Difference between Missense and Nonsense Mutation

Genetic mutations are the permanent alterations to the nucleotide sequence of a gene. Mostly, these mutations are advantageous enabling evolution, generating new desirable traits. Some could be problematic mutations and result in abnormalities.

Based on where it occurs and where it can change the function of essential proteins, the gene variants can have different effects on health. On the basis of the effect on DNA sequence or the encoded protein, mutations can be classified. The types of variants are as follows:

  • Insertion
  • Deletion
  • Substitution
  • Deletion-insertion
  • Inversion
  • Duplication
  • Repeat expansion
  • Frameshift

Substitution – This variant type substitutes or replaces a nucleotide with another. Furthermore, based on the effect it has on the production of proteins from the changed gene, substitution variants can be classified as:

  • Missense
  • Nonsense

The nonsense and missense mutations vary in the fact that the missense mutation inserts a different codon other than the stop codon to the gene sequence, resulting in the non-synonymous amino acid in the polypeptide chain. On the other hand, the nonsense mutation inserts a stop codon into the gene sequence, resulting in premature chain termination.

Missense Mutation

  • This substitution variant type is when the change in nucleotide leads to the replacement of one amino acid or protein building block with another in the protein composed of the gene
  • Modification in amino acids could be essential in the functioning of a protein
  • Some of these mutations cause amino acids to be incorporated, causing the protein to be more effective

Nonsense Mutation

  • This substitution variant type is where rather than inducing a change in the amino acid, the modified DNA sequence causes a stop signal which signals the cell to prematurely stop the building of a protein – the premature termination of translation.
  • It leads to a shortened protein that does not function properly or gets disintegrated or non-functional.
  • In other words, this point mutation introduces a premature stop codon in the mRNA sequence; wherein a single nucleotide alteration results in the introduction of a stop codon. When this occurs, it terminates the translation without finishing the complete translation, resulting in the protein becoming shortened abnormally.

Key Difference between Missense and Nonsense Mutation

The table below depicts the difference between Missense and Nonsense Mutation.

Missense Mutation

Nonsense Mutation

What is it?

Single base-pair substitutions alter the genetic code, thus producing amino acids different from the normal amino acids at that location

This alteration causes a sense codon corresponding to one of the 20 amino acids given by the genetic code to be altered to a chain-termination codon

Type of codon introduced

Distinct codon

Stop codon at the mutation site

Is a different amino acid substituted?

Yes

No

Are proteins produced functional?

It could be non-functional, functional or can have a different function from the actual protein

Usually non-functional

What is the outcome?

Distinct amino acids – nonconservative or conservative.

Results in different amino acid sequence

At the mutation site, it leads to premature chain termination.

Results in a shorter and incomplete protein product

Resultant protein

Non-conserved or conserved protein

Truncated protein

Resultant abnormalities

Epidermolysis bullosa, sickle cell disease

Beta thalassemia, cystic fibrosis

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