Editing Epigenetics (section)

===Transgenerational===
{{main|Transgenerational epigenetic inheritance}}
<!--Note that the first sentence of this section clashes with the first sentence of the article defining 'epigenetics', by which epigenetics is necessarily heritable. This may arise from confusing the molecular marks sometimes associated with epigenetic variation (e.g. DNA methylation) with epigenetic phenotypic variation itself.-->
Epigenetic mechanisms were a necessary part of the evolutionary origin of [[cell differentiation]].<ref name="isbn0-19-854968-7">{{cite book | vauthors = Hoekstra RF | title = Evolution: an introduction | publisher = Oxford University Press | location = Oxford | year = 2000 | page = 285 | isbn = 978-0-19-854968-0 }}</ref>{{request quotation|date=November 2020}} Although epigenetics in multicellular organisms is generally thought to be a mechanism involved in differentiation, with epigenetic patterns "reset" when organisms reproduce, there have been some observations of transgenerational epigenetic inheritance (e.g., the phenomenon of [[paramutation]] observed in [[maize]]). Although most of these multigenerational epigenetic traits are gradually lost over several generations, the possibility remains that multigenerational epigenetics could be another aspect to [[evolution]] and adaptation.
As mentioned above, some define epigenetics as heritable.

A sequestered germ line or [[Weismann barrier]] is specific to animals, and epigenetic inheritance is more common in plants and microbes. [[Eva Jablonka]], [[Marion J. Lamb]] and Étienne Danchin have argued that these effects may require enhancements to the standard conceptual framework of the [[modern synthesis (20th century)|modern synthesis]] and have called for an [[extended evolutionary synthesis]].<ref name="isbn0-262-10107-6">{{cite book |vauthors= Lamb MJ, Jablonka E | title= Evolution in four dimensions: genetic, epigenetic, behavioral, and symbolic variation in the history of life | publisher= MIT Press | location= Cambridge, Massachusetts | year= 2005 | isbn= 978-0-262-10107-3 }}</ref><ref>See also [[Denis Noble]]: ''The Music of Life'', esp pp. 93–98 and p. 48, where he cites Jablonka & Lamb and [[Massimo Pigliucci]]'s review of Jablonka and Lamb in [[Nature (journal)|''Nature'']] '''435''', 565–566 (2 June 2005)</ref><ref>{{cite journal | vauthors = Danchin É, Charmantier A, Champagne FA, Mesoudi A, Pujol B, Blanchet S | title = Beyond DNA: integrating inclusive inheritance into an extended theory of evolution | journal = Nature Reviews. Genetics | volume = 12 | issue = 7 | pages = 475–86 | date = June 2011 | pmid = 21681209 | doi = 10.1038/nrg3028 | s2cid = 8837202 }}</ref> Other evolutionary biologists, such as [[John Maynard Smith]], have incorporated epigenetic inheritance into [[population genetics|population-genetics]] models<ref>{{cite journal | vauthors = Maynard Smith J | title = Models of a dual inheritance system | journal = Journal of Theoretical Biology | volume = 143 | issue = 1 | pages = 41–53 | date = March 1990 | pmid = 2359317 | doi = 10.1016/S0022-5193(05)80287-5 | bibcode = 1990JThBi.143...41M }}</ref> or are openly skeptical of the extended evolutionary synthesis ([[Michael Lynch (geneticist)|Michael Lynch]]).<ref>{{cite journal | vauthors = Lynch M | title = The frailty of adaptive hypotheses for the origins of organismal complexity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = Suppl 1 | pages = 8597–604 | date = May 2007 | pmid = 17494740 | pmc = 1876435 | doi = 10.1073/pnas.0702207104 | bibcode = 2007PNAS..104.8597L | doi-access = free }}</ref> Thomas Dickins and Qazi Rahman state that epigenetic mechanisms such as DNA methylation and histone modification are genetically inherited under the control of [[natural selection]] and therefore fit under the earlier [[Modern synthesis (20th century)|"modern synthesis"]].<ref>{{cite journal | vauthors = Dickins TE, Rahman Q | title = The extended evolutionary synthesis and the role of soft inheritance in evolution | journal = Proceedings. Biological Sciences | volume = 279 | issue = 1740 | pages = 2913–21 | date = August 2012 | pmid = 22593110 | pmc = 3385474 | doi = 10.1098/rspb.2012.0273 }}</ref>

Two important ways in which epigenetic inheritance can differ from traditional genetic inheritance, with important consequences for evolution, are:
* rates of epimutation can be much faster than rates of mutation<ref name=rando_and_verstrepen>{{cite journal | vauthors = Rando OJ, Verstrepen KJ | title = Timescales of genetic and epigenetic inheritance | journal = Cell | volume = 128 | issue = 4 | pages = 655–68 | date = February 2007 | pmid = 17320504 | doi = 10.1016/j.cell.2007.01.023 | s2cid = 17964015 | doi-access = free }}</ref>
* the epimutations are more easily reversible<ref>{{cite journal | vauthors = Lancaster AK, Masel J | title = The evolution of reversible switches in the presence of irreversible mimics | journal = Evolution; International Journal of Organic Evolution | volume = 63 | issue = 9 | pages = 2350–62 | date = September 2009 | pmid = 19486147 | pmc = 2770902 | doi = 10.1111/j.1558-5646.2009.00729.x }}</ref>

In plants, heritable DNA methylation mutations are 100,000 times more likely to occur compared to DNA mutations.<ref name=van_der_Graaf_et_al>{{cite journal | vauthors = van der Graaf A, Wardenaar R, Neumann DA, Taudt A, Shaw RG, Jansen RC, Schmitz RJ, Colomé-Tatché M, Johannes F | title = Rate, spectrum, and evolutionary dynamics of spontaneous epimutations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 21 | pages = 6676–81 | date = May 2015 | pmid = 25964364 | pmc = 4450394 | doi = 10.1073/pnas.1424254112 | bibcode = 2015PNAS..112.6676V | doi-access = free }}</ref> An epigenetically inherited element such as the [[PSI (prion)|PSI+]] system can act as a "stop-gap", good enough for short-term adaptation that allows the lineage to survive for long enough for mutation and/or recombination to [[genetic assimilation|genetically assimilate]] the adaptive phenotypic change.<ref>{{cite journal | vauthors = Griswold CK, Masel J | title = Complex adaptations can drive the evolution of the capacitor [PSI], even with realistic rates of yeast sex | journal = PLOS Genetics | volume = 5 | issue = 6 | pages = e1000517 | date = June 2009 | pmid = 19521499 | pmc = 2686163 | doi = 10.1371/journal.pgen.1000517 | doi-access = free }}</ref> The existence of this possibility increases the [[evolvability]] of a species.

More than 100&nbsp;cases of [[transgenerational epigenetic inheritance]] phenomena have been reported in a wide range of organisms, including prokaryotes, plants, and animals.<ref name="Jablonka09">{{cite journal | vauthors = Jablonka E, Raz G | title = Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution | journal = The Quarterly Review of Biology | volume = 84 | issue = 2 | pages = 131–76 | date = June 2009 | pmid = 19606595 | doi = 10.1086/598822 | url = http://compgen.unc.edu/wiki/images/d/df/JablonkaQtrRevBio2009.pdf | citeseerx = 10.1.1.617.6333 | s2cid = 7233550 | access-date = 1 November 2017 | archive-date = 15 July 2011 | archive-url = https://web.archive.org/web/20110715111243/http://compgen.unc.edu/wiki/images/d/df/JablonkaQtrRevBio2009.pdf | url-status = dead }}</ref> For instance, [[Nymphalis antiopa|mourning-cloak butterflies]] will change color through hormone changes in response to experimentation of varying temperatures.<ref>Davies, Hazel (2008). Do Butterflies Bite?: Fascinating Answers to Questions about Butterflies and Moths (Animals Q&A). Rutgers University Press.</ref>

The filamentous fungus ''Neurospora crassa'' is a prominent model system for understanding the control and function of cytosine methylation. In this organism, DNA methylation is associated with relics of a genome-defense system called RIP (repeat-induced point mutation) and silences gene expression by inhibiting transcription elongation.<ref name="pmid19092133">{{cite journal | vauthors = Lewis ZA, Honda S, Khlafallah TK, Jeffress JK, Freitag M, Mohn F, Schübeler D, Selker EU | title = Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa | journal = Genome Research | volume = 19 | issue = 3 | pages = 427–37 | date = March 2009 | pmid = 19092133 | pmc = 2661801 | doi = 10.1101/gr.086231.108 }}</ref>

The [[yeast prion]] PSI is generated by a conformational change of a translation termination factor, which is then inherited by daughter cells. This can provide a survival advantage under adverse conditions, exemplifying epigenetic regulation which enables unicellular organisms to respond rapidly to environmental stress. Prions can be viewed as epigenetic agents capable of inducing a phenotypic change without modification of the genome.<ref name=JorgTost>{{cite book | vauthors = Tost J | title= Epigenetics | publisher= Caister Academic Press | location= Norfolk, England | year= 2008 | isbn= 978-1-904455-23-3 }}</ref>

Direct detection of epigenetic marks in microorganisms is possible with [[single molecule real time sequencing]], in which polymerase sensitivity allows for measuring methylation and other modifications as a DNA molecule is being sequenced.<ref>{{cite journal | vauthors = Schadt EE, Banerjee O, Fang G, Feng Z, Wong WH, Zhang X, Kislyuk A, Clark TA, Luong K, Keren-Paz A, Chess A, Kumar V, Chen-Plotkin A, Sondheimer N, Korlach J, Kasarskis A | title = Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases | journal = Genome Research | volume = 23 | issue = 1 | pages = 129–41 | date = January 2013 | pmid = 23093720 | pmc = 3530673 | doi = 10.1101/gr.136739.111 }}</ref> Several projects have demonstrated the ability to collect genome-wide epigenetic data in bacteria.<ref>{{cite journal | vauthors = Davis BM, Chao MC, Waldor MK | title = Entering the era of bacterial epigenomics with single molecule real time DNA sequencing | journal = Current Opinion in Microbiology | volume = 16 | issue = 2 | pages = 192–8 | date = April 2013 | pmid = 23434113 | pmc = 3646917 | doi = 10.1016/j.mib.2013.01.011 }}</ref><ref>{{cite journal | vauthors = Lluch-Senar M, Luong K, Lloréns-Rico V, Delgado J, Fang G, Spittle K, Clark TA, Schadt E, Turner SW, Korlach J, Serrano L | title = Comprehensive methylome characterization of Mycoplasma genitalium and Mycoplasma pneumoniae at single-base resolution | journal = PLOS Genetics | volume = 9 | issue = 1 | pages = e1003191 | year = 2013 | pmid = 23300489 | pmc = 3536716 | doi = 10.1371/journal.pgen.1003191 | veditors = Richardson PM | doi-access = free }}</ref><ref>{{cite journal | vauthors = Murray IA, Clark TA, Morgan RD, Boitano M, Anton BP, Luong K, Fomenkov A, Turner SW, Korlach J, Roberts RJ | title = The methylomes of six bacteria | journal = Nucleic Acids Research | volume = 40 | issue = 22 | pages = 11450–62 | date = December 2012 | pmid = 23034806 | pmc = 3526280 | doi = 10.1093/nar/gks891 }}</ref><ref>
{{cite journal | vauthors = Fang G, Munera D, Friedman DI, Mandlik A, Chao MC, Banerjee O, Feng Z, Losic B, Mahajan MC, Jabado OJ, Deikus G, Clark TA, Luong K, Murray IA, Davis BM, Keren-Paz A, Chess A, Roberts RJ, Korlach J, Turner SW, Kumar V, Waldor MK, Schadt EE | title = Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing | journal = Nature Biotechnology | volume = 30 | issue = 12 | pages = 1232–9 | date = December 2012 | pmid = 23138224 | pmc = 3879109 | doi = 10.1038/nbt.2432 }}
</ref>