Question

Shown below is the anti-sense DNA sequence from a region of a gene that produces a specific protein. Mutations in this region of the gene cause a disease

CTT TTA TAG TAG ATA CCA CAA AGG

a. What is the mRNA strand that is transcribed from the DNA shown above?

b. What is the amino acid sequence that would be translated from the mRNA strand you determined in part 1?

c. If an individual has a G at position 15 (instead of A) the person will NOT have the disease. However, individuals with a C at position 14 (instead of T) do have the disease. Why would this be the case? Explain. Be sure to show that you understand how mutations affect protein structure.

d. What do you think will happen if you inserted or deleted a nucleotide from the original sequence given above? Explain.

e. Where do mutations in the original DNA come from? (i.e. what causes DNA

mutations?)

f. Are all mutations bad? Give and briefly explain an example of a mutation that provides an organism (bacteria or virus for example) with a survival advantage.

Answer 1

DNA sequence - CTT TTA TAG TAG ATA CCA CAA AGG

a) mRNA sequence - GAA AAU AUC AUC UAU GGU GUU UCC

b) Protein sequence - Glu-Asn-Ile-Ile-Tyr-Gly-Val-Ser

c) Changing the codon from ATA to ATG will cause a shift in the mRNA codon, making UAU to UAC. Both of these codons code for the polar amino acid Tyrosine, and hence this mutation does not lead to an amino-acid level change. This phenomenon persists for most of the other amino acids, where changing the 3rd base of a codon doesn’t affect the translated product. This is explained by the wobble hypothesis which was formulated by Francis Crick to explain codon degeneracy, where more than one codon codes for the same amino acid.

This holds true only for the third base. Changing the base at position 14 from T to C (the second base of the codon) makes the codon ACA, making the mRNA codon UGU, which codes for the amino acid cysteine. Hence a mutation at the 14^th position of this sequence leads to an amino acid change when translated, which can, in turn, perturb protein function by affecting its structure or activity.

d) An insertion or deletion of a base leads to frameshift mutations as the codons will now be out of frame from the original sequence, leading to a completely different or truncated product.

e) DNA mutations are caused by a wide range of factors, including copying errors, error-prone damage repair, and exposure to genotoxic agents, such as ionizing radiation and chemotherapy.

f) Mutations are neither good nor bad by nature. It is the environment which selects for or against a mutation. For example, if a mutation in a protein helps a bacteria to resist the activity of an antibiotic (antibiotic resistance), then those individuals that carry this mutation can outcompete the individuals that don’t carry it when under antibiotic selection. This mutated protein may not function as well as the normal protein, and hence the benefits may become apparent only when the bacteria are placed under antibiotic stress.

I hope this helps :)