Editing Frameshift mutation (section)

{{Short description|Mutation that shifts codon alignment}}
[[File:Frameshift mutation.jpg|350px|thumb|Different types of indel mutation. Panel C is simply a deletion and not a frameshift mutation.]]

A '''frameshift mutation''' (also called a '''framing error''' or a '''reading frame shift''') is a [[genetic mutation]] caused by [[indel]]s ([[gene insertion|insertions]] or [[genetic deletion|deletions]]) of a number of [[nucleotide]]s in a DNA sequence that is not divisible by three. Due to the triplet nature of [[gene expression]] by [[codon]]s, the insertion or deletion can change the [[reading frame]] (the grouping of the codons), resulting in a completely different [[Translation (genetics)|translation]] from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein.<ref name=MBoG_6th_2008>{{cite book |last1=Losick |first1=Richard |last2=Watson |first2=James D. |first3=Tania A. |last3=Baker |last4=Bell |first4=Stephen |last5=Gann |first5=Alexander |last6=Levine |first6=Michael W. |title=Molecular biology of the gene |publisher=Pearson/Benjamin Cummings |location=San Francisco |year=2008 |isbn=978-0-8053-9592-1 |edition=6th}}</ref> A frameshift mutation is not the same as a [[single-nucleotide polymorphism]] in which a nucleotide is replaced, rather than inserted or deleted. A [[frameshift]] mutation will in general cause the reading of the codons after the mutation to code for different amino acids. The frameshift mutation will also alter the first stop codon ("UAA", "UGA" or "UAG") encountered in the sequence. The polypeptide being created could be abnormally short or abnormally long, and will most likely not be functional.<ref name="Nature Mutation">{{cite web |title=DNA Is Constantly Changing through the Process of Mutation |url=https://www.nature.com/scitable/topicpage/dna-is-constantly-changing-through-the-process-6524898 |website=Nature |access-date=17 May 2019}}</ref>

Frameshift mutations are apparent in severe genetic diseases such as [[Tay–Sachs disease]]; they increase susceptibility to certain cancers and classes of [[familial hypercholesterolaemia]]; in 1997,<ref name="HIV resistance">{{cite journal|vauthors=Zimmerman PA, Buckler-White A, Alkhatib G, Spalding T, Kubofcik J, Combadiere C, Weissman D, Cohen O, Rubbert A, Lam G, Vaccarezza M, Kennedy PE, Kumaraswami V, Giorgi JV, Detels R, Hunter J, Chopek M, Berger EA, Fauci AS, Nutman TB, Murphy PM |title = Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk.|journal = Molecular Medicine|date = January 1997|volume = 3|issue = 1|pages = 23–36|pmid = 9132277 |pmc=2230106}}</ref> a frameshift mutation was linked to resistance to infection by the HIV retrovirus. Frameshift mutations have been proposed as a source of biological novelty, as with the alleged creation of [[nylonase]], however, this interpretation is controversial. A study by Negoro ''et al.'' (2006)<ref>{{cite journal |vauthors=Negoro S, Ohki T, Shibata N, Mizuno N, Wakitani Y, Tsurukame J, Matsumoto K, Kawamoto I, Takeo M, Higuchi Y |title=X-ray crystallographic analysis of 6-aminohexanoate-dimer hydrolase: molecular basis for the birth of a nylon oligomer-degrading enzyme |journal=J Biol Chem |volume=280 |issue=47 |pages=39644–52 |date=November 2005 |pmid=16162506 |doi=10.1074/jbc.m505946200|doi-access=free }}</ref> found that a frameshift mutation was unlikely to have been the cause and that rather a two amino acid substitution in the [[active site]] of an ancestral [[esterase]] resulted in nylonase.