Mutation rate

In genetics, the mutation rate is the chance of a mutation occurring in an organism or gene in each generation (or, in the case of multicellular organisms, cell division). See Luria-Delbrück experiment. The mutation frequency is the number of individuals in a population with a particular mutation, and tends to be reported more often as it is easier to measure (for instance, there is no need to restrict the population to experiencing only one generation, as needed to measure mutation rate). This is important in fields such as evolutionary biology and oncology.

In evolutionary biology, mutations can have a neutral, favorable or unfavorable effect on the organism, with respect to the present environment. The effect of a low mutation rate on a population is that few variations are available to respond to sudden environmental change. This means the species is slower to adapt. A higher mutation rate damages more individuals, but by increasing variation in the population could increase the speed at which the population can adapt to changing circumstances. The majority of mutations in a multi-cellular organism's genome are neutral and do not harm the organism. Occasional mutations are unfavorable, and rarely a mutation will be favorable. As a result of natural selection, unfavorable mutations will typically be eliminated from a population while favorable and neutral changes accumulate (genetic drift). The rate of elimination or accumulation depends on how unfavorable or favorable the mutation is.

There appear to be limits on how advantageous a high mutation rate can be, and there is evidence that mutation rates (as determined by polymerase fidelity) are under selection to be neither too high, nor too low. An exciting extension of the idea that mutation rates can be too high is that drugs can be used to increase the mutation rates of pathogens to intolerable levels. Studies have shown that treating RNA viruses such as poliovirus with ribavirin produce results consistent with the idea that the viruses mutated too frequently to maintain the integrity of the information in their genomes.

Mutation rates differ between species and even between different regions of the genome of a single species. This should not be confused with the idea that mutations accumulate at different rates over longer periods of time than a generation. These different rates of nucleotide substitution are measured in substitutions (fixed mutations) per base pair per year. For example, mutations in so-called Junk DNA which do not affect organism function tend to accumulate mutations at a faster rate than DNA which is actively in use by in the organism (gene expression), and this is due not necessarily to higher mutation rate, but lower levels of purifying selection. A region which mutates at predictable rate is a candidate for use as a molecular clock.

If the mutation rate of a gene is assumed to be constant (clock-like) the degree of difference between the same gene in two different species can be used to estimate how long ago two species diverged (see molecular clock). In fact, the mutation rate of an organism may change in response to environmental stress. For example UV light damages DNA, which may result in error prone attempts by the cell to perform DNA repair. An extreme example of this is the increased mutation rate of organisms living near Chernobyl since the nuclear accident.

The human mutation rate is higher in the male germ line (sperm) than the female (egg cells), but estimates of the exact rate have varied by an order of magnitude or more. .

More generally, the mutation rate in eukaryotes is in generally 10-4 to 10-6 mutations per base pair per generation, and for bacteria the rate is around 10-8 per base pair per generation. The highest mutation rates are found in viruses, which can have either RNA or DNA genomes. DNA viruses have mutation rates between 10-6 to 10-8 mutations per base per generation, and RNA viruses have mutation rates between 10-3 to 10-5 per base per generation.