Mutations

To be able to understand the generation of different alleles we have to introduce the concept of mutations. Mutations are changes in the sequence of the genetic information. In the living cell, the DNA undergoes frequent chemical change, especially when it is being replicated. Most of these changes are fixed or removed by the cell's DNA-repair mechanisms. Even though the cellular machinery works very precisely there are still some changes that are not corrected and result in a mutation (about 1 in every 200 million base pairs). Mutations can also be introduced by exposure to environmental factors called mutagens, such as certain chemicals, α,β and γ-radiation, X-rays and UV-light. Although mutations can be dangerous for an individual, especially if caused by heavy exposure to mutagens, we have to remember that mutations are an necessary part of the system and as we shall see the raw material for evolution.

Mutations in the DNA sequence of a gene can be compared to typos in a sentence of a text. There are many different ways to alter a gene, just as there are many different ways to introduce typos into a sentence. The effects of changes in a sentence are more obvious than in a real genetic sequence like e.g. "GAT TAC AGG CAT TTA AAA AGC" which only contains four letters (bases A,T,C and G). Therefore we are going to illustrate the effects of mutation using the sentence "THE FAT CAT ATE THE HOT DOG". This imaginary gene has only three-letter words, in the same way that three bases code for one amino acid in gentic code. In this example the meaning of the sentence corresponds to the function of our imaginary gene.

We are going to mutate the sentence in by just replacing or adding one letter. Such mutations are called point mutations.
    • Allele 0: THE FAT CAT ATE THE HOT DOG
    • Allele 1: THE FAT RAT ATE THE HOT DOG
    • Allele 0: THE FAT CAT ATE THE HOT DOG
    • Allele 2: THE FAT CAR ATE THE HOT DOG
    • Allele 0: THE FAT CAT ATE THE HOT DOG
    • Allele 3: THE FAT KAT ATE THE HOT DOG
    • Allele 0: THE FAT CAT ATE THE HOT DOG
    • Allele 4: THE FAT CAM TAT ETH EHO TDO G
Exercise: Classify the Mutations in the Sentance.
Q. Can you identify the different mutations in all four examples? In what way did they change the meaning of the sentence?
A.
  1. In the first example a C was replaced by an R changing the meaning of the word from CAT to RAT. The meaning of the sentence is changed but it still makes sense, cats and rats have been known to eat hot dogs. This is comparable to a mutation that changes an amino acid to one biochemically similar to the original. For example in the genetic code CAT codes for the amino acid Histidine while GAT leads to Aspartic Acid.
  2. The T of CAT was replaced by an R in the second mutation changing the meaning of the word from CAT to CAR. Unlike the mutation in 1 this has a more pronounced effect on the meaning of the sentance, cars don't eat hot dogs. This corresponds to a mutation that changes the amino acid to a biochemically different one , which can alter the function of the protein.
  3. In the third example the C of CAT was replaced by a K. The words KAT and CAT sound exactly the same and have no real effect on the meaning to the sentance. In a gene this happens when both 3-letter-codes stand for the same Amino Acid, e.g. CAT and CAA code for the amino acid Histidine and is known as a silent mutation.
  4. The fourth mutation was an insertion of the letter G between the A and the T of the word CAT. Not only the word (3 letter code) in which the mutation occurred is changed but also all following words.
Q. Which of the four has the strongest effect on the sentence?
A. The last mutation (4) also introduces one letter (base) but it changes all following words. That means most amino acids in the protein will be changed. In most cases the protein completely loses its function.
Q. What other mutations do you know or can you think of?
A. There are two other groups of mutations. The first one is chromosome mutations and the second one genome mutations. Following the example of genes as sentences, the chromosome would be chapters of book and the genome the whole book. From this genetic book as examples for chromosome mutations you can cut out a part of page and paste somewhere else in the chapter (gene translocation), or you can copy a sentence several times in a row which would be a gene dublications. But you could also rip out a whole chapter (chromosome) as well as you could add chapter. The latter two are exapmles of genoms mutations.

You can see here how easily four different variants (alleles) of the sentence (gene) with new meanings (functions) were created. A mutation like this happens 8 times (once every 200 million base pairs) during the replication of human DNA, but often times in silent areas where there are no genes. Now we want to look at the fate of a freshly mutated allele.