Multiple alleles Knowledge-Based Study

Study notes

1. What Are Multiple Alleles?

   In classical Mendelian genetics, traits are typically described as being governed by a single gene with only two alternative alleles (such as dominant A and recessive a). However, in natural populations, many genes exist in more than two allelic forms. This phenomenon is known as multiple allelism.

   Key Principles

   • Population vs. Individual: Although a gene can have three, four, or dozens of different alleles within a whole population, any normal diploid individual carries at most two alleles for that gene—one inherited from each parent on homologous chromosomes.
   • Origin: Multiple alleles arise through different mutations occurring at the same genetic locus over evolutionary time.
   • Dominance Hierarchies: Unlike simple complete dominance between two forms, multiple alleles can display varied relationships among themselves, including complete dominance series, codominance, or incomplete dominance.

   The ABO Gene Locus

   One of the most familiar examples of multiple alleles in humans is the ABO blood group system, which determines the carbohydrate antigens present on the surface of red blood cells.

   The Alleles Involved

   The ABO blood type is determined by three main alleles at the I locus:

   • $I^A$: Produces antigen A.
   • $I^B$: Produces antigen B.
   • $i$ (or $I^O$): Produces neither antigen (null/non-functional allele).

   Dominance Relationships and Phenotypes

   The relationship between these alleles combines complete dominance and codominance:

   • $I^A$ and $I^B$ are both completely dominant over $i$.
   • $I^A$ and $I^B$ are codominant with respect to each other; both are fully expressed simultaneously when present together.

   This results in four distinct phenotypes derived from six possible diploid genotypes:

   • Type A: Genotypes $I^A I^A$ or $I^A i$
   • Type B: Genotypes $I^B I^B$ or $I^B i$
   • Type AB: Genotype $I^A I^B$
   • Type O: Genotype $ii$

   A Graded Dominance Hierarchy

   In many organisms, multiple alleles establish a clear linear dominance series, often represented as an allelic series. A classic model is the C gene responsible for coat coloration in rabbits.

   The Four Alleles

   • $C$ (Agouti / Full color): Produces standard dark grayish-brown fur.
   • $c^{ch}$ (Chinchilla): Produces silver-gray fur due to reduced pigment production.
   • $c^h$ (Himalayan): Produces white fur across the body with pigmented (dark) extremities (nose, ears, paws, and tail) due to a temperature-sensitive enzyme.
   • $c$ (Albino): Produces completely white fur and unpigmented red eyes due to a completely inactive enzyme.

   Dominance Hierarchy

   These alleles follow a strict dominance hierarchy:

   $$C > c^{ch} > c^h > c$$

   Because $C$ is dominant over all other alleles, any genotype containing $C$ results in the agouti phenotype. Similarly, a rabbit must be homozygous $c c$ to exhibit the albino phenotype.

   Mathematical Determination of Genotypes

   When a gene locus has $n$ different alleles within a population, the total number of distinct diploid genotypes can be calculated using a standard formula.

   Formulas

   • Total Genotypes: $$\frac{n(n + 1)}{2}$$
   • Homozygous Genotypes: Exactly $n$ (one for each allele paired with itself).
   • Heterozygous Genotypes: $$\frac{n(n - 1)}{2}$$

   Number of Phenotypes

   The total number of phenotypes depends directly on the dominance relationships among the alleles:

   • Strict Dominance Hierarchy: If every allele is completely dominant over the subsequent alleles in the series, there are exactly $n$ observable phenotypes.
   • Presence of Codominance: If any pairs of alleles exhibit codominance or incomplete dominance, each codominant heterozygous combination forms an additional distinct phenotype (as seen in human blood group AB).