Chromosomal Theory of Inheritance

Lecture Date: 02-09-2026
Instructor: Maya Capelson
Focus topics: Chromosomal theory of heredity, sex linkage, and sex determination.

Genes and their inheritance patterns are linked to the meiotic movement of chromosomes.

Definition: The 20th-century theory of inheritance that asserts that units of inheritance (genes) are located on chromosomes.
Key Contributors:
- Walter Sutton and Theodor Boveri: Linked the meiotic behavior of chromosomes to Mendel’s laws of heredity.
- Thomas Hunt Morgan and Eleanor Carothers: Advanced the understanding of inheritance through model organisms.

First Law (Law of Segregation):
- Alleles separate during gamete formation.
- Homologous chromosomes segregate to produce haploid gametes that fuse during fertilization to form diploid offspring.
- Visual illustration:
  - Example Genotype: AaBb
  - Gametes formed include: A, a, B, b.
Second Law (Law of Independent Assortment):
- Alleles of different genes assort into gametes independently of one another.
- Non-homologous chromosomes segregate independently during meiosis.
- Visual illustration:
  - Example Genotype: AaBb and potential gametes considering independent assortment.

Mitosis:
- Results in two identical daughter cells; does not involve separation of homologous chromosomes.
Meiosis:
- Results in four genetically diverse gametes, emphasizes the segregation of alleles.

Aneuploidy:
- Abnormal changes in chromosome number result in phenotypic consequences.
- Examples of conditions:
  - Trisomy: Presence of an extra chromosome.
  - Triploidy: Presence of an entire extra set of chromosomes.
- Non-disjunction is the failure of chromosomes to separate properly during meiosis.

Deletion:
- Loss of a chromosome segment can cause phenotypic changes.
- Example: Deletion of a genetic segment A, B, C resulting in A, B, D, E, F.
Duplication:
- A segment is duplicated, resulting in potential evolutionary advantages.
- Example: A, B, C, D, E results in A, B, C, D, E, D, E, F.
Inversion:
- A segment breaks off and reattaches in reverse order.
- While it doesn't lead to a loss of genetic material, it can affect fertility due to improper pairing during meiosis.
Translocation:
- Exchange of segments between non-homologous chromosomes.
- Implications include cancer risk, particularly in leukemia.

Chromosomal Basis of Sex Determination:
- The sex of an organism is often determined by the arrangement of sex chromosomes.
- Humans:
  - XX denotes a female; XY denotes a male.
  - The SRY gene promotes testis formation in male fetuses.
- Non-Disjunction Effects:
  - Aneuploidy in sex chromosomes causes conditions like Turner Syndrome (X0), Klinefelter Syndrome (XXY), and more.

Turner Syndrome (X0):
- Phenotypically female; underdeveloped female characteristics; often sterile.
Poly-X Syndrome (XXX):
- Phenotypically female; taller than average; typically fewer other abnormalities.
Klinefelter Syndrome (XXY):
- Phenotypically male; taller; often experiences fertility issues.
Jacob Syndrome (XYY):
- Phenotypically male; often taller; may experience reduced fertility.

Drosophila (Fruit Flies):
- Females have two X chromosomes, while males have one X and one Y.
- The presence of a Y chromosome does not directly determine sex; rather, it is the number of X chromosomes that matters.
- Conditions that are lethal in Drosophila (like XXX) manifest differently in humans (where individuals with XXX are often phenotypically normal).

X-Chromosome Aneuploidy:
- Mechanism to equalize the gene dosage of X chromosomes in males and females.
- Females (XX) randomly inactivate one of their X chromosomes, creating a Barr body.
- This creates a mosaic of cells with different X chromosomes active.

Different species have evolved unique strategies for dosage compensation, adjusting gene expression levels based on sex chromosome composition.

Establishing Drosophila as a Genetic Model:
- Thomas Morgan used Drosophila melanogaster to illustrate sex-linked traits.
- Key observations:
  - Mutant male fly with white eyes crossed with red-eyed female yielded all red-eyed F1 offspring, indicating red was dominant.
Inheritance Patterns in Drosophila:
- In F2 generation, the female flies were all red-eyed, while the males showed a 1:1 ratio of red to white phenotypes.
- This deviation from expected ratios led Morgan to hypothesize that the white gene is located on the X chromosome.

Gene Naming Conventions:
- Gene names are derived from the associated mutant phenotype (e.g., white).
- Recessive mutations are indicated with lowercase letters (e.g., w for white), whereas wild-type alleles are marked with a superscript + (e.g., w+).
Genotypes of Morgan’s Flies:
- Red-eyed female: w+(X)/w+(X)
- White-eyed male: w-(X)/Y
- Red-eyed male: w+(X)/Y
- F1 and F2 progenies exhibit segregation of red and white eye colors, conforming to sex-linked inheritance patterns.

Morgan's work illustrated that sex-linked traits, specifically eye color, could not be explained by autosomal inheritance patterns.
These initial findings laid the groundwork for understanding sex-linked inheritance and its implications in genetics.