Mutations

Substitution

A substitution is a mutation that exchanges one base for another (i.e., a change in a single "chemical letter" such as switching an A to a G). Such a substitution could:

change a codon to one that encodes a different amino acid and cause a small change in the protein produced. For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced.
change a codon to one that encodes the same amino acid and causes no change in the protein produced. These are called silent mutations.
change an amino-acid-coding codon to a single "stop" codon and cause an incomplete protein. This can have serious effects since the incomplete protein probably won't function.

Why is the changing of a single base the least serious form of mutation?

Addition and deletion mutations generally produce nonfunctional proteins or no protein product at all. They are frameshift mutations. A frameshift mutation alters the ‘reading frame’ of the DNA sequence and changes all the amino acids in the protein product after the point of mutation. Substitution mutations merely replace one base with another. Because the genetic code is redundant some substitutions will have no effect at all. For example the substitution of a uracil for a cytosine in the codon CCU will have no effect on the protein produced as both CCU and CCC code for proline. Substitutions that replace one amino acid with another vary widely in their effect depending on the substitution and its location in the amino acid chain.

A substitution that produces the stop codon (AUG) is the most serious as it will end an amino acid chain prematurely. Other substitutions can have severe effects if the replacement of an amino acid radically changes the shape of the protein or the active site. Changes that have minimal effect on the protein configuration are less likely to dramatically effect the functioning of the protein

Types of Mutations

Insertion

Insertions are mutations in which extra base pairs are inserted into a new place in the DNA.

Deletion

Deletions are mutations in which a section of DNA is lost, or deleted.

Frameshift

Since protein-coding DNA is divided into codons three bases long, insertions and deletions can alter a gene so that its message is no longer correctly parsed. These changes are called frameshifts.

For example, consider the sentence, "The fat cat sat." Each word represents a codon. If we delete the first letter and parse the sentence in the same way, it doesn't make sense.

In frameshifts, a similar error occurs at the DNA level, causing the codons to be parsed incorrectly. This usually generates truncated proteins that are as useless as "hef atc ats at" is uninformative.

There are other types of mutations as well, but this short list should give you an idea of the possibilities.

Missense mutation: This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.

Nonsense mutation: A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.

Insertion An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly.

Deletion :A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).

Duplication : A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.

Frameshift mutation

This type of mutation occurs when the addition or loss of DNA bases changes a gene's reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.

Click to investigate what happens when proteins are mutated.

Changes in Chromosome Structure

The pairing of homologous chromosomes during prophase I of meiosis can lead to a number of errors. This animation describes how miss-pairings can result in duplication or deletion of entire sections of chromosomes or inversions of sections so that the order of a DNA sequence is reversed with respect to the rest of the chromosome. Given the potential problems associated chromosome pairing in meiosis, why are genes organized onto chromosomes. Why is the DNA for each gene not an independent unit? There are two probable answers to this question. One is that regulatory sites are usually located next to the protein coding genes they control. Regulation that is based on location requires that genes be organized onto larger structures. Also, if each gene was an independent unit during meiosis, the cell would have to pair up thousands and thousands of alleles. Even if cells were capable of doing this the rate of error would be extremely high.

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