Question

The change of a single base in the DNA sequence for normal hemoglobin can encode for the abnormal hemoglobin giving rise to sickle cell anemia. Which base in the codon for glu in DNA is replaced to give the codon(s) for val? (See Exercises 93 and \(109 .\) )

Short answer

In conclusion, the base substitution responsible for sickle cell anemia is the replacement of adenine (A) with uracil (U) in the second position of the Glu codon. This change results in the codons GAA (Glu) → GUA (Val) and GAG (Glu) → GUG (Val), which contribute to the formation of sickle-shaped blood cells.

Step-by-step solution

Identify codons for Glu and Val

The first step is to determine the codon(s) for glutamic acid (Glu) and valine (Val). Codons are sequences of three nucleotide bases in the DNA that code for specific amino acids. We can consult a genetic code table to identify the codons for Glu and Val. For Glu, the codons are: GAA and GAG For Val, the codons are: GUU, GUC, GUA, and GUG.

Identify the base substitution

Now, we need to identify which base substitution in the codon for Glu results in the codon(s) for Val. This will help us understand how a single base change can lead to sickle cell anemia. Looking at the codons for Glu (GAA and GAG) and Val (GUU, GUC, GUA, and GUG), we can see that changing the second base in the Glu codon from A to U results in a codon for Val. Specifically: GAA (Glu) → GUA (Val) GAG (Glu) → GUG (Val)

Identify the base that is replaced

Based on the analysis in Step 2, we can now determine which base in the codon for glutamic acid (Glu) is replaced to give the codon(s) for valine (Val) and subsequently gives rise to sickle cell anemia. The base that is replaced is the second base, adenine (A), with uracil (U) in the codon for Glu. This results in the following changes: GAA (Glu) → GUA (Val) GAG (Glu) → GUG (Val) In conclusion, the base substitution responsible for the production of abnormal hemoglobin in sickle cell anemia is the replacement of adenine (A) with uracil (U) in the second position of the Glu codon. This change results in the codon(s) for valine (Val), which contributes to the formation of sickle-shaped blood cells.

Key concepts

Genetic Code

The genetic code is essentially the blueprint for all living organisms, encoding instructions for the development, functioning, and reproduction of life. This code is comprised of nucleotide sequences in DNA, which are divided into units called codons. Each codon consists of three nucleotide bases. These codons are read sequentially, and each one corresponds to a specific amino acid or signal during protein synthesis.

The genetic dictionary is universal across almost all organisms, which is why a codon like AUG does not change its meaning from one species to another. This is key for understanding how DNA mutations can have widespread effects. Changes in just a single nucleotide can alter the genetic code, potentially leading to significant consequences, such as genetic diseases.

Nucleotide Base Substitution

Nucleotide base substitution, also known as a point mutation, occurs when a single nucleotide in the DNA sequence is replaced by a different base. These mutations might occur due to various factors such as errors during DNA replication or exposure to mutagens.

Typically, there are two main types of nucleotide base substitutions:

• Transition: This involves a purine being replaced by another purine (A to G, or vice versa) or a pyrimidine being replaced by another pyrimidine (C to T, or vice versa).
• Transversion: Here, a purine is substituted with a pyrimidine or vice versa (A to T or C, and G to T or C, and vice versa).

These substitutions can lead to various genetic outcomes. Sometimes, they may result in silent mutations where the protein remains unchanged. In other cases, they may cause missense mutations leading to a different amino acid in the protein that may alter its function. This is precisely what happens in sickle cell anemia.

Codon

Codons are the three-letter "words" of the genetic code that instruct cells on which amino acids to incorporate into a protein. These sequences of three nucleotides are indispensable for the translation of genetic information from DNA into functional proteins. Each of the 64 possible codons corresponds to a single amino acid or a stop signal in protein synthesis.

Interestingly, multiple codons can code for the same amino acid, offering a layer of redundancy. For instance, the amino acid valine is specified by the codons GUU, GUC, GUA, and GUG. This redundancy allows for some tolerance against minor mutations, as certain changes won't necessarily affect the protein's final structure.

In the context of sickle cell anemia, a single base change in the codon for glutamic acid (GAA or GAG) to that for valine (GUA or GUG) leads to the disease. Such changes emphasize the critical nature of codon accuracy in maintaining healthy biological functions.

Sickle Cell Anemia

Sickle cell anemia is a genetic disorder caused by a particular mutation in the DNA sequence of the hemoglobin gene. Hemoglobin is the protein in red blood cells responsible for oxygen transportation throughout the body.

In sickle cell anemia, a nucleotide base substitution occurs. The mutation replaces adenine with uracil in the DNA, changing the codon from one that specifies glutamic acid to one that specifies valine. This substitution alters the hemoglobin's structure, causing red blood cells to adopt a rigid, sickle-like shape. These misshapen cells can obstruct blood flow, leading to severe pain and potential organ damage.

• Individuals inherit sickle cell anemia in an autosomal recessive manner, meaning they need to inherit two copies of the mutant gene (one from each parent) to express the disease fully.
• Pain episodes, known as "crises," are common symptoms as these sickle-shaped cells block blood vessels.
• Early diagnosis and treatment are vital for managing symptoms and improving quality of life.

Through understanding these mutations, scientists and medical professionals work towards better treatment and potentially curing genetic disorders like sickle cell anemia.