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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.
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==Evolution as a theory and a fact==
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==Types of Mutations==
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The terms fact and theory can be applied to evolution, just as they are to gravity.[1] Misuse and misunderstanding of how those terms are applied to evolution have been used to construct arguments disputing the validity of evolution.
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DNA is not a static enity.  It is subject to a variety of different types of heritable change (mutation).  Large-scale chromosome abnormalities involve loss or gain of chromosomes, or breakage and rejoining of chromatids.  Smaller scale mutations can be grouped into different mutation classes according to the effect on the DNA sequence. Mutations can also be categorized on the basis of whether they involve a single DNA sequence or whether they involve exchanges between two allelic or nonallelic sequences.  
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In the study of biological species, the facts include fossils and measurements of these fossils. The location of a fossil is an example of a fact (using the scientific meaning of the word fact). In species that rapidly reproduce, for example fruit flies, the process of evolutionary change has been observed in the laboratory.[18] The observation of fruit fly populations changing character is also an example of a fact, using the scientific meaning of the word fact. So evolution is a fact, at least using the scientific meaning of the word fact. These facts require an explanation, just as the observations of gravity did.
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===Morphological mutants===
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In biology, there have been many attempts to explain these observations over the years. Lamarckism, Transmutationism and Orthogenesis were all non-Darwinian theories that attempted to explain the observations of species and fossils and other evidence. However, the Theory of Evolution is the explanation for all relevant observations regarding the development of life, based on a model that explains all the available data and observations. Thus, evolution is not only a fact but also a theory, just as gravity is both a fact and a theory.
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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.
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===Biochemical mutations===
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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.
!style="background:#d0e5f5;color:black" |Gravity!!style="background:#d0e5f5;color:black" |Evolution
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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.
|Things falling is an observation of the pull of bodies towards each other.||Fruit flies changing generation to generation is an observation of generational organism change.  
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===Lethal mutations===
|Bodies pulling towards each other is called gravity.||Organisms changing generation to generation is called evolution.  
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Lethal mutations are mutations that lead to the death of the individual. Death does not have to occur immediately, it may take several months or even years. But if the expected longevity of an individual is significantly reduced, the mutation is considered a lethal mutation.  
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|Gravity is a fact.||Evolution is a fact.
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Wild type alleles typically encode a product necessary for a specific biological function. If a mutation occurs in that allele, the function for which it encodes is also lost. The general term for these mutations is loss-of-function mutations. The degree to which the function is lost can vary. If the function is entirely lost, the mutation is called a null mutation. If is also possible that some function may remain, but not at the level of the wild type allele. These are called leaky mutations.  
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!style="background:#d0e5f5;color:black" |An explanation for the facts of gravity.!!style="background:#d0e5f5;color:black" |An explanation for the facts of evolution.
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===Loss-of-function mutations===
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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.
|[[Aristotle]] and [[Galileo]] created explanations of the ''fact'' of gravity. These are now obsolete explanations. ||[[Lamarckism]], [[Transmutationism]] and [[Orthogenesis]] were created as explanations of the fact of evolution. These are now discredited explanations.  
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===Gain-of-function mutations===
|[[Isaac Newton|Newton's]] explanation of gravity is approximately correct but required refinement.||[[Charles Darwin|Darwin's]] explanation of evolution is approximately correct, but required refinement.
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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.
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|[[Einstein]]'s explanation is a refinement of Newton's explanation of gravity. Einstein's explanation is currently the most accepted explanation of the fact of gravity. || The [[modern evolutionary synthesis]] is a refinement of Darwin's explanation of evolution. This modern synthesis is currently the most accepted explanation of the fact of evolution.
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'''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.
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|Einstein's explanation of the fact of gravity is called ''The General theory of relativity''. ||The explanation of the fact of evolution provided by the modern synthesis is the latest and most widely accepted ''Theory of Evolution''.
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{{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>}}
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!style="background:#d0e5f5;color:black" |Gravity is a fact and a theory.!!style="background:#d0e5f5;color:black" |Evolution is a fact and a theory.
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'''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>.
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==Mutatations and the Theory of Evolution==
 
==Mutatations and the Theory of Evolution==
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