Question

You have isolated three sequence variants of a fruit fly gene that allows normal body coloration to develop. Below are sequences of the protein-coding region of DNA; these have been reduced in length for clarity. You will need to translate these coding strands to answer this question.

• One sequence was isolated from the study has a nonsense mutation, which leads to dark body coloration. (loss-of-function )
• A second sequence is from a mutant with a missense mutation that leads to a medium body coloration (a hypomorph).
• A third sequence below has a frame-shift, which also leads to dark body coloration (loss-of-function)
• A fourth sequence is from a fly with normal body color. (silent mutation)

Wild-type   ATG TAT AAA CCC TGG ACG GTT CGT TAG

Mutant 1    ATG TAA AAC CCT GGA CGG TTC GTT AGA

Mutant 2    ATG TAT GAA CCC TGG ACG GTT CGT TAG

Mutant 3    ATG TAT GAA CCC TGA ACG GTT CGT TAG

Mutant 4    ATG TAC AAA CCC TGG ACG GTT CGT TAG

For each mutant, Identify the type of mutation (nonsense, missense, frameshift, normal) along with if its a loss of function, hypomorph, or silent.

Answer 1

Wild-type: ATG TAT AAA CCC TGG ACG GTT CGT TAG
Protein sequence: MYKPWTVR

Mutant 1: ATG TAA AAC CCT GGA CGG TTC GTT AGA
Protein sequence: M.
Type of mutation: Deletion of T at the 3rd base position of the second codon results in the formation of an in-frame premature termination codon (Nonsense and frameshift)
Effect of the mutation: A truncated nonfunctional protein is produced (Loss of function)

Mutant 2: ATG TAT GAA CCC TGG ACG GTT CGT TAG
Protein sequence: MYEPWTVR.
Type of mutation: Nonsynonymous mutation (Lys to Glu) (Missense mutation)
Effect of the mutation: Protein activity will be reduced/lost (Loss of function)

Mutant 3: ATG TAT GAA CCC TGA ACG GTT CGT TAG
Protein sequence: MYEP.
Type of mutation: Replacement of A at the 1st base position of the 3rd codon (Missense)
Replacement of G at the 3rd base position of the 5th codon results in the formation of an in-frame premature termination codon (Nonsense)
Effect of the mutation: A truncated nonfunctional protein is produced (Loss of function)

Mutant 4: ATG TAC AAA CCC TGG ACG GTT CGT TAG
Protein sequence: MYKPWTVR.
Type of mutation: Silent mutations
Effect of the mutation: No change in protein function (Silent)