Editing Mutation (section)

==== 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 mutation]]s.) Small-scale mutations include:
* [[Insertion (genetics)|Insertions]] add one or more extra nucleotides into the DNA. They are usually caused by [[transposable element]]s, or errors during replication of repeating elements. Insertions in the coding region of a gene may alter [[RNA splicing|splicing]] of the [[Messenger RNA|mRNA]] ([[splice site mutation]]), or cause a shift in the [[reading frame]] ([[Frameshift mutation|frameshift]]), both of which can significantly alter the [[gene product]]. Insertions can be reversed by excision of the transposable element.
* [[Deletion (genetics)|Deletions]] 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.
* [[Point mutation|Substitution mutations]], often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another.<ref>{{cite journal | vauthors = Freese E | title = The Difference Between Spontaneous and Base-Analogue Induced Mutations of Phage T4 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 45 | issue = 4 | pages = 622–33 | date = April 1959 | pmid = 16590424 | pmc = 222607 | doi = 10.1073/pnas.45.4.622 | author-link = Ernst Freese | bibcode = 1959PNAS...45..622F | doi-access = free }}</ref> These changes are classified as transitions or transversions.<ref>{{cite journal | vauthors = Freese E | date = June 1959 |title=The specific mutagenic effect of base analogues on Phage T4 |journal=Journal of Molecular Biology |volume=1 |issue=2 |pages=87–105 |doi=10.1016/S0022-2836(59)80038-3}}</ref> 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 analogues 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 [[#By impact on protein sequence|below]], point mutations that occur within the protein [[coding region]] of a gene may be classified as [[Synonymous substitution|synonymous]] or [[nonsynonymous substitution]]s, the latter of which in turn can be divided into [[Missense mutation|missense]] or [[nonsense mutations]].