Describe the molecular basis of multiple alleles giving a suitable example

In classical Mendelian genetics, a gene usually has only two alleles: one dominant and one recessive. However, in real-life situations, many genes exist in more than two alternative forms. These are called multiple alleles. So, when more than two alleles exist for the same gene locus within a population, it is called the multiple allelic condition.

Although a diploid organism, like a human, carries only two alleles at a time, multiple alleles refer to the presence of more than two allelic forms in the population for the same gene. The molecular basis of multiple alleles lies in the specific changes in DNA sequence that result in structurally or functionally different proteins from the same gene

Molecular Basis of Multiple Alleles

The molecular basis of multiple alleles lies in slight differences in the DNA sequence of the gene. These mutations in the nucleotide sequence of the same gene lead to the formation of different allelic forms. These differences can be:
  • A single base change (point mutation)
  • An insertion or deletion of nucleotides
  • Sometimes substitution of amino acids in the protein encoded.
These changes do not create entirely new genes, but they modify the gene's coding sequence, leading to the formation of functionally different proteins or enzymes from the same gene. These different versions are inherited in various combinations and result in different phenotypes.

Each allele of such a gene produces a slightly altered version of the same protein, which interacts differently with substrates or targets. Thus, the molecular variation in the gene sequence is the root cause of multiple phenotypes for a single trait.

Example: ABO Blood Group in Humans

The best example of multiple alleles in humans is the ABO blood group system, discovered by Karl Landsteiner in 1900. This trait is controlled by a single gene called single gene or I gene (isoagglutinin gene) located on chromosome number 9. This gene has three allelic forms:
  1. IA allele – produces A antigen on red blood cells.
  2. IB allele – produces B antigen on red blood cells.
  3. i allele – produces no antigen (recessive).
At the molecular level:
  • The IA and IB alleles code for slightly different glycosyltransferase enzymes that add different sugar molecules to the surface of red blood cells.
  • The IA allele adds N-acetylgalactosamine, which forms the A antigen.
  • The IB allele adds galactose, which forms the B antigen.
  • The i allele has a mutation (frameshift), so it produces no functional enzyme and no antigen is formed.
So, the three alleles interact as follows:
  • IA and IB are codominant, both are expressed when present together (as in AB blood group).
  • i is recessive to both IA and IB.

Genotypes and Phenotypes in ABO System:

This system shows both codominance (IA and IB) and multiple allelism (three alleles).






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