Question

Why is a frameshift missense mutation more likely to have a severe effect on phenotype than a nucleotide-pair substitution missense mutation in the same protein?

Answer 1

Explanation:

A single nucleotide-pair substitution missense mutation causes a change of a single amino acid into another. Aa a result, the produced protein will have an almost normal sequence except for one amino acid.

On the other hand, a frameshift mutation changes the Open Reading Frame (ORF) of the ribosome. The ribosome moves along the mRNA every three nucleotides (codons) and translates them into amino acids that will form the nascent protein. If there is a frameshift mutation (an insertion or deletion of a number of nucleotides not multiple of three) the ribosome will "read" the mRNA differently and will identify different codons than the wild-type sequence, so a large number of amino acids will be different in the mutated protein.