Mutation
Mutation
Mutation
Mutations result from errors during DNA replication, mitosis, and meiosis, or
other types of damage to DNA (such as pyrimidine dimers that may be caused
by exposure to radiation or carcinogens), which then may undergo error-prone
repair (especially microhomology-mediated end joining[2]), or cause an error
during other forms of repair,[3][4] or else may cause an error during replication
(translesion synthesis). Mutations may also result from insertion or deletion of A tulip flower exhibiting a partially
segments of DNA due to mobile genetic elements.[5][6][7] Mutations may or may yellow petal because of a mutation in
not produce discernible changes in the observable characteristics (phenotype) of its genes.
an organism. Mutations play a part in both normal and abnormal biological
processes including: evolution, cancer, and the development of the immune
system, including junctional diversity.
The genomes of RNA viruses are based on RNA rather than DNA. The RNA viral genome can be double-stranded (as in DNA)
or single-stranded. In some of these viruses (such as the single-stranded human immunodeficiency virus) replication occurs
quickly and there are no mechanisms to check the genome for accuracy. This error-prone process often results in mutations.
Mutation can result in many different types of change in sequences. Mutations in genes can either have no effect, alter the product
of a gene, or prevent the gene from functioning properly or completely. Mutations can also occur in nongenic regions. One study
on genetic variations between different species of Drosophila suggests that, if a mutation changes a protein produced by a gene,
the result is likely to be harmful, with an estimated 70 percent of amino acid polymorphisms that have damaging effects, and the
remainder being either neutral or marginally beneficial.[8] Due to the damaging effects that mutations can have on genes,
organisms have mechanisms such as DNA repair to prevent or correct mutations by reverting the mutated sequence back to its
original state.[5]
Contents
Description
History
Causes
Spontaneous mutation
Error-prone replication bypass
Errors introduced during DNA repair
Induced mutation
Classification of types
By effect on structure
Small-scale mutations
Large-scale mutations
By effect on function
By effect on fitness
Distribution of fitness effects
By impact on protein sequence
By inheritance
Special classes
Nomenclature
Mutation rates
Harmful mutations
Beneficial mutations
Prion mutations
Somatic mutation
Amorphic mutations
Hypomorphic and hypermorphic mutations
See also
References
External links
Description
Mutations can involve the duplication of large sections of DNA, usually through genetic recombination.[9] These duplications are
a major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every
million years.[10] Most genes belong to larger gene families of shared ancestry, detectable by their sequence homology.[11] Novel
genes are produced by several methods, commonly through the duplication and mutation of an ancestral gene, or by recombining
parts of different genes to form new combinations with new functions.[12][13]
Here, protein domains act as modules, each with a particular and independent function, that can be mixed together to produce
genes encoding new proteins with novel properties.[14] For example, the human eye uses four genes to make structures that sense
light: three for cone cell or color vision and one for rod cell or night vision; all four arose from a single ancestral gene.[15]
Another advantage of duplicating a gene (or even an entire genome) is that this increases engineering redundancy; this allows one
gene in the pair to acquire a new function while the other copy performs the original function.[16][17] Other types of mutation
occasionally create new genes from previously noncoding DNA.[18][19]
Changes in chromosome number may involve even larger mutations, where segments of the DNA within chromosomes break and
then rearrange. For example, in the Homininae, two chromosomes fused to produce human chromosome 2; this fusion did not
occur in the lineage of the other apes, and they retain these separate chromosomes.[20] In evolution, the most important role of
such chromosomal rearrangements may be to accelerate the divergence of a population into new species by making populations
less likely to interbreed, thereby preserving genetic differences between these populations.[21]
Sequences of DNA that can move about the genome, such as transposons, make up a major fraction of the genetic material of
plants and animals, and may have been important in the evolution of genomes.[22] For example, more than a million copies of the
Alu sequence are present in the human genome, and these sequences have now been recruited to perform functions such as
regulating gene expression.[23] Another effect of these mobile DNA sequences is that when they move within a genome, they can
mutate or delete existing genes and thereby produce genetic diversity.[6]
Nonlethal mutations accumulate within the gene pool and increase the amount of genetic variation.[24] The abundance of some
genetic changes within the gene pool can be reduced by natural selection, while other "more favorable" mutations may
accumulate and result in adaptive changes.
For example, a butterfly may produce offspring with new mutations. The majority of these mutations will have no effect; but one
might change the color of one of the butterfly's offspring, making it harder (or easier) for predators to see. If this color change is
advantageous, the chances of this butterfly's surviving and producing its own offspring are a little better, and over time the
number of butterflies with this mutation may form a larger percentage of the
population.
Neutral mutations are defined as mutations whose effects do not influence the fitness
of an individual. These can increase in frequency over time due to genetic drift. It is
believed that the overwhelming majority of mutations have no significant effect on
an organism's fitness.[25][26] Also, DNA repair mechanisms are able to mend most
changes before they become permanent mutations, and many organisms have
mechanisms for eliminating otherwise-permanently mutated somatic cells.
Prodryas persephone, a Late
Eocene butterfly
Beneficial mutations can improve reproductive success.[27][28]
History
Mutationism is one of several alternatives to evolution by natural selection that
have existed both before and after the publication of Charles Darwin's 1859
book, On the Origin of Species. In the theory, mutation was the source of
novelty, creating new forms and new species, potentially instantaneously,[29] in a
sudden jump.[30] This was envisaged as driving evolution, which was limited by
the supply of mutations.
Understanding of mutationism is clouded by the mid-20th century portrayal of the early mutationists by supporters of the modern
synthesis as opponents of Darwinian evolution and rivals of the biometrics school who argued that selection operated on
continuous variation. In this portrayal, mutationism was defeated by a synthesis of genetics and natural selection that supposedly
started later, around 1918, with work by the mathematician Ronald Fisher.[36][37][38][39] However, the alignment of Mendelian
genetics and natural selection began as early as 1902 with a paper by Udny Yule,[40] and built up with theoretical and
experimental work in Europe and America. Despite the controversy, the early mutationists had by 1918 already accepted natural
selection and explained continuous variation as the result of multiple genes acting on the same characteristic, such as
height.[37][38]
Mutationism, along with other alternatives to Darwinism like Lamarckism and orthogenesis, was discarded by most biologists as
they came to see that Mendelian genetics and natural selection could readily work together; mutation took its place as a source of
the genetic variation essential for natural selection to work on. However, mutationism did not entirely vanish. In 1940, Richard
Goldschmidt again argued for single-step speciation by macromutation, describing the organisms thus produced as "hopeful
monsters", earning widespread ridicule.[41][42] In 1987, Masatoshi Nei argued controversially that evolution was often mutation-
limited.[43] Modern biologists such as Douglas J. Futuyma conclude that essentially all claims of evolution driven by large
mutations can be explained by Darwinian evolution.[44]
Causes
Four classes of mutations are (1) spontaneous mutations (molecular decay), (2) mutations due to error-prone replication bypass of
naturally occurring DNA damage (also called error-prone translesion synthesis), (3) errors introduced during DNA repair, and (4)
induced mutations caused by mutagens. Scientists may also deliberately introduce mutant sequences through DNA manipulation
for the sake of scientific experimentation.
One 2017 study claimed that 66% of cancer-causing mutations are random, 29% are due to the environment (the studied
population spanned 69 countries), and 5% are inherited.[45]
Humans on average pass 60 new mutations to their children but fathers pass more mutations depending on their age with every
year adding two new mutations to a child.[46]
Spontaneous mutation
Spontaneous mutations occur with non-zero probability even given a healthy, uncontaminated cell. They can be characterized by
the specific change:[47]
Tautomerism — A base is changed by the repositioning of a hydrogen atom, altering the hydrogen bonding
pattern of that base, resulting in incorrect base pairing during replication.
Depurination — Loss of a purine base (A or G) to form an apurinic site (AP site).
Deamination — Hydrolysis changes a normal base to an atypical base containing a keto group in place of the
original amine group. Examples include C → U and A → HX (hypoxanthine), which can be corrected by DNA
repair mechanisms; and 5MeC (5-methylcytosine) → T, which is less likely to be detected as a mutation because
thymine is a normal DNA base.
Slipped strand mispairing — Denaturation of the new strand from the template during replication, followed by
renaturation in a different spot ("slipping"). This can lead to insertions or deletions.
Replication slippage
Induced mutation
Induced mutations are alterations in the gene after it has come in contact with mutagens and environmental causes.
Chemicals
Hydroxylamine
Base analogs (e.g., Bromodeoxyuridine (BrdU))
Alkylating agents (e.g., N-ethyl-N-nitrosourea (ENU). These
agents can mutate both replicating and non-replicating
DNA. In contrast, a base analog can mutate the DNA only
when the analog is incorporated in replicating the DNA.
Each of these classes of chemical mutagens has certain
effects that then lead to transitions, transversions, or
deletions.
Agents that form DNA adducts (e.g., ochratoxin A)[53]
DNA intercalating agents (e.g., ethidium bromide)
DNA crosslinkers
Oxidative damage
Nitrous acid converts amine groups on A and C to diazo
groups, altering their hydrogen bonding patterns, which
leads to incorrect base pairing during replication.
Radiation
Classification of types
By effect on structure
The sequence of a gene can be altered in a number of ways.[59] Gene mutations have varying effects on health depending on
where they occur and whether they alter the function of essential proteins. Mutations in the structure of genes can be classified
into several types.
Small-scale mutations
Small-scale mutations affect a gene in one or a few nucleotides. (If only a single nucleotide is affected, they are called point
mutations.) Small-scale mutations include:
Insertions add one or more extra nucleotides into the
DNA. They are usually caused by transposable
elements, or errors during replication of repeating
elements. Insertions in the coding region of a gene
may alter splicing of the mRNA (splice site mutation),
or cause a shift in the reading frame (frameshift), both
of which can significantly alter the gene product.
Insertions can be reversed by excision of the
transposable element.
Deletionsor/Deficiency remove one or more
nucleotides from the DNA. Like insertions, these
mutations can alter the reading frame of the gene. In
general, they are irreversible: Though exactly the
same sequence might, in theory, be restored by an
insertion, transposable elements able to revert a very
short deletion (say 1–2 bases) in any location either
are highly unlikely to exist or do not exist at all.
Substitution mutations, often caused by chemicals or
malfunction of DNA replication, exchange a single
nucleotide for another.[60] These changes are
classified as transitions or transversions.[61] Most
common is the transition that exchanges a purine for a
purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔
T). A transition can be caused by nitrous acid, base
mispairing, or mutagenic base analogs such as BrdU.
Less common is a transversion, which exchanges a
purine for a pyrimidine or a pyrimidine for a purine (C/T
↔ A/G). An example of a transversion is the
conversion of adenine (A) into a cytosine (C). Point
mutations are modifications of single base pairs of
DNA or other small base pairs within a gene. A point
mutation can be reversed by another point mutation, in
which the nucleotide is changed back to its original
state (true reversion) or by second-site reversion (a
complementary mutation elsewhere that results in
regained gene functionality). As discussed below,
point mutations that occur within the protein coding
region of a gene may be classified as synonymous or
nonsynonymous substitutions, the latter of which in
turn can be divided into missense or nonsense
mutations. Five types of chromosomal mutations.
Large-scale mutations
Large-scale mutations in chromosomal structure include:
By effect on function
Loss-of-function mutations, also called inactivating mutations, result in the gene product having less or no
function (being partially or wholly inactivated). When the allele has a complete loss of function (null allele), it is
often called an amorph or amorphic mutation in the Muller's morphs schema. Phenotypes associated with such
mutations are most often recessive. Exceptions are when the organism is haploid, or when the reduced dosage
of a normal gene product is not enough for a normal phenotype (this is called haploinsufficiency).
Gain-of-function mutations, also called activating mutations, change the gene product such that its effect gets
stronger (enhanced activation) or even is superseded by a different and abnormal function. When the new allele
is created, a heterozygote containing the newly created allele as well as the original will express the new allele;
genetically this defines the mutations as dominant phenotypes. Several of Muller's morphs correspond to gain of
function, including hypermorph and neomorph. In December 2017, the U.S. government lifted a temporary ban
implemented in 2014 that banned federal funding for any new "gain-of-function" experiments that enhance
pathogens "such as Avian influenza, SARS and the Middle East Respiratory Syndrome or MERS viruses."[62]
Dominant negative mutations (also called antimorphic mutations) have an altered gene product that acts
antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often
inactive) and are characterized by a dominant or semi-dominant phenotype. In humans, dominant negative
mutations have been implicated in cancer (e.g., mutations in genes p53,[63] ATM,[64] CEBPA[65] and
PPARgamma[66]). Marfan syndrome is caused by mutations in the FBN1 gene, located on chromosome 15,
which encodes fibrillin-1, a glycoprotein component of the extracellular matrix.[67] Marfan syndrome is also an
example of dominant negative mutation and haploinsufficiency.[68][69]
Hypomorphs, after Mullerian classification, are characterized by altered gene products that acts with decreased
gene expression compared to the wild type allele.
Neomorphs are characterized by the control of new protein product synthesis.
Lethal mutations are mutations that lead to the death of the organisms that carry the mutations.
A back mutation or reversion is a point mutation that restores the original sequence and hence the original
phenotype.[70]
By effect on fitness
In applied genetics, it is usual to speak of mutations as either harmful or beneficial.
Mutagenesis experiment: The direct method to investigate the DFE is to induce mutations and then measure the
mutational fitness effects, which has already been done in viruses, bacteria, yeast, and Drosophila. For example,
most studies of the DFE in viruses used site-directed mutagenesis to create point mutations and measure
relative fitness of each mutant.[77][78][79][80] In Escherichia coli, one study used transposon mutagenesis to
directly measure the fitness of a random insertion of a derivative of Tn10.[81] In yeast, a combined mutagenesis
and deep sequencing approach has been developed to generate high-quality systematic mutant libraries and
measure fitness in high throughput.[82] However, given that many mutations have effects too small to be
detected[83] and that mutagenesis experiments can detect only mutations of moderately large effect; DNA
sequence data analysis can provide valuable information about these mutations.
Though relatively few mutations are advantageous, those that are play an important role in evolutionary changes.[90] Like neutral
mutations, weakly selected advantageous mutations can be lost due to random genetic drift, but strongly selected advantageous
mutations are more likely to be fixed. Knowing the DFE of advantageous mutations may lead to increased ability to predict the
evolutionary dynamics. Theoretical work on the DFE for advantageous mutations has been done by John H. Gillespie[91] and H.
Allen Orr.[92] They proposed that the distribution for advantageous mutations should be exponential under a wide range of
conditions, which, in general, has been supported by experimental studies, at least for strongly selected advantageous
mutations.[93][94][95]
In general, it is accepted that the majority of mutations are neutral or deleterious, with advantageous mutations being rare;
however, the proportion of types of mutations varies between species. This indicates two important points: first, the proportion of
effectively neutral mutations is likely to vary between species, resulting from dependence on effective population size; second,
the average effect of deleterious mutations varies dramatically between species.[24] In addition, the DFE also differs between
coding regions and noncoding regions, with the DFE of noncoding DNA containing more weakly selected mutations.[24]
A synonymous substitution replaces a codon with another codon that codes for the same amino acid, so that
the produced amino acid sequence is not modified. Synonymous mutations occur due to the degenerate
nature of the genetic code. If this mutation does not result in any phenotypic effects, then it is called silent, but
not all synonymous substitutions are silent. (There can also be silent mutations in nucleotides outside of the
coding regions, such as the introns, because the exact nucleotide sequence is not as crucial as it is in the
coding regions, but these are not considered synonymous substitutions.)
A nonsynonymous substitution replaces a codon with another codon that codes for a different amino acid, so
that the produced amino acid sequence is modified. Nonsynonymous substitutions can be classified as
nonsense or missense mutations:
A missense mutation changes a nucleotide to cause substitution of a different amino acid. This in turn can
render the resulting protein nonfunctional. Such mutations are responsible for diseases such as
Epidermolysis bullosa, sickle-cell disease, and SOD1-mediated ALS.[97] On the other hand, if a missense
mutation occurs in an amino acid codon that results in the use of a different, but chemically similar, amino
acid, then sometimes little or no change is rendered in the protein. For example, a change from AAA to
AGA will encode arginine, a chemically similar molecule to the intended lysine. In this latter case the
mutation will have little or no effect on phenotype and therefore be neutral.
A nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or
a nonsense codon in the transcribed mRNA, and possibly a truncated, and often nonfunctional protein
product. This sort of mutation has been linked to different mutations, such as congenital adrenal
hyperplasia. (See Stop codon.)
By inheritance
In multicellular organisms with dedicated reproductive cells, mutations can be subdivided into germline mutations, which can be
passed on to descendants through their reproductive cells, and somatic mutations (also called acquired mutations),[98] which
involve cells outside the dedicated reproductive group and which are not usually transmitted to descendants.
A germline mutation gives rise to a constitutional mutation in the offspring, that is, a mutation that is present in every cell. A
constitutional mutation can also occur very soon after fertilisation, or continue from a previous constitutional mutation in a
parent.[99]
The distinction between germline and somatic mutations is important in animals that have a dedicated germline to produce
reproductive cells. However, it is of little value in understanding the effects of mutations in plants, which lack a dedicated
germline. The distinction is also blurred in those animals that reproduce asexually through mechanisms such as budding, because
the cells that give rise to the daughter organisms also give rise to that organism's germline.
A new germline mutation not inherited from either parent is called a de novo mutation.
Diploid organisms (e.g., humans) contain two copies of each gene—a paternal
and a maternal allele. Based on the occurrence of mutation on each chromosome,
we may classify mutations into three types.
Special classes
A mutation has caused this moss
Conditional mutation is a mutation that has wild-type (or less
severe) phenotype under certain "permissive" environmental rose plant to produce flowers of
conditions and a mutant phenotype under certain "restrictive" different colors. This is a somatic
conditions. For example, a temperature-sensitive mutation can mutation that may also be passed on
cause cell death at high temperature (restrictive condition), but might in the germline.
have no deleterious consequences at a lower temperature
(permissive condition).[101] These mutations are non-autonomous,
as their manifestation depends upon presence of certain conditions,
as opposed to other mutations which appear autonomously.[102] The permissive conditions may be
temperature,[103] certain chemicals,[104] light[104] or mutations in other parts of the genome.[102] In vivo
mechanisms like transcriptional switches can create conditional mutations. For instance, association of Steroid
Binding Domain can create a transcriptional switch that can change the expression of a gene based on the
presence of a steroid ligand.[105] Conditional mutations have applications in research as they allow control over
gene expression. This is especially useful studying diseases in adults by allowing expression after a certain
period of growth, thus eliminating the deleterious effect of gene expression seen during stages of development in
model organisms.[104] DNA Recombinase systems like Cre-Lox Recombination used in association with
promoters that are activated under certain conditions can generate conditional mutations. Dual Recombinase
technology can be used to induce multiple conditional mutations to study the diseases which manifest as a result
of simultaneous mutations in multiple genes.[104] Certain inteins have been identified which splice only at certain
permissive temperatures, leading to improper protein synthesis and thus, loss of function mutations at other
temperatures.[106] Conditional mutations may also be used in genetic studies associated with ageing, as the
expression can be changed after a certain time period in the organism's lifespan.[103]
Replication timing quantitative trait loci affects DNA replication.
Nomenclature
In order to categorize a mutation as such, the "normal" sequence must be obtained from the DNA of a "normal" or "healthy"
organism (as opposed to a "mutant" or "sick" one), it should be identified and reported; ideally, it should be made publicly
available for a straightforward nucleotide-by-nucleotide comparison, and agreed upon by the scientific community or by a group
of expert geneticists and biologists, who have the responsibility of establishing the standard or so-called "consensus" sequence.
This step requires a tremendous scientific effort. Once the consensus sequence is known, the mutations in a genome can be
pinpointed, described, and classified. The committee of the Human Genome Variation Society (HGVS) has developed the
standard human sequence variant nomenclature,[107] which should be used by researchers and DNA diagnostic centers to
generate unambiguous mutation descriptions. In principle, this nomenclature can also be used to describe mutations in other
organisms. The nomenclature specifies the type of mutation and base or amino acid changes.
Nucleotide substitution (e.g., 76A>T) — The number is the position of the nucleotide from the 5' end; the first
letter represents the wild-type nucleotide, and the second letter represents the nucleotide that replaced the wild
type. In the given example, the adenine at the 76th position was replaced by a thymine.
If it becomes necessary to differentiate between mutations in genomic DNA, mitochondrial DNA, and RNA, a
simple convention is used. For example, if the 100th base of a nucleotide sequence mutated from G to C,
then it would be written as g.100G>C if the mutation occurred in genomic DNA, m.100G>C if the mutation
occurred in mitochondrial DNA, or r.100g>c if the mutation occurred in RNA. Note that, for mutations in RNA,
the nucleotide code is written in lower case.
Amino acid substitution (e.g., D111E) — The first letter is the one letter code of the wild-type amino acid, the
number is the position of the amino acid from the N-terminus, and the second letter is the one letter code of the
amino acid present in the mutation. Nonsense mutations are represented with an X for the second amino acid
(e.g. D111X).
Amino acid deletion (e.g., ΔF508) — The Greek letter Δ (delta) indicates a deletion. The letter refers to the amino
acid present in the wild type and the number is the position from the N terminus of the amino acid were it to be
present as in the wild type.
Mutation rates
Mutation rates vary substantially across species, and the evolutionary forces that generally determine mutation are the subject of
ongoing investigation.
Harmful mutations
Changes in DNA caused by mutation can cause errors in protein sequence, creating partially or completely non-functional
proteins. Each cell, in order to function correctly, depends on thousands of proteins to function in the right places at the right
times. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. Some mutations alter
a gene's DNA base sequence but do not change the function of the protein made by the gene. One study on the comparison of
genes between different species of Drosophila suggests that if a mutation does change a protein, this will probably be harmful,
with an estimated 70 percent of amino acid polymorphisms having damaging effects, and the remainder being either neutral or
weakly beneficial.[8] Studies have shown that only 7% of point mutations in noncoding DNA of yeast are deleterious and 12% in
coding DNA are deleterious. The rest of the mutations are either neutral or slightly beneficial.[108]
If a mutation is present in a germ cell, it can give rise to offspring that carries the mutation in all of its cells. This is the case in
hereditary diseases. In particular, if there is a mutation in a DNA repair gene within a germ cell, humans carrying such germline
mutations may have an increased risk of cancer. A list of 34 such germline mutations is given in the article DNA repair-
deficiency disorder. An example of one is albinism, a mutation that occurs in the OCA1 or OCA2 gene. Individuals with this
disorder are more prone to many types of cancers, other disorders and have impaired vision. On the other hand, a mutation may
occur in a somatic cell of an organism. Such mutations will be present in all descendants of this cell within the same organism,
and certain mutations can cause the cell to become malignant, and, thus, cause cancer.[109]
A DNA damage can cause an error when the DNA is replicated, and this error of replication can cause a gene mutation that, in
turn, could cause a genetic disorder. DNA damages are repaired by the DNA repair system of the cell. Each cell has a number of
pathways through which enzymes recognize and repair damages in DNA. Because DNA can be damaged in many ways, the
process of DNA repair is an important way in which the body protects itself from disease. Once DNA damage has given rise to a
mutation, the mutation cannot be repaired.
Beneficial mutations
Although mutations that cause changes in protein sequences can be harmful to an organism, on occasions the effect may be
positive in a given environment. In this case, the mutation may enable the mutant organism to withstand particular environmental
stresses better than wild-type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common
in a population through natural selection. Examples include the following:
HIV resistance: a specific 32 base pair deletion in human CCR5 (CCR5-Δ32) confers HIV resistance to homozygotes and delays
AIDS onset in heterozygotes.[110] One possible explanation of the etiology of the relatively high frequency of CCR5-Δ32 in the
European population is that it conferred resistance to the bubonic plague in mid-14th century Europe. People with this mutation
were more likely to survive infection; thus its frequency in the population increased.[111] This theory could explain why this
mutation is not found in Southern Africa, which remained untouched by bubonic plague. A newer theory suggests that the
selective pressure on the CCR5 Delta 32 mutation was caused by smallpox instead of the bubonic plague.[112]
Malaria resistance: An example of a harmful mutation is sickle-cell disease, a blood disorder in which the body produces an
abnormal type of the oxygen-carrying substance hemoglobin in the red blood cells. One-third of all indigenous inhabitants of
Sub-Saharan Africa carry the allele, because, in areas where malaria is common, there is a survival value in carrying only a single
sickle-cell allele (sickle cell trait).[113] Those with only one of the two alleles of the sickle-cell disease are more resistant to
malaria, since the infestation of the malaria Plasmodium is halted by the sickling of the cells that it infests.
Antibiotic resistance: Practically all bacteria develop antibiotic resistance when exposed to antibiotics. In fact, bacterial
populations already have such mutations that get selected under antibiotic selection.[114] Obviously, such mutations are only
beneficial for the bacteria but not for those infected.
Lactase persistence. A mutation allowed humans to express the enzyme lactase after they are naturally weaned from breast milk,
allowing adults to digest lactose, which is probably one of the most beneficial mutations in recent human evolution.[115]
Prion mutations
Prions are proteins and do not contain genetic material. However, prion replication has been shown to be subject to mutation and
natural selection just like other forms of replication.[116] The human gene PRNP codes for the major prion protein, PrP, and is
subject to mutations that can give rise to disease-causing prions.
Somatic mutation
A change in the genetic structure that is not inherited from a parent, and also not passed to offspring, is called a somatic
mutation.[98] Somatic mutations are not inherited because they do not affect the germline. These types of mutations are usually
prompted by environmental causes, such as ultraviolet radiation or any exposure to certain harmful chemicals, and can cause
diseases including cancer.[117]
With plants, some somatic mutations can be propagated without the need for seed production, for example, by grafting and stem
cuttings. These type of mutation have led to new types of fruits, such as the "Delicious" apple and the "Washington" navel
orange.[118]
Human and mouse somatic cells have a mutation rate more than ten times higher than the germline mutation rate for both species;
mice have a higher rate of both somatic and germline mutations per cell division than humans. The disparity in mutation rate
between the germline and somatic tissues likely reflects the greater importance of genome maintenance in the germline than in
the soma.[119]
Amorphic mutations
An amorph, a term utilized by Muller in 1932, is a mutated allele, which has lost the ability of the parent (whether wild type or
any other type) allele to encode any functional protein. An amorphic mutation may be caused by the replacement of an amino
acid that deactivates an enzyme or by the deletion of part of a gene that produces the enzyme.
Cells with heterozygous mutations (one good copy of gene and one mutated copy) may function normally with the unmutated
copy until the good copy has been spontaneously somatically mutated. This kind of mutation happens all the time in living
organisms, but it is difficult to measure the rate. Measuring this rate is important in predicting the rate at which people may
develop cancer.[120]
Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased
by mutagens. Mutagens can be physical, such as radiation from UV rays, X-rays or extreme heat, or chemical (molecules that
misplace base pairs or disrupt the helical shape of DNA). Mutagens associated with cancers are often studied to learn about
cancer and its prevention.
See also
Aneuploidy
Antioxidant
Budgerigar colour genetics
Ecogenetics
Embryology
Homeobox
Polyploidy
Robertsonian translocation
Signature-tagged mutagenesis
Somatic hypermutation
TILLING (molecular biology)
Trinucleotide repeat expansion
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