Question

Effect of Single-Base Changes on Amino Acid Sequence Much important confirmatory evidence on the genetic code has come from assessing changes in the amino acid sequence of mutant proteins after a single base has been changed in the gene that encodes the protein. Which of the listed amino acid replacements would be consistent with the genetic code if the replacements were caused by a single base change? Which cannot be the result of a single- base mutation? Why? a. Phe \(\rightarrow\) Leu b. Lys \(\rightarrow\) Ala c. Ala \(\rightarrow\) Thr d. Phe \(\rightarrow\) Lys e. Ile \(\rightarrow\) Leu f. His \(\rightarrow\) Glu g. Pro \(\rightarrow\) Ser

Short answer

Phe→Leu, Ile→Leu, and Pro→Ser are possible single-base mutations. Lys→Ala, Ala→Thr, Phe→Lys, and His→Glu are not possible.

Step-by-step solution

Understanding the Problem

We need to determine whether each of the given amino acid replacements can occur due to a single-base mutation in the genetic code. Each amino acid is typically encoded by a three-nucleotide codon, and a single-base change can result in one nucleotide change in the codon.

Phe to Leu

Phenylalanine (Phe) is coded by UUU or UUC, and Leucine (Leu) is coded by CUU, CUC, CUA, CUG, UUA, or UUG. A single base change can transform UUU or UUC to UUA or UUG, which are both Leu. Hence, this replacement is possible through a single-base mutation.

Lys to Ala

Lysine (Lys) is coded by AAA or AAG, and Alanine (Ala) is coded by GCU, GCC, GCA, or GCG. None of the codons for Lys can be converted into codons for Ala via a single base change. Thus, this replacement is not possible through a single-base mutation.

Ala to Thr

Alanine (Ala) is coded by GCU, GCC, GCA, or GCG, and Threonine (Thr) is coded by ACU, ACC, ACA, or ACG. A single base change cannot convert any of the Ala codons into Thr codons. Therefore, this replacement is not possible through a single-base mutation.

Phe to Lys

Phenylalanine (Phe) is coded by UUU or UUC, while Lysine (Lys) is coded by AAA or AAG. A single base change cannot convert UUU or UUC to AAA or AAG. Hence, this replacement is not possible via a single-base mutation.

Ile to Leu

Isoleucine (Ile) is coded by AUU, AUC, or AUA, and Leucine (Leu) is coded by CUU, CUC, CUA, CUG, UUA, or UUG. A single base change can convert AUU to AUA, which is also Ile, to UUA or UUG which are both Leu. Thus, this replacement is possible through a single-base mutation.

His to Glu

Histidine (His) is coded by CAU or CAC, and Glutamic Acid (Glu) is coded by GAA or GAG. None of the His codons can be converted into Glu codons via a single base change. Thus, this replacement is not possible through a single-base mutation.

Pro to Ser

Proline (Pro) is coded by CCU, CCC, CCA, or CCG, and Serine (Ser) is coded by UCU, UCC, UCA, UCG, AGU, or AGC. A single base change can convert CCU, CCC, CCA, or CCG to UCU, UCC, UCA, or UCG, corresponding to Ser. Thus, this replacement is possible through a single-base mutation.

Key concepts

Single-Base Mutation

A single-base mutation, also known as a point mutation, occurs when one nucleotide in the DNA sequence is altered. This type of mutation can have significant effects on the corresponding protein because it may change the codon, which is a triplet of nucleotides that code for amino acids. When such a mutation happens, it can lead to several possibilities:

• Silent mutation: The mutation does not change the amino acid sequence of the protein. This is because the new codon, though different, still codes for the same amino acid due to redundancy in the genetic code.
• Missense mutation: This changes one amino acid in the sequence, potentially altering the protein's function if the new amino acid affects the protein's structure or activity.
• Nonsense mutation: This converts a codon into a stop codon, leading to a truncated and usually nonfunctional protein.

Understanding single-base mutations helps in analyzing genetic diseases and anticipating potential changes in protein function.

Amino Acid Sequence

The sequence of amino acids in a protein determines its structure and function. Proteins are made from chains of amino acids, folded into complex three-dimensional shapes. This sequence is dictated by the order of codons in the mRNA, which is transcribed from DNA.
A change in the DNA—such as a single-base mutation—may change the mRNA codons and thus the sequence of amino acids:

• Each amino acid is represented by one or more codons, and only certain codons can change to others with a single nucleotide modification.
• If the new amino acid has similar properties to the original, the impact on the protein might be minimal. If it has different properties, the protein's function could change significantly.

Thus, understanding how mutations affect amino acid sequences is crucial for fields like genetic engineering and medicine.

Codon Usage

Codons are triplets of nucleotides that represent specific amino acids in the genetic code. Each of the 20 amino acids can be encoded by one or more codons. This redundancy is known as 'codon degeneracy.' For example, the amino acid Leucine (Leu) can be encoded by six different codons: CUU, CUC, CUA, CUG, UUA, and UUG.
Single-base changes can thus switch one codon to another within this set and may or may not result in a different amino acid. This redundancy means that sometimes mutations do not alter the amino acid sequence at all.

• The codons for Any given amino acid are not randomly distributed but are linked to the evolutionary conservation and functional importance of proteins.
• Analyzing codon usage can provide insights into gene expression levels and the effects of mutations.

Recognizing this can assist scientists and researchers in predicting the outcomes of genetic mutations.

Mutation Analysis

Mutation analysis involves studying the changes in genetic sequences to determine their effects on the encoded protein. This process is useful for understanding how specific mutations lead to genetic diseases or alter biological functions.

• It includes assessing whether mutations such as single-base substitutions could be responsible for amino acid changes in proteins.
• Tools like DNA sequencing and bioinformatics databases help predict the implications of mutations on protein structure and function.
• By studying mutation patterns, researchers can better understand molecular mechanisms that underpin various conditions and develop targeted treatments.

Overall, mutation analysis is a powerful approach to linking genetic changes with biological outcomes, offering potential advancements in personalized medicine and therapies.