Editing Molecular evolution (section)

==Gene family evolution==
{{main|Gene family}}

[[File:Ortholog paralog analog examples.svg|thumb|400x400px|Gene [[Phylogenetic tree|phylogeny]] as lines within grey species phylogeny. Top: An ancestral [[gene duplication]] produces two paralogs ([[histone H1.1]] and [[Histone H1.2|1.2]]). A speciation event produces orthologs in the two daughter species (human and chimpanzee). Bottom: in a separate species ([[E. coli]]), a gene has a similar function ([[histone-like nucleoid-structuring protein]]) but has a separate evolutionary origin and so is an [[Analogy (biology)|analog]].]]

[[Gene duplication]] can produce multiple [[Sequence homology|homologous]] proteins (paralogs) within the same species. [[Phylogenetics|Phylogenetic]] analysis of proteins has revealed how proteins evolve and change their structure and function over time.<ref name="2017-Hanukoglu-b">{{cite journal | vauthors = Hanukoglu I | title = ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters | journal = The FEBS Journal | volume = 284 | issue = 4 | pages = 525–545 | date = February 2017 | pmid = 27580245 | doi = 10.1111/febs.13840 | s2cid = 24402104 | url = https://zenodo.org/record/890906 }}</ref><ref name="2016-Hanukoglu">{{cite journal | vauthors = Hanukoglu I, Hanukoglu A | title = Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases | journal = Gene | volume = 579 | issue = 2 | pages = 95–132 | date = April 2016 | pmid = 26772908 | pmc = 4756657 | doi = 10.1016/j.gene.2015.12.061 }}</ref>

For example, [[ribonucleotide reductase]] (RNR) has evolved a multitude of structural and functional variants. '''Class I''' RNRs use a [[ferritin]] subunit and differ by the metal they use as cofactors. In '''class II''' RNRs, the [[thiyl radical]] is generated using an [[adenosylcobalamin]] cofactor and these enzymes do not require additional subunits (as opposed to class I which do). In '''class III''' RNRs, the thiyl radical is generated using [[S-Adenosyl methionine|S-adenosylmethionine]] bound to a [<nowiki/>[[Iron-sulfur protein|4Fe-4S]]] cluster. That is, within a single family of proteins numerous structural and functional mechanisms can evolve.<ref>{{cite journal | vauthors = Burnim AA, Spence MA, Xu D, Jackson CJ, Ando N | title = Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade | journal = eLife | volume = 11 | pages = e79790 | date = September 2022 | pmid = 36047668|pmc=9531940|doi = 10.7554/eLife.79790 | veditors = Ben-Tal N, Weigel D, Ben-Tal N, Stubbe J, Hofer A | doi-access = free }}</ref>

In a proof-of-concept study, Bhattacharya and colleagues converted [[myoglobin]], a non-enzymatic oxygen storage protein, into a highly efficient [[Benzisoxazole|Kemp eliminase]] using only three [[mutation]]s. This demonstrates that only few mutations are needed to radically change the function of a protein.<ref>{{cite journal | vauthors = Bhattacharya S, Margheritis EG, Takahashi K, Kulesha A, D'Souza A, Kim I, Yoon JH, Tame JR, Volkov AN, Makhlynets OV, Korendovych IV | display-authors = 6 | title = NMR-guided directed evolution | journal = Nature | volume = 610 | issue = 7931 | pages = 389–393 | date = October 2022 | pmid = 36198791 | doi = 10.1038/s41586-022-05278-9 | pmc = 10116341 | bibcode = 2022Natur.610..389B | s2cid = 245067145 }}</ref> [[Directed evolution]] is the attempt to engineer proteins using methods inspired by molecular evolution.