Factors Influencing The Mutation Rate
Within a single organism, the mutation rate of two genes can differ by a thousandfold or more, so within a species some mutations may be very rare and others quite common. Exposures to very high doses of very potent mutagens can increase the mutation rate per generation by more than a hundredfold.
Both the nature of the gene and its environment can influence the mutation rate. The size of the gene, its base composition, its position in the genome, and whether or not it is being actively transcribed influence its mutation rate. The dystrophin gene, mutated in Duchenne muscular dystrophy, is thought to have a mutation rate of one in every ten thousand births, while the gene, mutated in Huntington's disease, has a mutation rate of closer to one in one million. The explanation for this difference is, at least in part, gene size: The dystrophin gene is one of the largest known. Genes whose promoter regions have been silenced by methylation (the addition of-CH3 units to cytosine bases) are more likely to be mutated, since methylcytosine is easily converted to a base that resembles thymine.
In addition, the repair capacity of the organism can be important in determining how many mutations ultimately remain in the genome. For example, Bloom syndrome, a human cancer-causing condition, causes a decreased ability to repair DNA damage and an elevated mutation rate. Exposure to environmental mutagens or to protective agents, possibly dietary, can alter the mutation rate. Since the mutation rate is partly under genetic control, it is a selected characteristic of an organism, with the burden of detrimental mutations being balanced by the benefit of rare favorable mutations that are adaptive and permit evolution of the species.
One important factor influencing observed mutation rates is the means by which mutations are detected, as some methods may detect a changes at only one or two base pairs of a specific gene, leaving others undetected. Obviously the mutation rate observed by such methods will be lower than if more altered bases could be detected.
Mutations can also change a mutated gene back to the normal, wild-type form of the gene. Such "back" mutations are typically much rarer than "forward" mutations. This is because the number of ways to inactivate a gene is much greater than the number of ways to fix it. Imagine there are 1,000 bases that could be changed to produce a forward mutation. To reverse one of these mutations, it is necessary to change the one specific base pair that has mutated, and to change it back to the base it was before, rather than to a different one. Therefore, a back mutation rate of less than 1 one-thousandth of the forward rate would be expected.
- Mutation Rate - The Origin Of Spontaneous Mutations
- Mutation Rate - Human Mutation Rates
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