Changes

In [[biology]], a '''mutation''' is any physical change in the [[genetic material]] of an [[organism]]. In most cases this is either the [[DNA]] or [[RNA]] in the cell [[nucleus]]. In multicellular organisms there are two primary classes of mutation, [[germline mutations]] and [[somatic mutations]]. Germline mutations are those changes that can be passed down to offspring, while somatic mutations are mutations that only alter genetic material in the mutated organism. There is some evidence that changes outside of the cell's genetic material, such as the [[cytoplasm]], [[proteins]], or the cell [[membrane]] can also be inherited.  

In [[biology]], a '''mutation''' is any physical change in the [[genetic material]] of an [[organism]]. In most organisms, including humans, the genetic material is [[DNA]], while some viruses use [[RNA]]. Mutations can be caused by internal or external factors. In multicellular organisms there are two primary classes of mutation, [[germline mutations]] and [[somatic mutations]]. Germline mutations are those changes that can be passed down to offspring, while somatic mutations are mutations that only alter genetic material in the mutated organism. Somatic mutations are the root cause of [[cancer]]. There is some evidence that changes outside of the cell's genetic material, such as the [[cytoplasm]], [[proteins]], or the cell [[membrane]] can also be inherited.  

Mutations can be caused by internal or external factors. Common external factors include [[ultraviolet]] radiation, chemical [[mutagens]], or parasitic organisms (such as [[viruses]] or [[bacteria]]). Most internal causes of mutations stem from errors in reproduction of genetic material.  

Common external factors include [[ultraviolet]] radiation, chemical [[mutagens]], or parasitic organisms (such as [[viruses]] or [[bacteria]]). Most internal causes of mutations stem from errors in reproduction of genetic material.  

Some organisms will respond to harsh environments by increasing the rate of mutations. This is known as [[hypermutation]] and is hypothesized to aid organisms by creating wider variation in the [[gene pool]] of the population, increasing the chances that at least some descendents might survive under harsh conditions.

Some organisms will respond to harsh environments by increasing the rate of mutations. This is known as [[hypermutation]] and is hypothesized to aid organisms by creating wider variation in the [[gene pool]] of the population, increasing the chances that at least some descendents might survive under harsh conditions. Hypermutation also occurs in the human [[immune system]], so that our antibodies have more variation and can respond to a greater variety of invaders.  

==Classes of mutations==

==Classes of mutations==

A point mutation or ''substitution'' is the most limited type of mutation, whereby a single base [[nucleotide]] is replaced with another nucleotide.   

A point mutation or ''substitution'' is the most limited type of mutation, whereby a single base [[nucleotide]] is replaced with another nucleotide.   

The sickle-cell disease is caused by a single point mutation in one allele of the beta [[hemoglobin]] gene, whereby a CCT codon is converted into TCT.  The TCT then mistakenly encodes the [[amino acid]] serine instead of proline.

For example, sickle-cell anemia is caused by a single point mutation in one allele of the beta [[hemoglobin]] gene, whereby a CCT codon is converted into TCT.  The TCT then mistakenly encodes the [[amino acid]] serine instead of proline.

Sometimes the expression "point mutation" can also include the addition or subtraction of a single base pair, which is also referred to as an "indel".

Sometimes the expression "point mutation" can also include the addition or subtraction of a single base pair, which is also referred to as an "indel".

==Mutation subclasses==

==Mutation subclasses==

===Morphological===

===Morphological===

Morphological mutants affect the outward appearance of an individual. Plant height mutations could changes a tall plant to a short one, or from having smooth to round seeds.

Morphological mutants affect the outward appearance of an individual ([[phenotype]]). Plant height mutations could changes a tall plant to a short one, or from having smooth to round seeds, due to mutations in genes relating to plant growth.

===Biochemical===

===Biochemical===

Biochemical mutations have a lesion in one specific step of an enzymatic pathway. For bacteria, biochemical mutants need to be grown on a media supplemented with a specific nutrient. Such mutants are called auxotrophs. Often though, morphological mutants are the direct result of a mutation in a biochemical pathway. In humans, albinism is the result of a mutation in the pathway from converts the amino acid tyrosine to the skin pigment melanin. Similarly, cretinism results when the tyrosine to thyroxine pathway is mutated. Therefore, in a strict genetic sense, if appropriate experiments are performed, a morphological mutation can be explained at the biochemical level.

Biochemical mutations have a lesion in a gene necessary for one specific step of an enzymatic pathway. For bacteria, biochemical mutants need to be grown on a media supplemented with a specific nutrient. Such mutants are called auxotrophs. Often though, morphological mutants are the direct result of a mutation in a biochemical pathway. In humans, albinism is the result of a mutation in the pathway from converts the amino acid tyrosine to the skin pigment melanin. Similarly, cretinism results when the tyrosine to thyroxine pathway is mutated. Therefore, in a strict genetic sense, if appropriate experiments are performed, a morphological mutation can be explained at the biochemical level.

For some mutations to be expressed, the individual needs to be placed in a specific environment. This is called the restrictive condition. But if the individual grow in any other environment (permissive condition), the wild type phenotype is expressed. These are called conditional mutations. Mutations that only expressed at a specific temperature (temperature sensitive mutants), usually elevated, can be considered to be conditional mutations.

For some mutations to be expressed, the individual needs to be placed in a specific environment. This is called the restrictive condition. But if the individual grow in any other environment (permissive condition), the wild type phenotype is expressed. These are called conditional mutations. Mutations that only expressed at a specific temperature (temperature sensitive mutants), usually elevated, can be considered to be conditional mutations.

===Loss-of-function===

===Loss-of-function===

Loss-of-function mutations are typically recessive. When a heterozygote consists of the wild-type allele and the loss-of-function allele, the level of expression of the wild type allele is often sufficient to produce the wild type phenotype. Genetically this would define the loss-of-function mutation as recessive. Alternatively, the wild type allele may not compensate for the loss-of-function allele. In those cases, the phenotype of the heterozygote will be equal to that of the loss-of-function mutant, and the mutant allele will act as a dominant.

Loss-of-function mutations are typically recessive. When a heterozygote consists of the wild-type allele and the loss-of-function allele, the level of expression of the wild type allele is often sufficient to produce the wild type phenotype. Genetically this would define the loss-of-function mutation as recessive. Alternatively, the wild type allele may not compensate for the loss-of-function allele, and the gene is called haploinsufficient. In those cases, the phenotype of the heterozygote may be equal to that of the loss-of-function mutant, and the mutant allele will act as a dominant.

===Gain-of-function===

===Gain-of-function===

Gain-of-function mutations create a new allele that is associated with a new function. Any heterozygote containing the new allele along with the original wild type allele will express the new allele. Genetically this will define the mutation as a dominant.

Gain-of-function mutations create a new allele that is associated with a new function. Any heterozygote containing the new allele along with the original wild type allele will express the new allele. Genetically this will define the mutation as a dominant.

'''Sickle hemoglobin''', where the function of the hemoglobin has changed in a way to be not conducive to [[malaria]] [[parasite]]s, is often cited as an example of a gain-of-function mutation, but it is actually a loss-of-function mutation that conveys a survival advantage in some circumstances.

'''Sickle hemoglobin''', where the function of the hemoglobin has changed in a way to be not conducive to [[malaria]] [[parasite]]s, is often cited as an example of a gain-of-function mutation, but it is actually a loss-of-function mutation that conveys a survival advantage in some circumstances. A proper example is the mutations that occur in the immune system in order to make and improve antibodies against invading bacteria and viruses.  

{{QuoteBox|This is good evidence that natural selection plays a part in maintaining a higher frequency of this carrier state. If you are resistant to malaria, you are more likely to survive to pass on your genes. Nevertheless, it is a defect, not an increase in complexity or an improvement in function which is being selected for, and having more carriers in the population means that there will be more people suffering from this terrible [[disease]].<ref>[http://www.creationontheweb.com/content/view/901/ Sickle-cell anemia does not prove evolution!], ''Creation'' 16(2):40–41, March 1994.</ref>}}

{{QuoteBox|This is good evidence that natural selection plays a part in maintaining a higher frequency of this carrier state. If you are resistant to malaria, you are more likely to survive to pass on your genes. Nevertheless, it is a defect, not an increase in complexity or an improvement in function which is being selected for, and having more carriers in the population means that there will be more people suffering from this terrible [[disease]].<ref>[http://www.creationontheweb.com/content/view/901/ Sickle-cell anemia does not prove evolution!], ''Creation'' 16(2):40–41, March 1994.</ref>}}

'''HIV-1 M subtype D's Na+ viroporin''', is known as an example of a Gain-of-Function mutation due to the viroporin being gated and specific to Na+ cations.  A viroporin is an ion channel that allows for the movement of ions from one side of a membrane to another.  A gated channel has an additional feature which closes the channel to prevent "leaking" of ions across the membrane.  In this example the HIV types before HIV-1 M did not have this viroporin.  To go from an ordinary viroporin's original form to the multisubunit structure with a new function required the development of a new binding site, which involves more than a single amino acid substitution<ref>Paul et al. (1998) Mutational Analysis of the Human Immunodeficiency Virus Type 1 Vpu Transmembrane Domain That Promotes the Enhanced Release of Virus-Like Particles from the Plasma Membrane of Mammalian Cells. J Virol, 72 (2): 1270.</ref>. Not just any binding site will do, for a mass of agglomerated protein would occur, not an ion channel with ion selectivity. As such, HIV-1 M's viroporin is a gated ion channel, not just a hole punched in the membrane, with a specific amino acid responsible for the gating<ref>Mehnert T, et al., Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism. Proteins. 2007 Oct 1; doi: 10.1002/prot.21642.</ref>. What is important is that this mutation is beneficial to the virus; it increases viral particle release, spreading HIV more efficiently<ref>Paul et al. (1998) Mutational Analysis of the Human Immunodeficiency Virus Type 1 Vpu Transmembrane Domain That Promotes the Enhanced Release of Virus-Like Particles from the Plasma Membrane of Mammalian Cells. J Virol, 72 (2): 1270.</ref>.

'''HIV-1 M subtype D's Na+ viroporin''', is known as an example of a Gain-of-Function mutation due to the viroporin being gated and specific to Na+ cations.  A viroporin is an ion channel that allows for the movement of ions from one side of a membrane to another.  A gated channel has an additional feature which closes the channel to prevent "leaking" of ions across the membrane.  In this example the HIV types before HIV-1 M did not have this viroporin.  To go from an ordinary viroporin's original form to the multisubunit structure with a new function required the development of a new binding site, which involves more than a single amino acid substitution<ref>Paul et al. (1998) Mutational Analysis of the Human Immunodeficiency Virus Type 1 Vpu Transmembrane Domain That Promotes the Enhanced Release of Virus-Like Particles from the Plasma Membrane of Mammalian Cells. J Virol, 72 (2): 1270.</ref>. Not just any binding site will do, for a mass of agglomerated protein would occur, not an ion channel with ion selectivity. As such, HIV-1 M's viroporin is a gated ion channel, not just a hole punched in the membrane, with a specific amino acid responsible for the gating<ref>Mehnert T, et al., Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism. Proteins. 2007 Oct 1; doi: 10.1002/prot.21642.</ref>. What is important is that this mutation is beneficial to the virus; it increases viral particle release, spreading HIV more efficiently<ref>Paul et al. (1998) Mutational Analysis of the Human Immunodeficiency Virus Type 1 Vpu Transmembrane Domain That Promotes the Enhanced Release of Virus-Like Particles from the Plasma Membrane of Mammalian Cells. J Virol, 72 (2): 1270.</ref>.

===Dynamic mutation===

Dynamic mutations are heritable mutations where the probability of the mutation is a function of the number of copies of the mutation, causing the chance of inheriting the mutation to be different than organism’s predecessor. These mutations are known to cause several genetic syndromes such as [[Fragile X syndrome]], Huntington’s Chorea, Myotonic Dystrophy and Creutzfeldt-Jakob Disease to name a few.

 

 

 

 

===Dynamic===

Dynamic mutations are heritable mutations where the probability of the mutation is a function of the number of copies of the mutation, causing the chance of inheriting the mutation to be different than organism’s predecessor. These mutations are known to cause several genetic syndromes such as [[Fragile X syndrome]], Huntington’s Chorea, Myotonic Dystrophy and Creutzfeldt-Jakob Disease to name a few.  

===Frame shift mutation===

===Frame shift===

Frame shift mutations are mutations where the reading frame is moved to cause a different translation of the DNA.  This is due to the fact that codons that encode the genetic sequence are read in threes.  Frame shift mutations are known to cause hypercholesterolemia as well as disabling several chemokine receptors.

Frame shift mutations are mutations where the reading frame is moved to cause a different translation of the DNA.  This is due to the fact that codons that encode the genetic sequence are read in threes.  Frame shift mutations are known to cause hypercholesterolemia as well as disabling several chemokine receptors.

==Mutations and the Theory of Evolution==

==Mutations and the Theory of Evolution==