Question

1) List four outcomes that can result from a Base Substitution in the middle of a gene. For each outcome Explain:

A) What happens to the Amino Acid,

B) Why that happens to the Amino Acid, and

C) How it affects the protein.

2) DO NOT use terms such as “Missense”, “Nonsense”, “Frameshift”. DO NOT write the question in your answer. Do Not Give Examples using bases & codons. If you get a new Amino Acid, discuss side chains, categories, and intermolecular forces.

1.

2.

3.

4.

Answer 1

Solution

1. A mutation that leads to a nucleotide base substitution can have the following effects:

A) An amino acid codon has three bases. Any alterations on the first two bases guarantees a change in the amino acid. But a substitution in the third base called the 'wobble' base mostly would not result in an amino acid change.

B) The genetic code is degenerate. Degeneracy arises due to the third (wobble) base of a codon. One amino acid can have more than one codons say three codons. These three codons are similar in their first two bases but naturally have different nucleotides at the third base. So a change in the first two bases would lead to the incorporation of differnt amino acid but a mutation in the third base will lead to the same amino acid incorporation to the growing polypeptide chain.

C) If the amino acid incorporated is the same there would be no effect in the protein structure or function.

However, if there is an incorporation of a different amino acid, it might alter the structure, conformation and activity of the protein to various degrees.

• If the new amino acid is similar in properties to the replaced one, there might be no or lower degree of changes in protein
• if the new amino acid is vastly different in its properties (due to differences in side chain group) from the old one, the protein structure and function can get disrupted.

2. Let us assume there was an alteration and a new amino acid was incorporated. The amino acids can end up with different side chain groups (R - group). These side chain groups can be : (i) non-polar, neutral (ii) polar, neutral (iii) acidic, polar (iv) basic, polar. Non-polar neutral amino acids have pure hydrocarbon or aromatic side chains. Polar neutral amino acids have polar side chains but the zwitterion form of the amino acid is neutralized. Acidic polar amino acids produce a net negative charge as a contribution from its side chains. Basic polar amino acids have a net positive charge. If a polar amino acid is mutated to incorporate a non-polar side chain containing amino acid, the then hydrophilic surface interacting moiety will now try to fold to the interior of the protein, being a hydrophobic moiety. This will alter the overall folding conformation of the protein.

Also polar amino acids are capable of participating in intermolecular bond formations such as hydrogen bonds and disulfide bonds with other amino acids. The disulfide bonds give rise to multimeric proteins by joining monomers and helping sub-units to interact. If this polar amino acid gets replaced by a non-polar one who is incapable of forming such interactions will render the protein completely useless. The same thing will happen if a non-polar amino acid will mutate to a polar one. This will give rise to unnecessary interactions affecting protein folding and eventually its function. The charged groups of polar amino acids are responsible for ion-binding (such as Mg2+, Mn2+), interacting with substrate residues or drugs at the active sites of the enzymatic pockets. Any change in these crucial amino acids will also lead to faulty/altered proteins.