Question

When the amino acid sequences of insulin isolated from different organisms were determined, some differences were noted. For example, alanine was substituted for threonine, serine was substituted for glycine, and valine was substituted for isoleucine at corresponding positions in the protein. List the single-base changes that could occur in triplets to produce these amino acid changes.

Short answer

Answer: The single-base changes that can produce the amino acid substitutions are: - Threonine (Thr) to Alanine (Ala): Change A to G in the first position of the codon. - Glycine (Gly) to Serine (Ser): Change G to A in the first position for the codon GGC and change G to U in the second position for the codon GGC. - Isoleucine (Ile) to Valine (Val): Change A to G in the second position of the codon.

Step-by-step solution

List the codons for the original amino acids

The codons for the original amino acids are: - Threonine (Thr): ACA, ACC, ACG, ACT - Glycine (Gly): GGA, GGC, GGG, GGT - Isoleucine (Ile): ATA, ATC, ATT

List the codons for the substituted amino acids

The codons for the substituted amino acids are: - Alanine (Ala): GCA, GCC, GCG, GCT - Serine (Ser): UCA, UCC, UCG, UCT, AGC, AGU - Valine (Val): GUA, GUC, GUG, GUU

Identify the single-base changes between the original and substituted codons

Now, let's identify the single-base changes that can produce the amino acid substitutions: 1. Threonine (Thr) to Alanine (Ala): - ACA to GCA: Change A to G in the first position - ACC to GCC: Change A to G in the first position - ACG to GCG: Change A to G in the first position - ACT to GCT: Change A to G in the first position 2. Glycine (Gly) to Serine (Ser): - GGA to AGA: Change G to A in the first position (but this will lead to Arginine, so it's not valid) - GGC to AGC: Change G to A in the first position - GGG to AGG: Change G to A in the first position (but this will lead to Arginine, so it's not valid) - GGT to AGT: Change G to A in the first position (but this will lead to Serine in the new genetic code, so it's not valid) - GGA to UGA: Change G to U in the second position (but this will lead to a Stop codon, so it's not valid) - GGC to UGC: Change G to U in the second position - GGG to UGG: Change G to U in the second position (but this will lead to Tryptophan, so it's not valid) - GGT to UGT: Change G to U in the third position (but this will lead to Cysteine in the new genetic code, so it's not valid) 3. Isoleucine (Ile) to Valine (Val): - ATA to GUA: Change A to G in the second position - ATC to GUC: Change A to G in the second position - ATT to GUT: Change A to G in the second position (but this will lead to Valine in the new genetic code, so it's not valid) Thus, the single-base changes that can produce the amino acid substitutions are: - Threonine (Thr) to Alanine (Ala): Change A to G in the first position of the codon. - Glycine (Gly) to Serine (Ser): Change G to A in the first position for the codon GGC and change G to U in the second position for the codon GGC. - Isoleucine (Ile) to Valine (Val): Change A to G in the second position of the codon.

Key concepts

Codon Substitution

Understanding the concept of codon substitution is fundamental for students studying genetics. A codon is a sequence of three nucleotides in DNA or RNA that corresponds to a specific amino acid in a protein. As seen in the exercise, a single base change in a codon can result in the substitution of one amino acid for another in the protein structure.

For instance, the amino acid threonine, represented by the codons ACA, ACC, ACG, and ACT, can be changed to alanine (GCA, GCC, GCG, GCT) by substituting the first nucleotide adenine (A) with guanine (G). Such a substitution can alter the protein’s properties depending on the role of the amino acid within the protein's structure. Not all substitutions have the same effect. Some are synonymous and do not change the amino acid sequence, while others are nonsynonymous and can have significant effects, potentially even leading to diseases if they disrupt the protein's function.

To ensure clearer understanding, educators can focus on illustrating how the genetic code is degenerate—meaning multiple codons can code for the same amino acid—and explain the concept of substitution with visual aids such as charts and diagrams showing the before-and-after effects on the codon.

Amino Acid Sequences

The sequence of amino acids in a protein is like the order of words in a sentence; it determines the protein’s structure and function. In the exercise, we observe that slight alterations in the amino acid sequence, due to codon substitutions, can lead to different proteins, just as changing words can change the meaning of a sentence.

The difference between amino acid sequences in insulin from various organisms highlights evolutionary diversification. Even a single amino acid change, such as substituting serine for glycine, can have effects on the protein. It is important to note that the function of the resulting protein depends on the role of the changed amino acid; some may be in 'non-critical' areas where changes are more tolerable, while in other 'critical' areas, even a small change can render the protein nonfunctional.

When discussing amino acid sequences with students, the concept of protein domains and their specialized functions could also be emphasized. Use sequence alignment tools and phylogenetic trees to show how these sequences can inform us about evolutionary relationships among species.

Protein Structure

Proteins are more than just a chain of amino acids; they are complex structures that fold into specific three-dimensional shapes necessary for their function. The structure of a protein is crucial because it determines how the protein interacts with other molecules. There are four levels of protein structure:

• Primary structure: This is the linear sequence of amino acids in a protein.
• Secondary structure: This involves local arrangements of the protein chain into structures like α-helices and β-pleated sheets.
• Tertiary structure: This is the overall three-dimensional shape of the protein.
• Quaternary structure: This occurs when multiple protein chains come together to form a functional unit.

The simplest change in the primary structure, such as the substitutions given in the exercise, can lead to a change in the higher levels of structure and, thus, in the function of the protein. It's crucial to illustrate this cascade of impacts, from nucleotide to protein structure, to students. Using models and simulations can help students visualize how changes at the molecular level affect the full protein.