Question

In HbS, the human hemoglobin found in individuals with sickle-cell anemia, glutamic acid at position 6 in the beta chain is replaced by valine. (a) List the two codons for glutamic acid and the four codons for valine. (b) Show that one of the glutamic acid codons can be converted to a valine codon by a single substitution mutation, that is by changing one letter in one codon.

Short answer

How can a single substitution mutation convert a glutamic acid codon to a valine codon? Answer: The amino acids involved in the mutation causing sickle-cell anemia are glutamic acid and valine. Glutamic acid is represented by the codons GAA and GAG, while valine is represented by the codons GUU, GUC, GUA, and GUG. A single substitution mutation can convert a glutamic acid codon to a valine codon in the following ways: Changing GAA to GUA (changing A to U) or changing GAG to GUC (changing G to C) or changing GAG to GUG (changing G to U).

Step-by-step solution

List the codons for glutamic acid and valine

To solve part (a) of the exercise, refer to a genetic code chart to find the codons that correspond to the amino acids glutamic acid and valine. The genetic code consists of 64 possible three-nucleotide sequences or codons. Each codon corresponds to a specific amino acid. From the genetic code chart, we can find the following: For glutamic acid (Glu), two codons are available: GAA and GAG. For valine (Val), four codons are available: GUU, GUC, GUA, and GUG.

Identify the single substitution mutation converting a glutamic acid codon to a valine codon

Now, we will look for a single substitution mutation that could change one of the glutamic acid codons (GAA or GAG) into one of the valine codons (GUU, GUC, GUA, or GUG). We can do this by systematically comparing each glutamic acid codon to each valine codon and counting the number of substitutions needed to convert one into the other: - GAA to GUU: 2 substitutions needed (GAA -> GUU) - GAA to GUC: 2 substitutions needed (GAA -> GUC) - GAA to GUA: 1 substitution needed (GAA -> GUA) - GAA to GUG: 2 substitutions needed (GAA -> GUG) - GAG to GUU: 3 substitutions needed (GAG -> GEU -> GCU -> GUU) - GAG to GUC: 1 substitution needed (GAG -> GUC) - GAG to GUA: 2 substitutions needed (GAG -> GAA -> GUA) - GAG to GUG: 1 substitution needed (GAG -> GUG) Since we are looking for a single substitution mutation, the viable mutation is changing GAA to GUA (changing A to U) or GAG to GUC (changing G to C) or GAG to GUG (changing G to U). Each of these mutations requires only a single nucleotide change and results in a valine codon being formed from a glutamic acid codon.

Key concepts

Codons

Codons are the foundational blocks in the genetic code, composed of three nucleotide sequences that correspond to specific amino acids. The human DNA transcript is a long series of these triplets, each encoding a specific instruction for producing proteins.

• A codon can either start or terminate the synthesis of proteins or represent one of the 20 amino acids used in proteins.
• The translation of DNA sequences into proteins requires accuracy in reading these codons, as any mutation might alter the type of protein synthesized.

In the context of genes like the one responsible for hemoglobin, the function of each codon is crucial. Understanding the interplay between codons and mutations is essential for topics such as genetic diseases, including sickle-cell anemia.

Glutamic Acid

Glutamic acid is one of the 20 amino acids coded by DNA and plays a pivotal role in the function and structure of many proteins. It is essential for processes like metabolism and neurotransmission in the human body.

• In the genetic code, glutamic acid is represented by the codons GAA and GAG.
• These codes instruct cells to add glutamic acid into the growing protein chain.

A mutation in these codons can lead to significant health implications, as seen in the case of sickle-cell anemia, where a substitution in the DNA sequence results in the production of a faulty hemoglobin molecule.

Valine

Valine is another amino acid critical for maintaining protein functionality, encoded by four different codons: GUU, GUC, GUA, and GUG. This versatility allows valine to substitute more readily with other amino acids, sometimes due to mutations.

• Being a nonpolar amino acid, valine is hydrophobic, impacting the folding and structure of proteins.
• In hemoglobin molecules, the presence of valine instead of glutamic acid alters its behavior, affecting oxygen transport.

This substitution in the genetic code leads to the formation of a sickled shape in red blood cells, which is characteristic of sickle-cell anemia.

Sickle-Cell Anemia

Sickle-cell anemia is a genetic disorder caused by a mutation in the hemoglobin gene, specifically in the codons for glutamic acid. When the codon for glutamic acid is replaced with valine, the hemoglobin molecules form an abnormal structure.

• This leads to the development of erythrocytes with a sickle shape, affecting their ability to transport oxygen efficiently.
• These abnormally shaped cells can clog blood vessels, causing pain and complications in individuals with the disease.

A single mutation in the DNA sequence, by altering a codon from glutamic acid to one of valine, is pivotal in the onset of this ailment.

Amino Acids

Amino acids are organic compounds that combine to form proteins, which are crucial for nearly all functions within an organism. There are 20 amino acids that cells use to construct proteins, each coded by one or more specific codons.

• They play essential roles, such as forming enzymes that speed up chemical reactions, and in building tissues like muscles and ligaments.
• The unique sequence of amino acids dictates the 3D structure and function of proteins.

In genetic mutations, such as those causing sickle-cell anemia, changes in the nucleotide sequence of DNA can alter which amino acids are incorporated into a protein, thus affecting its function and potentially leading to disease.