Question

Due to a recessive mutation in gene A, amino acid ‘Glu’ in position 25 of polypeptide A (the wild polypeptide) is replaced by ‘Ala’. Individuals who are homozygous for the mutant allele (aa) don’t have any phenotypic alterations. Based on this observation, which of the following IS TRUE?

	A.	The mutation has occurred in the promoter.
	B.	The mutation has occurred in one of the introns of the encoding gene.
	C.	The mutation was a base substitution in one of the exons of the gene, but has not changed the active site of the enzyme.
	D.	The mutation has occurred in a non-coding region of the genome.
	E.	The mutation was an insertion or deletion of a base pair in the second exon of the gene.

Answer 1

Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons. When they occur within exons they do not result in a change to the amino acid sequence of a protein (a "synonymous substitution"), in which case there is no change in phenotype. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations only occur within exons, and are not always silent mutations. Synonymous mutations can affect transcription, splicing, mRNA transport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent. The substrate specificity of the tRNA to the rare codon can affect the timing of translation, and in turn the co-translational folding of the protein. This is reflected in the codon usage bias that is observed in many species. Mutations that cause the altered codon to produce an amino acid with similar functionality (e.g. a mutation producing leucine instead of isoleucine) are often classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function.