Editing Mutation (section)

==== Experiment in virus ====
Gong et al.<ref>{{Cite journal |last1=Gong |first1=Lizhi Ian |last2=Suchard |first2=Marc A |last3=Bloom |first3=Jesse D |date=14 May 2013 |editor-last=Pascual |editor-first=Mercedes |title=Stability-mediated epistasis constrains the evolution of an influenza protein |journal=eLife |volume=2 |pages=e00631 |doi=10.7554/eLife.00631 |issn=2050-084X |pmc=3654441 |pmid=23682315 |doi-access=free }}</ref> collected obtained genotype data of influenza nucleoprotein from different timelines and temporally ordered them according to their time of origin. Then they isolated 39 amino acid substitutions that occurred in different timelines and substituted them in a genetic background that approximated the ancestral genotype. They found that 3 of the 39 substitutions significantly reduced the fitness of the ancestral background. Compensatory mutations are new mutations that arise and have a positive or neutral impact on a populations fitness.<ref name="Davis-2009">{{Cite journal |last1=Davis |first1=Brad H. |last2=Poon |first2=Art F.Y. |last3=Whitlock |first3=Michael C. |date=22 May 2009 |title=Compensatory mutations are repeatable and clustered within proteins |journal=Proceedings of the Royal Society B: Biological Sciences |volume=276 |issue=1663 |pages=1823–1827 |doi=10.1098/rspb.2008.1846 |issn=0962-8452 |pmc=2674493 |pmid=19324785}}</ref> Previous research has shown that populations have can compensate detrimental mutations.<ref name="Barešić-2011"/><ref name="Davis-2009" /><ref>{{Cite journal |last1=Azbukina |first1=Nadezhda |last2=Zharikova |first2=Anastasia |last3=Ramensky |first3=Vasily |date=1 October 2022 |title=Intragenic compensation through the lens of deep mutational scanning |url=https://doi.org/10.1007/s12551-022-01005-w |journal=Biophysical Reviews |language=en |volume=14 |issue=5 |pages=1161–1182 |doi=10.1007/s12551-022-01005-w |issn=1867-2469 |pmc=9636336 |pmid=36345285}}</ref> Burch and Chao tested [[Fisher's geometric model]] of adaptive evolution by testing whether bacteriophage φ6 evolves by small steps.<ref name="Burch-1999">{{Cite journal |last1=Burch |first1=Christina L |last2=Chao |first2=Lin |date=1 March 1999 |title=Evolution by Small Steps and Rugged Landscapes in the RNA Virus ϕ6 |url=https://academic.oup.com/genetics/article/151/3/921/6034699 |journal=Genetics |language=en |volume=151 |issue=3 |pages=921–927 |doi=10.1093/genetics/151.3.921 |issn=1943-2631 |pmc=1460516 |pmid=10049911}}</ref> Their results showed that [[bacteriophage]] φ6 fitness declined rapidly and recovered in small steps .<ref name="Burch-1999" /> Viral nucleoproteins have been shown to avoid cytotoxic T lymphocytes (CTLs) through arginine-to glycine substitutions.<ref name="Rimmelzwaan-2005">{{Cite journal |last1=Rimmelzwaan |first1=G. F. |last2=Berkhoff |first2=E. G. M. |last3=Nieuwkoop |first3=N. J. |last4=Smith |first4=D. J. |last5=Fouchier |first5=R. A. M. |last6=Osterhaus |first6=A. D. M. E.YR 2005 |title=Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants |journal=Journal of General Virology |year=2005 |volume=86 |issue=6 |pages=1801–1805 |doi=10.1099/vir.0.80867-0 |pmid=15914859 |issn=1465-2099|doi-access=free |hdl=1765/8466 |hdl-access=free }}</ref> This substitution mutations impacts the fitness of viral nucleoproteins, however compensatory co-mutations impede fitness declines and aid the virus to avoid recognition from CTLs.<ref name="Rimmelzwaan-2005" /> Mutations can have three different effects; mutations can have deleterious effects, some increase fitness through compensatory mutations, and lastly mutations can be counterbalancing resulting in compensatory neutral mutations.<ref>{{Cite journal |last=Kimura |first=Motoo |date=1 July 1985 |title=The role of compensatory neutral mutations in molecular evolution |url=https://doi.org/10.1007/BF02923549 |journal=Journal of Genetics |language=en |volume=64 |issue=1 |pages=7–19 |doi=10.1007/BF02923549 |s2cid=129866 |issn=0973-7731}}</ref><ref name="Reynolds-2000" /><ref name="Gagneux-2006" />