Genes and

Germinal and Somatic Mutations

Spontaneous and Induced Mutations

Types of Mutations

Complementation Testing

Genetic Topics

Spontaneous and Induced Mutations

In general, the appearance of a new mutation is a rare event. Most mutations that were originally studied occurred spontaneously. This class of mutation is termed spontaneous mutations. Historically, geneticists recognized these in nature. The mutations were collected, and the inheritance of these mutations were analyzed. But these mutations clearly represent only a small number of all possible mutations. To genetically dissect a biological system further, new mutations were created by scient ists by treating an organism with a mutagenizing agent. These mutations are called induced mutations.

The spontaneous mutation rate varies. Large gene provide a large target and tend to mutate more frequently. A study of the five coat color loci in mice showed that the rate of mutation ranged from 2 x 10-6 to 40 x 10-6 mutations per gamete per gene. Data from several studies on eukaryotic organisms shows that in general the spontaneous mutation rate is 2-12 x 10-6 mutations per gamete per gene. Given that the human genome contains 100,000 genes, we can conclude that we would predict that 1-5 human gametes would contain a mutation in some gene.

Mutations can be induced by several methods. The three general approaches used to generate mutations are radiation, chemical and transposon insertion. The first induced mutations were created by treating Drosophila with X-rays. Using this a pproach Mueller to induce lethal mutations. In addition to X-rays, other types of radiation treatments that have proven useful include gamma rays and fast neutron bombardment. These treatments can induce point mutations (changes in a single nucleotide) or deletions (loss of a chromosomal segment).

Chemical mutagens work mostly by inducing point mutations. Point mutations occur when a single base pair of a gene is changed. These changes are classified as transitions or transversions. Transitions occur when a purine is convert ed to a purine (A to G or G to A) or a pyrimide is converted to a pyrimidine (T to C or C to T). A transversion results when a purine is converted to a pyrimidine or a pyrimidine is converted to a purine. A transversion example is adenine being converte d to a cytosine. You can determine other examples.

Two major classes of chemical mutagens are routinely used. These are alkylating agents and base analogs. Each has a specific effect on DNA. Alkylating agents [such as ethyl methane sulphonate (EMS), ethyl ethane sulphonate (EES) and musta rd gas] can mutate both replicating and non-replicating DNA. By contrast, a base analog (5-bromouracil and 2-aminopurine) only mutate DNA when the analog is incorporated into replicating DNA. Each class of chemical mutagen has specific effects that can lead to transitions, transversions or deletions.

Scientists are now using the power of transposable elements to create new mutations. Transposable elements are mobile pieces of DNA that can move from one location in a geneome to another. Often when they move to a new location, the result is a new mutan t. The mutant arises because the presence of a piece of DNA in a wild type gene disrupts the normal function of that gene. As more and more is being learned about genes and genomes, it is becoming apparent that transposable elements are a power source f or creating insertional mutants.

The detailed knowledge of the structure and funciton of transposable elements is now being applied in the pursuit of new mutations. Stocks are created in which a specific type of element is present. This stock is then crossed to a genetic stock that doe s not contain the element. Once that element enters the virgin stock, it can begin to move around that genome. By carefully observing the offspring, new mutants can be discovered. This approach to developing mutants is termed insertional mutagenesis.

Copyright © 1999. Phillip McClean