8. DNA and RNA. The Molecular Basis of Heredity


8.6. Mutations and Protein Synthesis


A mutation is any change in the DNA sequence of an organism. They can occur for many reasons, including errors during DNA replication. Mutations can also be caused by external factors, such as radiation, carcinogens, drugs, or even some viruses. It is important to understand that not all mutations cause a change in an organism. If a mutation occurs away from the protein-coding sequence and the DNA sequences that regulate its expression, it is unlikely that the change will be harmful to the organism. On occasion, the changes that occur because of mutations can be helpful and will provide an advantage to the offspring that inherit that change.

Scientists are not yet able to consistently predict the effects that a mutation will have on the entire organism. Changes in a protein’s amino acid sequence may increase or decrease the protein’s level of activity. The mutations may also completely stop the protein’s function. Less frequently, a change in the amino acid sequence may create a wholly novel function. In any case, to predict the effect that a mutation will have would require knowing how the proteins work in a variety of different cells, tissues, organs, and organ systems. With our current understanding, this is not always possible. Our best method of understanding a mutation is to observe its effects directly in an organism that carries the mutation.


Point Mutations

A point mutation is a change in a single nucleotide of the DNA sequence. Point mutations can potentially have a variety of effects even though they change only one nucleotide. Three different kinds of point mutations are recognized, (a) missense, (b) silent, and (c) nonsense.


Missense Mutation

A missense mutation is a point mutation that causes the wrong amino acid to be used in making a protein. A sequence change that resulted in the codon change from UUU to GUU would use valine instead of phenylalanine. The shapes and chemical properties of enzymes are determined by the correct sequence of various types of amino acids. Substituting one amino acid for another can create an abnormally functioning protein.

The condition known as sickle-cell anemia provides a good example of the effect caused by a simple missense mutation. Hemoglobin is a protein in red blood cells that is responsible for carrying oxygen to the body’s cells. Normal hemoglobin molecules are composed of four separate, different proteins. The proteins are arranged with respect to each other so that they are able to hold an iron atom. The iron atom is the portion of hemoglobin that binds the oxygen.

In normal individuals, the amino acid sequence of the hemoglobin protein begins like this:

In some individuals, a single nucleotide of the hemoglobin gene has been changed. The result of this change is a hemoglobin protein with an amino acid sequence of:

Glutamic acid (Glu) is coded by two codons: GAA and GAG. Valine is also coded by two codons: GUA and GUG. The change that causes the switch from glutamic acid to valine is a missense mutation. With this small change, the parts of the hemoglobin protein do not assemble correctly under low oxygen levels.

When the oxygen levels in the blood are low, many hemoglobin molecules stick together and cause the red blood cells to have a sickle shape, rather than their normal round, donut shape (figure 8.13). The results can be devastating:

• The red blood cells do not flow smoothly through the capillaries, causing the red blood cells to tear and be destroyed. This results in anemia.

• Their irregular shapes cause them to clump, clogging the blood vessels. This prevents oxygen from reaching the oxygen-demanding tissues. As a result, tissues are damaged.

• A number of physical disabilities may result, including weakness, brain damage, pain and stiffness of the joints, kidney damage, rheumatism, and, in severe cases, death.



FIGURE 8.13. Normal and Sickled Red Blood Cells

(a) A normal red blood cell and (b) a cell having the sickle shape. This sickling is the result of a single amino acid change in the hemoglobin molecule.


Silent Mutation

A silent mutation is a nucleotide change that results in either the placement of the same amino acid or a different amino acid but does not cause a change in the function of the completed protein. An example of a silent mutation is the change from UUU to UUC in the mRNA. The mutation from U to C does not change the amino acid present in the protein. It still results in the amino acid phenylalanine being used to construct the protein. Another example is shown in figure 8.14.



FIGURE 8.14. Kinds of Point Mutations

A nucleotide substitution changes the protein only if the changed codon results in a different amino acid being substituted into a protein chain. (a) In the example, the original codon, CAA, calls for the amino acid glutamine. (b) A silent mutation is shown where the third position of the codon is changed. The codon CAG calls for the same amino acid as the original version (CAA). Because the proteins produced in example (a) and example (b) will be identical in amino acid sequence, they will function the same also. (c) A nonsense mutation is shown where the codon UAA stops the synthesis of the protein. (d) A missense mutation occurs when the nucleotide in the second position of the codon is changed. It now reads AAA. The codon AAA calls for the amino acid lysine. This mutation may alter protein function.


Nonsense Mutation

Another type of point mutation, a nonsense mutation, causes a ribosome to stop protein synthesis by introducing a stop codon too early. For example, a nonsense mutation would be caused if a codon were changed from CAA (glutamine) to UAA (stop). This type of mutation results in a protein that is too short. It prevents a functional protein from being made because it is terminated too soon. Human genetic diseases that result from nonsense mutations include (a) cystic fibrosis (caused by certain mutations in the cystic fibrosis transmembrane conductance regulator gene), (b) Duchenne muscular dystrophy (caused by mutations in the dystrophin gene), and (c) beta thalassaemia (caused by mutations in the P-globin gene).


Insertions and Deletions

Several other kinds of mutations involve larger spans of DNA than a change in a single nucleotide. Insertions and deletions are different from point mutations because they change the DNA sequence by adding and removing nucleotides. An insertion mutation adds one or more nucleotides to the normal DNA sequence. This type of mutation can potentially add amino acids to the protein and change its function. A deletion mutation removes one or more nucleotides and can potentially remove amino acids from the protein and change its function.


Frameshift Mutations

Insertions and deletions can also affect amino acids that are coded after the mutation by causing a frameshift. Ribosomes read the mRNA three nucleotides at a time. This set of three nucleotides is called a reading frame. A frameshift mutation occurs when insertions or deletions cause the ribosome to read the wrong sets of three nucleotides. Consider the example shown in figure 8.15. Frameshift mutations can result in severe genetic diseases such as Tay-Sachs and some types of familial hypercholesterolemia. Tay-Sachs disease (caused by mutations in the beta-hexosaminidase gene) affects the breakdown of lipids in lysosomes. It results in damage to the nervous system, including blindness, paralysis, psychosis, and early death of children.



FIGURE 8.15. Frameshift

A frameshift causes the ribosome to read the wrong set of three nucleotides on the mRNA. Proteins produced by this type of mutation usually bear little resemblance to the normal protein that is usually produced. In this example, the normal sequence is shown for comparison with the mutated sequence. The mutated sequence is missing two uracil nucleotides. The underlining identifies sets of nucleotides that are read by the ribosome as a codon. A normal protein is made until after the deletion is encountered.


Mutations Caused by Viruses

Some viruses can insert their genetic code into the DNA of their host organism. When this happens, the presence of the new viral sequence may interfere with the cells’ ability to use genetic information in that immediate area of the insertion. In such cases, the virus’s genetic information becomes an insertion mutation. In the case of some retroviruses, such as the human papillomavirus (HPV), the insertion mutations increase the likelihood of cancer of the penis, anus, and cervical cancer. These cancers are caused when mutations occur in genes that help regulate when a cell divides (figure 8.16).





Genital warts and some genital cancers (particularly cervical cancer) are caused by the human papillomavirus (HPV). Over 70 papillomaviruses are shown in this photo, taken through an electron microscope. Several HPV strains have been associated with a higher than normal incidence of cancer. This is because HPV creates insertion mutations in the cells it infects.


Chromosomal Aberrations

A chromosomal aberration is a major change in DNA that can be observed at the level of the chromosome. Chromosomal aberrations involve many genes and tend to affect many different parts of the organism if it lives through development. There are four types of aberrations: inversions, translocations, duplications, and deletions. An inversion occurs when a chromosome is broken and a piece becomes reattached to its original chromosome, but in a flipped orientation. A translocation occurs when one broken segment of DNA becomes integrated into a different chromosome. Duplications occur when a portion of a chromosome is replicated and attached to the original section in sequence. Deletion aberrations result when a broken piece becomes lost or is destroyed before it can be reattached. All of these aberrations are considered mutations. Because of the large segments of DNA that are involved with these types of mutations, many genes can be affected.

In humans, chromosomal aberrations frequently prevent fetal development. In some cases, however, the pregnancy can be carried full term. In these situations, the effects of the mutations vary greatly. In some cases, there are no noticeable differences. In other cases, the effects are severe. Cri-du-chat (cry of the cat) is a disorder that is caused by a deletion of part of chromosome number 5. It occurs with between 1 in 25,000 to 50,000 births. The key symptom is a high-pitched, cat-like cry of the infants. This is thought to be due to a variety of things that include poor muscle tone. Facial characteristics such as a small head, widely set eyes, and low-set ears are also typical. Mild to severe mental disabilities are also symptoms. There appears to be a correlation between the deletion size and the symptoms; larger regions of deleted DNA tends to correlate to more severe symptoms.

Many other forms of mutations affect DNA. Some damage to DNA is so extensive that the entire strand is broken, resulting in the synthesis of abnormal proteins or a total lack of protein synthesis. A number of experiments indicate that many street drugs, such as lysergic acid diethylamide (LSD), are mutagenic agents that cause DNA to break.


Mutations and Inheritance

Mutations can be harmful to the individual who first gains the mutation, but changes in the structure of DNA may also have harmful effects on the next generation if they occur in the sex cells. Sex cells transmit genetic information from one generation to the next. Mutations that occur to DNA molecules can be passed on to the next generation only when the mutation is present in cells such as sperm and egg. In the next several chapters, we will look at how DNA is inherited. As you read the next chapters remember that DNA codes for proteins. Genetic differences between individuals are the result of slightly different enzymes.



16. Both chromosomal and point mutations occur in DNA. In what ways do they differ?

17. What is a silent mutation? Provide an example.



The successful operation of a living cell depends on its ability to accurately use the genetic information found in its DNA. DNA replication results in an exact doubling of the genetic material. The process virtually guarantees that identical strands of DNA will be passed on to the next generation of cells. The production of protein molecules is under the control of the nucleic acids, the primary control molecules of the cell. The sequence of the bases in the nucleic acids, DNA and RNA, determines the sequence of amino acids in the protein, which in turn determine the protein’s function. Protein synthesis involves the decoding of the DNA into specific protein molecules and the use of the intermediate molecules, mRNA and tRNA, at the ribosome. The process of protein synthesis is controlled by regulatory sequences in the nucleic acids. Errors in any of the protein coding sequences in DNA may produce observable changes in the cell’s functioning and can lead to cell death.


Basic Review

1. Genetic information is stored in what type of chemical?

a. proteins

b. lipids

c. nucleic acids

d. sugars

2. The difference between ribose and deoxyribose is

a. the number of carbon atoms.

b. an oxygen atom.

c. one is a sugar and one is not.

d. No difference—they are the same molecule.

3. The nitrogenous bases in DNA

a. hold the two DNA strands together.

b. link the nucleotides together.

c. are part of the genetic blueprint.

d. Both a and c are correct.

4. Transcription copies genetic information

a. from DNA to RNA.

b. from proteins to DNA.

c. from DNA to proteins.

d. from RNA to proteins.

5. RNA polymerase starts synthesizing mRNA in eukaryotic cells because

a. it finds a promoter sequence.

b. transcription factors interact with RNA polymerase.

c. the gene is in a region of loosely packed chromatin.

d. All of the above are true.

6. Under normal conditions, translation

a. forms RNA.

b. reads in sets of three nucleotides called codons.

c. occurs in the nucleus.

d. All of the above statements are true.

7. The function of tRNA is to

a. be part of the ribosome’s subunits.

b. carry the genetic blueprint.

c. carry an amino acid to a working ribosome.

d. Both a and c are correct.

8. Enhancers

a. make ribosomes more efficient at translation.

b. prevent mutations from occurring.

c. increase the transcription of specific genes.

d. slow aging.

9. The process that removes introns and joins exons from mRNA is called

a. silencing.

b. splicing.

c. transcription.

d. translation.

10. A deletion of a single base in the protein-coding sequence of a gene will likely create

a. no problems.

b. a faulty RNA polymerase.

c. a tRNA.

d. a frameshift.

11. Which is an example of a missense mutation?

a. Tay-Sachs disease

b. sickle-cell anemia


d. virulent disease

12. Which best describes the sequence of events followed by the human immunodeficiency virus in its replication?

a. DNA  RNA  protein

b. RNA  RNA  protein


d. DNA  RNA  protein


13. If the two subunits of a ribosome do not come together with an mRNA molecule, which will not occur?

a. transcription

b. translation

c. replication

d. All the above are correct.

14. Which of the following pairs would be incorrect according to the base-pairing rule?

a. in DNA: AT

b. in DNA: GC

c. in RNA: UT

d. in RNA: GC

15. Using the amino acid-nucleic acid dictionary, which amino acid would be coded for by the mRNA codon GAC?

a. asparagine

b. aspartic acid

c. isoleucine

d. valine



1. c 2. b 3. d 4. a 5. d 6. b 7. c 8. c 9. b 10. d 11. b 12. c 13. b 14. c 15. B


Thinking Critically

Gardening in Depth

A friend of yours gardens for a hobby. She has noticed that she has a plant that no longer produces the same color of flower it did a few years ago. It used to produce red flowers; now, the flowers are white. Consider that petal color in plants is due to at least one enzyme that produces the color pigment. No color suggests no enzyme activity. Using what you know about genes, protein synthesis, and mutations, hypothesize what may have happened to cause the change in flower color. Identify several possibilities; then, identify what you would need to know to test your hypothesis.