Editing Missense mutation (section)

== Evolution ==
[[File:Phylogenetic_tree_of_SNP_variations.png|thumb|Diverged nucleotide sequence demonstrating how sequences diverge over time. Red letters are nucleotides changed from the original sequence.]]
If a missense mutation is not deleterious, it will not be selected against and can contribute to [[Divergent evolution|species divergence]].<ref>{{Cite journal |last1=Kryukov |first1=Gregory V. |last2=Pennacchio |first2=Len A. |last3=Sunyaev |first3=Shamil R. |date=April 2007 |title=Most Rare Missense Alleles Are Deleterious in Humans: Implications for Complex Disease and Association Studies |journal=The American Journal of Human Genetics |language=en |volume=80 |issue=4 |pages=727–739 |doi=10.1086/513473 |pmc=1852724 |pmid=17357078}}</ref><ref>{{Cite journal |last1=Koref |first1=M.F. Santibáñez |last2=Gangeswaran |first2=R. |last3=Koref |first3=I.P. Santibáñez |last4=Shanahan |first4=N. |last5=Hancock |first5=J.M. |date=July 2003 |title=A phylogenetic approach to assessing the significance of missense mutations in disease genes |url=https://onlinelibrary.wiley.com/doi/10.1002/humu.10235 |journal=Human Mutation |language=en |volume=22 |issue=1 |pages=51–58 |doi=10.1002/humu.10235 |issn=1059-7794 |pmid=12815593|url-access=subscription }}</ref> Over time, mutations occur randomly in individuals and can become [[Fixation (population genetics)|fixed]] in populations if they are not selected against.<ref>{{Cite journal |last1=Zhang |first1=Guojie |last2=Pei |first2=Zhang |last3=Krawczak |first3=Michael |last4=Ball |first4=Edward V. |last5=Mort |first5=Matthew |last6=Kehrer-Sawatzki |first6=Hildegard |last7=Cooper |first7=David N. |date=December 2010 |title=Triangulation of the human, chimpanzee, and Neanderthal genome sequences identifies potentially compensated mutations |url=https://onlinelibrary.wiley.com/doi/10.1002/humu.21389 |journal=Human Mutation |language=en |volume=31 |issue=12 |pages=1286–1293 |doi=10.1002/humu.21389 |pmid=21064102}}</ref> Missense mutations are a type of mutation that are not [[Neutral mutation|neutral]], and therefore can be acted on by selection. Selection cannot act on synonymous mutations (mutations that do not change anything phenotypically).<ref>{{Cite journal |last1=Shen |first1=Xukang |last2=Song |first2=Siliang |last3=Li |first3=Chuan |last4=Zhang |first4=Jianzhi |date=2022-06-23 |title=Synonymous mutations in representative yeast genes are mostly strongly non-neutral |journal=Nature |language=en |volume=606 |issue=7915 |pages=725–731 |bibcode=2022Natur.606..725S |doi=10.1038/s41586-022-04823-w |issn=0028-0836 |pmc=9650438 |pmid=35676473}}</ref>

Tracking missense mutations, like nonsynonymous SNPs, in ancestral species populations allow genealogies and phylogenetic trees to be created and evolutionary connections to be made.<ref>{{Cite journal |last1=Hajdu |first1=Anita |last2=Nyári |first2=Dóra Vivien |last3=Ádám |first3=Éva |last4=Kim |first4=Yeon Jeong |last5=Somers |first5=David E. |last6=Silhavy |first6=Dániel |last7=Nagy |first7=Ferenc |last8=Kozma-Bognár |first8=László |date=2024-10-25 |title=Forward genetic approach identifies a phylogenetically conserved serine residue critical for the catalytic activity of UBIQUITIN-SPECIFIC PROTEASE 12 in Arabidopsis |journal=Scientific Reports |language=en |volume=14 |issue=1 |page=25273 |doi=10.1038/s41598-024-77232-w |issn=2045-2322 |pmc=11511944 |pmid=39455703|bibcode=2024NatSR..1425273H }}</ref> Missense mutation analysis is often used in evolutionary genetics to create relationships between species, as amino acid changes leading to protein changes are needed for species to diverge from each other.<ref>{{Cite journal |last1=Teixeira |first1=João C. |last2=de Filippo |first2=Cesare |last3=Weihmann |first3=Antje |last4=Meneu |first4=Juan R. |last5=Racimo |first5=Fernando |last6=Dannemann |first6=Michael |last7=Nickel |first7=Birgit |last8=Fischer |first8=Anne |last9=Halbwax |first9=Michel |last10=Andre |first10=Claudine |last11=Atencia |first11=Rebeca |last12=Meyer |first12=Matthias |last13=Parra |first13=Genís |last14=Pääbo |first14=Svante |last15=Andrés |first15=Aida M. |date=May 2015 |title=Long-Term Balancing Selection in LAD1 Maintains a Missense Trans-Species Polymorphism in Humans, Chimpanzees, and Bonobos |url=https://academic.oup.com/mbe/article-lookup/doi/10.1093/molbev/msv007 |journal=Molecular Biology and Evolution |language=en |volume=32 |issue=5 |pages=1186–1196 |doi=10.1093/molbev/msv007 |pmid=25605789 |issn=1537-1719}}</ref>