Changes in DNA Modify the Amino Acid Sequences of Proteins

Given that codons in the DNA completely determine the nature and location of amino acids in proteins, it is easy to see that if, for any reason, codons in a gene change, this will result in the insertion of a different

Figure 4.8 A Protein Being Made from mRNA. A cartoon image of protein being made off of mRNA. The wavy line is the mRNA with a ribosome in the process of translating the sequence of triplet codons into their corresponding amino acids. Once the amino acids on the tRNA are attached to the growing protein chain, tRNAs without amino acids (on the left) are released. Then the ribosome moves over to the next codon and another tRNA with the complementary anticodon with its amino acid comes into the ribosome.

r growing protein chain

Figure 4.8 A Protein Being Made from mRNA. A cartoon image of protein being made off of mRNA. The wavy line is the mRNA with a ribosome in the process of translating the sequence of triplet codons into their corresponding amino acids. Once the amino acids on the tRNA are attached to the growing protein chain, tRNAs without amino acids (on the left) are released. Then the ribosome moves over to the next codon and another tRNA with the complementary anticodon with its amino acid comes into the ribosome.

amino acid in a protein. This is basically how mutations (changes in DNA base pairs) manifest their effects. Mutations will be studied in chapters 7 and 8. For now, let us just look at a few consequences of some base pair changes in the gene that codes for P-hemoglobin, one of the protein chains that constitute hemoglobin. We saw in chapter 3 that sickle-cell anemia is a very serious genetic disease. Its molecular basis is very well understood. Let us look at a small portion of the normal P-hemoglobin mRNA, which corresponds to codons 5-8:

The genetic code indicates that the translation product of this mRNA is the amino acid sequence

. . . Proline-Glutamic acid-Glutamic acid-Lysine. . . .

It turns out that this gene is mutated in sickle-cell anemia patients and produces a mRNA with the sequence

You will notice that the second base of the second codon (in bold) is now a U instead of an A. This change encodes a protein with the amino acid sequence

Thus, the amino acid valine replaces the glutamic acid found in normal hemoglobin, because GUG codes for valine while GAG codes for glutamic acid. This single amino-acid substitution occurred because the P-hemoglobin gene underwent a mutation, whereby an A-T base pair in the DNA was turned into a T-A base pair. In addition, this single change of an amino acid is responsible for all the problems associated with sickle-cell disease. This is because mutant P-hemoglobin, with this seemingly minor change from a glutamic acid to a valine, has a strong tendency to crystallize in red blood cells and sickle them, contrary to normal P-hemoglobin. Many genetic diseases are the result of such subtle mutational changes in codons.

Was this article helpful?

0 0

Post a comment