Mutation rate
Encyclopedia
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). 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 mutation
s 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. 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 virus
es 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. This is termed error catastrophe
.
) per base pair per generation. For example, mutations in so-called Junk DNA which do not affect organism function tend to accumulate at a faster rate than mutations in DNA that is actively in use in the organism (gene expression
). That is not necessarily due to a higher mutation rate, but to lower levels of purifying selection. A region which mutates at predictable rate is a candidate for use as a molecular clock
.
If the rate of neutral mutations in a sequence is assumed to be constant (clock-like), and if most differences between species are neutral rather than adaptive, then the number of differences between 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
.
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.
In general, the mutation rate in eukaryotes and bacteria
is roughly 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. Human mitochondrial DNA has been estimated to have mutation rates of ~3× or ~2.7×10−5 per base per 20 year generation (depending on the method of estimation); these rates are considered to be significantly higher than rates of human genomic mutation at ~2.5×10−8 per base per generation. Using data available from whole genome sequencing, the human genome mutation rate is similarly estimated to be ~1.1×10−8 per site per generation .
The rate for other forms of mutation also differs wildly from point mutations. An individual microsatellite locus often has a mutation rate on the order of 10−4, though this can differ wildly with length.
s (Alpha) and transversion
s (Beta).
of mutation rate. The optimal mutation rate of organisms may be determined by a trade-off between costs of a high mutation rate, such as deleterious mutations, and the metabolic
costs of maintaining systems to reduce the mutation rate, such as DNA repair enzymes. Additionally, higher mutation rates increase the rate of beneficial mutations, and evolution may prevent a lowering of the mutation rate in order to maintain optimal rates of adaptation. Finally, natural selection may fail to optimize the mutation rate because of the relatively minor benefits of lowering the mutation rate, and thus the observed mutation rate is the product of neutral processes. Viruses that use RNA as their genetic material have rapid mutation rates, which can be an advantage since these viruses will evolve constantly and rapidly, and thus evade the defensive responses of e.g. the human immune system
.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, the mutation rate is the chance of a mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
occurring in an organism or gene in each generation (or, in the case of multicellular organisms, cell division). 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
Oncology
Oncology is a branch of medicine that deals with cancer...
.
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 mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s 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
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
, unfavorable mutations will typically be eliminated from a population while favorable and neutral changes accumulate. 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
Polymerase
A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...
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 virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
es such as poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...
with ribavirin
Ribavirin
Ribavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
produce results consistent with the idea that the viruses mutated too frequently to maintain the integrity of the information in their genomes. This is termed error catastrophe
Error catastrophe
Error catastrophe is a term used to describe the extinction of an organism as a result of excessive RNA mutations. The term specifically refers to the predictions of mathematical models similar to that described below, and not to an observed phenomenon.Like every organism, viruses 'make mistakes'...
.
Species
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 mutationsFixation (population genetics)
In population genetics, fixation is the change in a gene pool from a situation where there exist at least two variants of a particular gene to a situation where only one of the alleles remains...
) per base pair per generation. For example, mutations in so-called Junk DNA which do not affect organism function tend to accumulate at a faster rate than mutations in DNA that is actively in use in the organism (gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
). That is not necessarily due to a higher mutation rate, but to lower levels of purifying selection. A region which mutates at predictable rate is a candidate for use as a molecular clock
Molecular clock
The molecular clock is a technique in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation...
.
If the rate of neutral mutations in a sequence is assumed to be constant (clock-like), and if most differences between species are neutral rather than adaptive, then the number of differences between two different species can be used to estimate how long ago two species diverged (see molecular clock
Molecular clock
The molecular clock is a technique in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation...
). 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
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
.
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.
In general, the mutation rate in eukaryotes and bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
is roughly 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. Human mitochondrial DNA has been estimated to have mutation rates of ~3× or ~2.7×10−5 per base per 20 year generation (depending on the method of estimation); these rates are considered to be significantly higher than rates of human genomic mutation at ~2.5×10−8 per base per generation. Using data available from whole genome sequencing, the human genome mutation rate is similarly estimated to be ~1.1×10−8 per site per generation .
The rate for other forms of mutation also differs wildly from point mutations. An individual microsatellite locus often has a mutation rate on the order of 10−4, though this can differ wildly with length.
Mutational spectrum
There is a systematic difference in rates for transitionTransition (genetics)
In genetics, a transition is a point mutation that changes a purine nucleotide to another purine or a pyrimidine nucleotide to another pyrimidine . Approximately two out of three single nucleotide polymorphisms are transitions....
s (Alpha) and transversion
Transversion
In molecular biology, transversion refers to the substitution of a purine for a pyrimidine or vice versa. It can only be reverted by a spontaneous reversion. Because this type of mutation changes the chemical structure dramatically, the consequences of this change tend to be more drastic than those...
s (Beta).
Evolution
There are three theories on what determines the evolutionEvolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
of mutation rate. The optimal mutation rate of organisms may be determined by a trade-off between costs of a high mutation rate, such as deleterious mutations, and the metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
costs of maintaining systems to reduce the mutation rate, such as DNA repair enzymes. Additionally, higher mutation rates increase the rate of beneficial mutations, and evolution may prevent a lowering of the mutation rate in order to maintain optimal rates of adaptation. Finally, natural selection may fail to optimize the mutation rate because of the relatively minor benefits of lowering the mutation rate, and thus the observed mutation rate is the product of neutral processes. Viruses that use RNA as their genetic material have rapid mutation rates, which can be an advantage since these viruses will evolve constantly and rapidly, and thus evade the defensive responses of e.g. the human immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
.
See also
- Allele frequencyAllele frequencyAllele frequency or Gene frequency is the proportion of all copies of a gene that is made up of a particular gene variant . In other words, it is the number of copies of a particular allele divided by the number of copies of all alleles at the genetic place in a population. It can be expressed for...
- EvolvabilityEvolvabilityEvolvability is defined as the capacity of a system for adaptive evolution. Evolvability is the ability of a population of organisms to not merely generate genetic diversity, but to generate adaptive genetic diversity, and thereby evolve through natural selection.In order for a biological organism...
- Luria–Delbrück experiment
- MutationMutationIn molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...