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Question 3. Human haemoglobin is a complex protein molecule made up of four poly-peptides joined to...

Question 3.

Human haemoglobin is a complex protein molecule made up of four poly-peptides joined to an iron-containing haem group. In normal human adult haemoglobin, haemoglobin A, or HbA, two kinds of polypeptides designated as alpha and beta are found. Two identical alpha and two identical beta chains plus the haem group make up each molecule of haemoglobin A. Haemoglobin S, or HbS, is a haemoglobin variant occurring in individuals affected with the heritable disorder sickle cell anaemia. A comparison of the amino acid sequences of the polypeptides in haemoglobins A and S indicates that the alpha chains in the two molecules are identical, but that the beta chains differ in a single interior amino acid.

a.   How many of genes are necessary for the synthesis of haemoglobin S in an adult who is homozygous for the S allele?

b.   Assuming that the gene for the beta chain of HbS arose from the gene for the beta chain of HbA through a single mutation, what general type of mutation was most likely responsible?

c.   The difference between the beta chains of haemoglobin S and A is restricted to the sixth amino acid from the amino (-NH2) end of the polypeptide. In haemoglobin S, the amino acid at the site is valine and in haemoglobin A it is glutamic acid. From your knowledge of the genetic code (and with reference to the genetic code) what can you deduce about the specific (and simplest) base alteration in the beta polypeptide that would produce the amino acid substitution?

Solutions

Expert Solution

Please find the answers below:

Answer a: According to the information, four peptides are involved in structural composition of hemoglobin. However, it is important to note here that the sickle-cell mutant will also contain same number of polypeptides. Although a single gene is capable of generating the requisite amount of any polypeptide, a homozygous individual will have two copies of this gene over each of the chromosome. However, only a single polypeptide will be synthesized during translation. Hence, two copies of the gene would be present.

Answer b: The substitution of a single nitrogenous base in the nucleotide sequence refers to base-substitution type of mutation.

Answer c: It is a very well known fact that each codon encodes for a specific amino acid. Thus, the sickle-cell trait holds the same fact that a codon encodes for the normal amino acid. However, the single base pair substitution leads to change in identity of the codon and hence the nature of amino acid changes from glutamic acid to valine. This substitution leads to onset of pathology as sickel-cell trait.


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