Mutations

When changes occur in nucleic acids, they are referred to as mutations. The agents that cause mutations are referred to as mutagens.

Many chemicals, such as some of the components of cigarette smoke and various chemical solvents such as benzene and carbon tetrachloride, can cause changes in nucleic acids when they come in contact.

Radiation, in the form of X-rays, gamma rays, and ultra-violet light, can also cause mutations to occur.

Some mutations are said to occur spontaneously. In the long run that may simply be a category that means that the mutation has occurred because of a cause which has not yet been figured out.

Photodimerization

The mechanism for one such mutation has been, at least, partly figured out and is illustrated in this diagram in a book by Caret and others. When two thymines are next to one another in DNA, ultra-violet light can cause the thymine residues to bond to one another and create what's called a thymine dimer.

Diagram of DNA with thymine dimers. [69057.jpg]

This error or mutation can be corrected by a repair enzyme, but the correction of this involves breaking the phosphate sugar ester bond, removing the affected nucleotides, and then either replacing them or repairing the thymines and putting them back. The process of removal and replacement will at times result in something other than two thymines to be put into place. Depending on what replaces the thymines, the mutation could be a substitution, a deletion or an addition.

Sickle Cell

Sickle cell anemia results from a substitution of valine for glutamic acid in the sixth position of the primary structure of the beta chain of hemoglobin. This, of course, is a consequence of changes in DNA.

Normal hemoglobin (beta chain)
Val-His-Leu-Thr-Pro-Glu-Glu-Lys-Ser-Ala-...

Sickle cell hemoglobin (beta chain)
Val-His-Leu-Thr-Pro-Val-Glu-Lys-Ser-Ala-...

In the exercise that follows you will work back from the protein to figure out what kinds of changes in DNA could result in the formation of sickle cell hemoglobin. Also, you will work forward from DNA to figure out the changes in protein that result from various mutations in DNA. (These questions are also in Exercise 17 in your workbook.)

Practice

Regarding the mutation that causes sickle cell anemia:

Use the first ten amino acids of the primary structure for normal human hemoglobin, to determine the mRNA and DNA base sequences that lead to it.

Use the first ten amino acids of the primary structure for sickle cell human hemoglobin, to determine the mRNA and DNA base sequences that lead to it.

What changes in the DNA sequence are responsible for the change?

What changes would occur in the protein if the following changes were made in the DNA?

Replace the fourth guanine with an adenine. (Substitution)

Remove everything between the fourth and fifth guanine. (Deletion)

Insert ACT in front of the fourth guanine. (Addition)

Insert ACTG in front of the fourth guanine. (Addition)

A variety of answers are possible for the questions above because more than one codon codes for each amino acid. The important thing here is that you have investigated the consequences (in protein) of a variety of DNA mutations. Check with the instructor in the lab or another student if you would like to have your work checked.

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E-mail instructor: Sue Eggling

Clackamas Community College
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