Lecture 4

Mendelian Genetics and Its Modifications

Gregor Mendel and the Foundations of Genetics

Gregor Mendel's experiments with pea plants established the basic principles of heredity. He studied seven traits, each controlled by a single gene with two alleles, and observed clear patterns of inheritance.

• Mendel's First Law (Law of Segregation): Each organism carries two 'factors' (now called genes), one from each parent. These segregate randomly during gamete formation.

• Mendel's Second Law (Law of Independent Assortment): Genes for different traits assort independently during gamete formation.

• Dominant and Recessive Alleles: One allele may mask the expression of another (dominant vs. recessive).

• Phenotypic Ratios: F2 generation shows a 3:1 ratio for single traits and a 9:3:3:1 ratio for two traits.

From Mendel's Factors to Genes on Chromosomes

Mendel's 'factors' were later named genes, and their physical location was determined to be on chromosomes. The Boveri-Sutton chromosome theory explained how chromosome behavior during meiosis accounts for Mendel's laws.

• Chromosome Theory of Inheritance: Genes are located on chromosomes, and their segregation and independent assortment are explained by meiosis.

Chromosomes and Cell Division

Chromosome Structure and Terminology

Chromosomes are composed of DNA and proteins. Key terms include:

• Chromatid: Each chromosome consists of one or two chromatids depending on the cell cycle stage.

• Homologous Chromosomes: Maternal and paternal versions of a chromosome, carrying different alleles.

• Sister Chromatids: Identical copies formed after DNA replication.

• Diploid (2N): Two sets of chromosomes.

• Haploid (N): One set of chromosomes (gametes).

The Cell Cycle and Mitosis

The cell cycle consists of four phases: G1, S, G2, and M. Mitosis produces two identical diploid daughter cells, maintaining chromosome number.

• Interphase: G1 (growth), S (DNA synthesis), G2 (preparation for division).

• Mitosis: Division of the nucleus and cytoplasm.

Meiosis and Genetic Variation

Meiosis involves one DNA duplication and two cell divisions, resulting in four genetically distinct haploid gametes. It explains Mendel's laws at the chromosomal level.

• Meiosis I: Homologous chromosomes separate (reduction division).

• Meiosis II: Sister chromatids separate (equational division).

• Genetic Variation: Independent assortment and crossing over during prophase I increase genetic diversity.

Modifications to Mendelian Genetics

Simple Mendelian Traits vs. Real World Complexity

Mendel studied monogenic traits with two alleles and complete dominance. Most traits in nature are more complex, involving:

• Sex linkage

• Incomplete dominance

• Multiple alleles

• Codominance

• Lethal alleles

• Conditional alleles

• Sex modification

• Penetrance and expressivity

• Gene interaction

• Genetic linkage

Sex Linkage and the White-Eyed Fruit Fly

T.H. Morgan's experiments with Drosophila melanogaster demonstrated sex linkage, mapping the white gene to the X chromosome. Males (XY) need only one mutant allele to express the trait, while females (XX) need two.

• X-linked Trait: Inheritance pattern differs between sexes.

• Reciprocal Crosses: Showed that the source of the allele (mother or father) affects the outcome.

Modifications to Simple Mendelian Rules

Incomplete Dominance

In incomplete dominance, heterozygotes display a phenotype intermediate between the two homozygotes. Example: flower color in snapdragons.

• Genetic Ratio: 1:2:1 for both genotype and phenotype.

• Molecular Explanation: One copy of the dominant allele does not produce enough protein for full function.

Multiple Alleles

Most genes have more than two alleles in the population. Example: rabbit coat color gene (C, cch, ch, c).

• Dominance Hierarchy: C > cch > ch > c

• Molecular Explanation: Different alleles produce enzymes with varying activity or sensitivity.

Codominance

In codominance, both alleles in a heterozygote are fully expressed. Example: human blood type (IA, IB, i).

• Blood Type AB: Both A and B antigens are present.

• Molecular Explanation: Different alleles encode enzymes that add distinct sugars to red blood cells.

Lethal Alleles

Lethal alleles cause death when present in certain genotypes, altering expected Mendelian ratios. Example: yellow coat color in mice (AY AY is lethal).

• Genetic Ratio: 2:1 instead of 3:1.

• Molecular Explanation: Essential protein function is lost.

Pleiotropy

Pleiotropy occurs when a single gene affects multiple phenotypes. Example: white fur and deafness in cats.

Conditional Alleles

Conditional alleles express mutant phenotypes only under certain conditions, such as temperature-sensitive mutations.

• Example: Himalayan rabbit and Siamese cat coat color.

Sex-Limited and Sex-Influenced Traits

Some traits are only expressed in one sex (sex-limited) or are influenced by sex (sex-influenced).

• Sex-Limited: Feathering phenotype in male birds.

• Sex-Influenced: Bearded phenotype behaves differently in males and females.

Penetrance and Expressivity

Penetrance refers to the proportion of individuals with a genotype that show the expected phenotype. Expressivity describes the severity of the phenotype.

• Incomplete Penetrance: Not all individuals with the genotype show the phenotype.

• Variable Expressivity: Phenotype varies in severity among individuals.

• Example: Polydactyly in humans.

Summary Table: Modifications to Mendelian Inheritance

Modification	Genetic Behavior	Example
Sex Linkage	Trait linked to sex chromosomes	White eyes in Drosophila
Incomplete Dominance	Intermediate phenotype in heterozygotes	Snapdragon flower color
Multiple Alleles	More than two alleles per gene	Rabbit coat color, human blood type
Codominance	Both alleles fully expressed	Blood type AB
Lethal Alleles	Some genotypes are lethal	Yellow mice
Pleiotropy	One gene affects multiple traits	White fur and deafness in cats
Conditional Alleles	Phenotype depends on environment	Siamese cat coat color
Sex-Limited/Influenced	Trait only in one sex or influenced by sex	Feathering in birds, bearded phenotype
Penetrance/Expressivity	Variation in phenotype expression	Polydactyly in humans

Key Equations

• Mendelian Ratio (Monohybrid Cross): $3:1$ (phenotype), $1:2:1$ (genotype)

• Dihybrid Cross Ratio: $9:3:3:1$ (phenotype)

• Penetrance Calculation: $\text{Penetrance} = \frac{\text{Number showing phenotype}}{\text{Total with genotype}} \times 100\%$

Conclusion

Mendelian genetics provides the foundation for understanding heredity, but real-world traits often display more complex patterns due to modifications such as sex linkage, incomplete dominance, multiple alleles, codominance, lethal alleles, pleiotropy, conditional alleles, sex modification, penetrance, expressivity, gene interaction, and genetic linkage. Mastery of these concepts is essential for advanced study in genetics.