁ generation:

• Female: w⁺ m⁺ / w m (Wild type)
• Male: w m / Y (White, miniature)

Gametes from F₁ female:

• Parental type: 62.8%
  • w⁺ m⁺ (Wild type)
  • w m (White, miniature)
• Recombinant type: 37.2%
  • w⁺ m (Miniature wing only)
  • w m⁺ (White eye only)

F₂ generation:Shows significant proportion of both parental and recombinant types

Genetic Mapping

Alfred Sturtevant (Morgan's student):

• Used frequency of recombination between gene pairs as a measure of distance between genes
• 'Mapped' position of genes on chromosome
• Created genetic maps

Significance:

• Genetic maps extensively used in genome sequencing projects
• Example: Human Genome Sequencing Project used genetic maps as starting point

Note:

• Dominant wild-type alleles represented with (+) sign in superscript
• Example: y⁺ = normal body color, w⁺ = normal eye color

Key Inference:

• Strength of linkage between y and w is higher than w and m
• This is why y-w shows only 1.3% recombination while w-m shows 37.2%

POLYGENIC INHERITANCE

Definition

Polygenic Inheritance:

• Also called quantitative or multiple-gene inheritance
• A single trait is controlled by two or more independent genes
• Effects of genes are additive (add together)

Alternative name: Multiple-factor inheritance

Characteristics of Polygenic Inheritance

1. Polygene:
   • A gene that contributes a small amount to phenotype
   • Effect of single gene often too small to be detected
2. Cumulative/Additive Effects:
   • Multiple genes produce additive effects on the trait
3. Different from Multiple Allelism:
   • Multiple alleles: Different versions of single gene at ONE locus
   • Polygenic traits: Alleles at MANY loci
4. Epistasis:
   • May or may not be involved
   • Often described as contributing (active) vs non-contributing (null) alleles
5. Continuous Variation:
   • Polygenic traits show continuous variation in population
   • Bell-shaped distribution in large populations
6. Prediction:
   • Complex to predict phenotype
   • Statistical analysis used to estimate population parameters
7. Environmental Influence:
   • Traits controlled by many genes usually show continuous variation
   • Examples: height, skin color

Polygenic Inheritance in Humans

Common polygenic traits:

• Skin color
• Hair color
• Height
• Eye color
• Blood pressure
• Intelligence
• Susceptibility to some diseases
• Longevity

Important Note:

• Both genes AND environment influence these traits

Example: Skin Pigmentation

From Light to Dark

Model (simplified):

• Controlled by many loci
• Consider three unlinked loci: A/a, B/b, C/c

Allele notation:

• Capital letters (A, B, C): Alleles contributing to darker pigmentation
• Small letters (a, b, c): Contribute less to pigmentation

Cross:

• Parents: AABBCC (dark) × aabbcc (light)
• F₁: AaBbCc (intermediate color)

F₂ (when F₁ × F₁):

• Distribution of phenotypes from very dark to very light
• Approximate ratio: 1 : 6 : 15 : 20 : 15 : 6 : 1
  • From very dark to very light
  • Represents combinations with differing numbers of contributing alleles

Explanation:

• More contributing alleles (A, B, C) → Darker skin
• Fewer contributing alleles → Lighter skin
• Intermediate combinations → Intermediate shades

Example: Height

Characteristics:

• Influenced by many genes (hundreds)
• Also influenced by environment:
  • Nutrition
  • Health

Result:

• Combined effect of many loci + environmental input
• Produces continuous variation

Example: Eye Color

Characteristics:

• Polygenic trait
• Small number of major genes + several modifier genes
• Determine wide range of human eye colors
• Expression is complex
• Influenced by multiple loci

PLEIOTROPY

Definition

Pleiotropy:

• Phenomenon where a single gene influences two or more seemingly unrelated phenotypic traits
• Term from Greek meaning "many ways"

Pleiotropy

Pleiotropic Gene:

• A gene that exhibits multiple phenotypic expression

Example : Phenylketonuria (PKU)

In Humans:

Cause:

• Mutation in gene for enzyme phenylalanine hydroxylase
• Single gene mutation

Multiple Effects (if untreated):

1. Metabolic disorder:
   • Affects metabolism of phenylalanine (amino acid)
2. Intellectual disability:
   • Mental retardation
3. Pigmentation changes:
   • Light skin
   • Light hair
   • Due to reduced melanin synthesis
4. Other systemic effects