Module 7 Molecular Genetics

3.7.4 page 2

Read

The structure of DNA is not permanent. It is actually constantly changing. Enzymes like DNA polymerase repair many changes immediately, but many are missed and not fixed. If a change is permanent it is called a mutation. If a mutation occurs in a body cell (somatic cell mutation), the mutation will be passed on to daughter cells when the cell divides, therefore likely only affecting the individual organism. When a mutation occurs in the DNA of a gamete cell (germ line mutation), this mutation will be passed on to the next generation of organisms. Germ line mutations are one way that genetic variation in a population can occur. Some of the different types of mutations that can occur are described below.

Point mutations occur when one of the following occurs:

• substitution of one nucleotide for another
• insertion of one or more nucleotide
• deletion of one or more nucleotides

Substitution

The effect of a substitution will depend on the actual nucleotide substituted and the subsequent effect on the protein. We will use the example below to see what the effects of a substitution mutation can be. Example A is the normal mRNA nucleotide sequence and coding amino acid sequence.

Example A

UGC  AUA  AAU GGC ← mRNA

cys – iso – asp – gly ← amino acid sequence

Example B

UGC  AUC  AAU GGC
cys – iso – asp – gly

In Example B above, a C nucleotide was substituted for the A nucleotide in the second codon triplet. Both the original triplet AUA and the mutated triplet AUC code for the same amino acid, isoleucine. This type of mutation, where the protein or amino acid chain is not affected, is called a silent mutation.

In Example C below, you can see that the substitution of U for A in the second triplet does cause a change in the amino acid coded for this time. This type of mutation is called a mis-sense mutation and can cause the protein to not work, or to be less effective. This is the type of mutation that causes the harmful sickle cell anemia disease. This type of mutation could also develop new forms of proteins that might meet different needs.

Example C

UGC  UUA  AAU GGC

cys –  leu –  asp –  gly

Example D

UGA  AUA  AAU GGC

Stop*

Some substitutions like the one in example D don’t allow the protein to function at all. In example D, the amino acid sequence is terminated and the protein will be cut short and be non-functioning. This is an example of a non-sense mutation.

Insertion and deletion mutations can cause a frameshift mutation. These mutations cause the entire reading frame of the gene to be altered, and results in a nonsense mutation. Take a look at example E below.

Example E

UGC  AUA  AAU GGC      NORMAL original
cys –  iso –  asp –  gly

UGC  AUGA  AAU GGC    mRNA after insertion of one nucleotide
 

UGC AUG AAA UGG C     frameshift caused by insertion, resulting new amino acid sequence
cys – met – lys - trp

Chromosomal mutations are another type of mutation that you looked at earlier in this module. These mutations occur when chromosomes cross over and recombine genetic material. Other chromosomal mutations can occur if part of the chromosome is lost, or duplicated during DNA replication. Remember that another event can result in major differences. That event is non-disjunction, as you learned in a previous lesson. In non-disjunction, because chromosomes are not segregated correctly, cells can result that have too many (trisomy), or not enough (monosomy) chromosomes.

Read pages 643 and 644 to review these different types of mutations.

Self-Check

Answer the following questions, then compare your answer to the suggested responses. How was your understanding of the different types of mutations? If you had trouble with these questions, contact your instructor and skip ahead to watch the video near the end of this lesson. The video may explain mutations in a different way that could help your understanding.

1. What feature of the genetic code helps to protect a cell from the effects of nucleotide substitution?
2. What is a frameshift mutation?
3. Why is a mutation caused by an insertion or a deletion more likely to have serious consequences for a cell than one caused by a substitution?
4. One mutation results in the replacement of a G nucleotide with a T nucleotide in the sense strand of a DNA molecule. Under what circumstances will this substitution produce each of the following mutations?
   
   
   1. A silent mutation
   2. A mis-sense mutation
   3. A nonsense mutation
5. Explain the difference between a germ line mutation and a somatic cell mutation. Which type of mutation contributes more to the variations among organisms?