functional divergence

{{Short description|Process by which genes shift in function}}

Functional divergence is the process by which genes, after gene duplication, shift in function from an ancestral function. Functional divergence can result in either subfunctionalization, where a paralog specializes one of several ancestral functions, or neofunctionalization, where a totally new functional capability evolves. It is thought that this process of gene duplication and functional divergence is a major originator of molecular novelty and has produced the many large protein families that exist today.{{cite book | last1 = Gu | first1 = X | chapter = Functional divergence in protein (Family) sequence evolution | date = Jul 2003 | title = Origin and Evolution of New Gene Functions | journal = Genetica | volume = 118 | issue = 2–3| pages = 133–41 | doi=10.1007/978-94-010-0229-5_4| pmid = 12868604 | series = Contemporary Issues in Genetics and Evolution | isbn = 978-94-010-3982-6 }}{{cite journal | last1 = Fay | first1 = JC | last2 = Wu | first2 = CI | year = 2003 | title = Sequence divergence, functional constraint, and selection in protein evolution | journal = Annu Rev Genom Hum Genet | volume = 4 | pages = 213–35 | doi = 10.1146/annurev.genom.4.020303.162528 | pmid = 14527302 | doi-access = free }}

Functional divergence is just one possible outcome of gene duplication events. Other fates include nonfunctionalization where one of the paralogs acquires deleterious mutations and becomes a pseudogene and superfunctionalization (reinforcement),{{cite journal | last1 = Dvornyk | first1 = V | last2 = Vinogradova | first2 = ON | last3 = Nevo | first3 = E | year = 2002 | title = Long-term microclimatic stress causes rapid adaptive radiation of kaiABC clock gene family in a cyanobacterium, Nostoc linckia, from "Evolution Canyons" I and II, Israel | journal = Proc Natl Acad Sci USA | volume = 99 | issue = 4| pages = 2082–2087 | doi=10.1073/pnas.261699498 | pmid=11842226 | pmc=123721| bibcode = 2002PNAS...99.2082D | doi-access = free }} where both paralogs maintain original function. While gene, chromosome, or whole genome duplication events are considered the canonical sources of functional divergence of paralogs, orthologs (genes descended from speciation events) can also undergo functional divergence {{cite journal | last1 = Studer | first1 = RA | last2 = Robinson-Rechavi | first2 = M | year = 2009 | title = How confident can we be that orthologs are similar, but paralogs differ? | url = https://serval.unil.ch/notice/serval:BIB_39F8106EE698| journal = Trends in Genetics | volume = 25 | issue = 5| pages = 210–6 | doi = 10.1016/j.tig.2009.03.004 | pmid=19368988}}{{cite journal | last1 = Studer | last2 = Robinson-Rechavi | first2 = M | year = 2010 | title = Large-scale analysis of orthologs and paralogs under covarion-like and constant-but-different models of amino acid evolution | journal = Molecular Biology and Evolution | volume = 27 | issue = 11| pages = 2618–2627 | doi = 10.1093/molbev/msq149 | pmid=20551039 | pmc=2955734}}{{cite journal | last1 = Gharib | first1 = WH | last2 = Robinson-Rechavi | first2 = M | year = 2011 | title = When orthologs diverge between human and mouse | journal = Briefings in Bioinformatics | volume = 12 | issue = 5| pages = 436–441 | doi = 10.1093/bib/bbr031 | pmid = 21677033 | pmc = 3178054 }}{{cite journal | last1 = Nehrt | first1 = NL | last2 = Clark | first2 = WT | last3 = Radivojac | first3 = P | last4 = Hahn | first4 = MW | year = 2011 | title = Testing the ortholog conjecture with comparative functional genomic data from mammals | journal = PLOS Computational Biology | volume = 7 | issue = 6| page = e1002073 | doi = 10.1371/journal.pcbi.1002073 | pmid=21695233 | pmc=3111532| bibcode = 2011PLSCB...7E2073N | doi-access = free }} and horizontal gene transfer can also result in multiple copies of a gene in a genome, providing the opportunity for functional divergence.

Many well known protein families are the result of this process, such as the ancient gene duplication event that led to the divergence of hemoglobin and myoglobin, the more recent duplication events that led to the various subunit expansions (alpha and beta) of vertebrate hemoglobins,{{cite journal | last1 = Storz | first1 = Jay F. | last2 = Hoffmann | first2 = Federico G. | last3 = Opazo | first3 = Juan C. | last4 = Moriyama | first4 = Hideaki | date = March 2008 | title = Adaptive Functional Divergence Among Triplicated α-Globin Genes in Rodents | journal = Genetics | volume = 178 | issue = 3| pages = 1623–1638 | doi = 10.1534/genetics.107.080903 | pmid = 18245844 | pmc = 2278084 }} or the expansion of G-protein alpha subunits {{cite journal | last1 = Zheng | first1 = Y | last2 = Xu | first2 = D | last3 = Gu | first3 = X | year = 2007 | title = Functional divergence after gene duplication and sequence-structure relationship: a case study of G-protein alpha subunits | url = https://lib.dr.iastate.edu/rtd/15063| journal = Journal of Experimental Zoology Part B: Molecular and Developmental Evolution | volume = 308 | issue = 1| pages = 85–96 | doi = 10.1002/jez.b.21140 | pmid = 17094082 | doi-access = free }}