for: Introduction to genetics For: Apophony For: Mutation (disambiguation)

Mutations create variation within the gene pool. Less favorable (or deleterious) mutations can be reduced in frequency in the gene pool by natural selection, while more favorable (beneficial or advantageous) mutations may accumulate and result in adaptive evolutionary 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 chance of this butterfly 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 accumulate over time due to genetic drift. It is believed that the overwhelming majority of mutations have no significant effect on an organism's fitness. 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.

Mutation is generally accepted by the scientific community as the mechanism upon which natural selection acts, providing the advantageous new traits that survive and multiply in offspring or disadvantageous traits that die out with weaker organisms.

By effect on structure

• Small-scale mutations, such those as affecting a small gene in one or a few nucleotides, including:
• Point mutations, often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another. 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 mis-pairing, or mutagenic base analogs such as 5-bromo-2-deoxyuridine (BrdU). Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). 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). These changes are classified as transitions or transversions. An example of a transversion is adenine (A) being converted into a cytosine (C). There are also many other examples that can be found. Point mutations that occur within the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for:
• Silent mutations: which code for the same amino acid.
• Missense mutations: which code for a different amino acid.
• Nonsense mutations: which code for a stop and can truncate the protein.
• Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). 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 reverted by excision of the transposable element.
• Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are generally irreversible: though exactly the same sequence might theoretically be restored by an insertion, transposable elements able to revert a very short deletion (say 1–2 bases) in any location are either highly unlikely to exist or do not exist at all. Note that a deletion is not the exact opposite of an insertion: the former is quite random while the latter consists of a specific sequence inserting at locations that are not entirely random or even quite narrowly defined.
• Large-scale mutations in chromosomal structure, including:
• Amplifications (or gene duplications) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
• Deletions of large chromosomal regions, leading to loss of the genes within those regions.
• Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:
• Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
• Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
• Chromosomal inversions: reversing the orientation of a chromosomal segment.
• Loss of heterozygosity: loss of one allele, either by a deletion or recombination event, in an organism that previously had two different alleles.