Notes on Degrees of Dominance, Pleiotropy, and Multiple Alleles

Degrees of Dominance (Chapter 14.2 - 14.3)

Degrees of dominance describe the relationships between alleles and how they are expressed in the phenotype, particularly in heterozygous individuals.

Complete Dominance:
- Occurs when the phenotype of the heterozygote is identical to the phenotype of the dominant homozygote.
- One allele completely masks the expression of the other allele in the heterozygote.
Codominance:
- Occurs when two dominant alleles affect the phenotype in separate, distinguishable ways.
- Both alleles are fully expressed in the heterozygote, resulting in a phenotype that shows characteristics of both homozygous parents.
Incomplete Dominance:
- Occurs when the phenotype of $F_1$ hybrids is somewhere between the phenotypes of the two parental varieties.
- Neither allele is completely dominant, leading to an intermediate phenotype in heterozygotes.
Impact on Probabilities:
- The presence of codominance or incomplete dominance changes the probability of the phenotype being the same as the genotype. In these cases, each genotype often correlates with a distinct phenotype.
Example: Incomplete Dominance in Tulips
- Consider crossing two pink tulips that are heterozygous for the red allele (R) and white allele (W).
- The alleles are:
  - $R$ : Red allele
  - $W$ : White allele
  - $RW$ : Pink phenotype (intermediate)
- Punnett Square for $RW \times RW$ :
  R
  W
  R
  RR
  RW
  W
  RW
  WW
- Genotype Probability:
  - $1/4$ Red (RR)
  - $2/4$ Pink (RW)
  - $1/4$ White (WW)
  - Ratio: $1:2:1$
- Phenotype Probability:
  - $1/4$ Red
  - $2/4$ Pink
  - $1/4$ White
  - Ratio: $1:2:1$

	R	W
R	RR	RW
W	RW	WW

Pleiotropy: One Gene, Multiple Effects

Definition of Pleiotropy: A phenomenon where one gene has multiple phenotypic effects.
Impact of Genetic Mistakes: The question "What if the primary structure (amino acid sequence) changes due to a genetic mistake?" introduces a key concept related to how a single gene mutation can ripple through an organism's biology.
Sickle-Cell Disease: A Classic Example of Pleiotropy
- Genetic Basis: Sickle-cell disease arises from a single nucleotide substitution in the gene encoding the beta-globin subunit of hemoglobin.
  - This changes a specific amino acid in the primary structure:
    - Normal: Position 6 is Glutamic Acid (Glu).
    - Sickle-cell: Position 6 is Valine (Val).
    - Primary Structure Comparison:
      - Normal: Val-His-Leu-Thr-Pro-Glu-Glu…
      - Sickle-cell: Val-His-Leu-Thr-Pro-Val-Glu…
- Molecular and Cellular Consequences:
  - Normal Hemoglobin:
    - Normal B subunit structure.
    - Quaternary structure: Normal hemoglobin; proteins do not associate with one another, allowing each to carry oxygen efficiently.
    - Red Blood Cell (RBC) Shape: Normal biconcave disc.
  - Sickle-Cell Hemoglobin:
    - Sickle-cell B subunit structure.
    - Quaternary structure: Under low oxygen conditions (Low $O_2$ ), the altered hemoglobin proteins aggregate into long fibers. This significantly reduces the capacity to carry oxygen.
    - Red Blood Cell (RBC) Shape: The aggregated hemoglobin fibers distort the red blood cells into a characteristic sickle shape (sickled red blood cells), visible at $5 \mu m$ .
- Phenotypic Effects (Multiple Effects from One Gene):
  - (a) Homozygote with sickle-cell disease (two sickle-cell alleles):
    - Symptoms: Weakness, anemia (due to destruction of sickled cells), pain and fever (from blockages), and severe organ damage (due to impaired blood flow and oxygen delivery).
    - Under low oxygen, all hemoglobin forms fibers, leading to widespread sickling.
  - (b) Heterozygote with sickle-cell trait (one sickle-cell allele, one normal allele):
    - Symptoms: Typically asymptomatic but may show some symptoms when blood oxygen is very low (e.g., at high altitudes or during intense exercise).
    - Beneficial Effect: A significant reduction of malaria symptoms. This provides a strong heterozygote advantage in malaria-prone regions.
    - Under very low oxygen, both sickle-cell and normal hemoglobin proteins are present. Some sickling can occur, but it is less severe than in homozygotes.
- Dominance in Sickle-Cell Trait: Sickle cell disease showcases a complex pattern of dominance:
  - At the organismal level: It generally exhibits incomplete dominance, as heterozygotes are typically healthy but can show symptoms under extreme conditions.
  - At the cellular level: Regarding cell shape, it shows incomplete dominance, as some sickling occurs in heterozygotes under low oxygen.
  - At the molecular level: It exhibits codominance, as both normal ( $Hb^A$ ) and sickle ( $Hb^S$ ) hemoglobin proteins are produced in heterozygotes.

Multiple Alleles and ABO Blood Types

Multiple Alleles:
- While an individual can only have two alleles for a given gene, multiple alleles refer to the existence of more than two possible alleles for that gene within a population (e.g., $I^A$ , $I^B$ , $i$ for ABO blood type).
ABO Blood Type System:
- A classic example of a gene with multiple alleles and codominance.
- There are three alleles for the ABO blood group gene: $I^A$ , $I^B$ , and $i$ (or $I^O$ ).
- Allele Interactions:
  - $I^A$ and $I^B$ alleles are codominant. They both result in the expression of distinct carbohydrate antigens (A and B, respectively) on the surface of red blood cells.
  - The $i$ allele (or $I^O$ ) is recessive to both $I^A$ and $I^B$ . Individuals with genotype $ii$ have blood type O, meaning they do not produce A or B antigens.
Rh Factor Gene:
- A second gene that determines an additional blood group antigen, the Rh factor.
- Alleles: Two alleles, $Rh+$ and $Rh-$ .
- Expression:
  - The $Rh+$ allele codes for a specific protein found on the surface of red blood cells.
  - The $Rh-$ allele does not code for this protein.
- Dominance: $Rh+$ is dominant to $Rh-$ . Therefore, individuals with genotypes $Rh+/Rh+$ or $Rh+/Rh-$ are Rh-positive, while only individuals with genotype $Rh-/Rh-$ are Rh-negative.