Editing Genomic imprinting (section)

==Imprinted genes in mammals==
That imprinting might be a feature of mammalian development was suggested in breeding experiments in mice carrying reciprocal [[chromosomal translocation]]s.<ref name="Lyon and Glenister 1977">{{cite journal | vauthors = Lyon MF, Glenister PH | title = Factors affecting the observed number of young resulting from adjacent-2 disjunction in mice carrying a translocation | journal = Genetical Research | volume = 29 | issue = 1 | pages = 83–92 | date = February 1977 | pmid = 559611 | doi = 10.1017/S0016672300017134 | doi-access = free }}</ref> Nucleus transplantation experiments in [[mouse]] zygotes in the early 1980s confirmed that normal development requires the contribution of both the maternal and paternal genomes. The vast majority of mouse embryos derived from [[parthenogenesis]] (called parthenogenones, with two maternal or egg genomes) and [[androgenesis]] (called androgenones, with two paternal or sperm genomes) die at or before the blastocyst/implantation stage. In the rare instances that they develop to postimplantation stages, gynogenetic embryos show better embryonic development relative to placental development, while for androgenones, the reverse is true. Nevertheless, for the latter, only a few have been described (in a 1984 paper).<ref name="Barton 1984">{{cite journal | vauthors = Barton SC, Surani MA, Norris ML | title = Role of paternal and maternal genomes in mouse development | journal = Nature | volume = 311 | issue = 5984 | pages = 374–376 | year = 1984 | pmid = 6482961 | doi = 10.1038/311374a0 | bibcode = 1984Natur.311..374B | author-link2 = Azim Surani | s2cid = 4321070 }} {{closed access}}</ref><ref name="Mann and Lovell-Badge 1984">{{cite journal | vauthors = Mann JR, Lovell-Badge RH | title = Inviability of parthenogenones is determined by pronuclei, not egg cytoplasm | journal = Nature | volume = 310 | issue = 5972 | pages = 66–67 | year = 1984 | pmid = 6738704 | doi = 10.1038/310066a0 | bibcode = 1984Natur.310...66M | s2cid = 4336389 }}</ref><ref name="McGrath and Solter 1984">{{cite journal | vauthors = McGrath J, Solter D | title = Completion of mouse embryogenesis requires both the maternal and paternal genomes | journal = Cell | volume = 37 | issue = 1 | pages = 179–183 | date = May 1984 | pmid = 6722870 | doi = 10.1016/0092-8674(84)90313-1 | doi-access = free }}</ref> Nevertheless, in 2018 genome editing allowed for  bipaternal and viable bimaternal<ref>{{cite journal | vauthors = Sagi I, Bar S, Benvenisty N | title = Mice from Same-Sex Parents: CRISPRing Out the Barriers for Unisexual Reproduction | language = English | journal = Cell Stem Cell | volume = 23 | issue = 5 | pages = 625–627 | date = November 2018 | pmid = 30388415 | doi = 10.1016/j.stem.2018.10.012 | s2cid = 53252140 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Li ZK, Wang LY, Wang LB, Feng GH, Yuan XW, Liu C, Xu K, Li YH, Wan HF, Zhang Y, Li YF, Li X, Li W, Zhou Q, Hu BY | display-authors = 6 | title = Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions | language = English | journal = Cell Stem Cell | volume = 23 | issue = 5 | pages = 665–676.e4 | date = November 2018 | pmid = 30318303 | doi = 10.1016/j.stem.2018.09.004 | s2cid = 205251810 | doi-access = free }}</ref> mouse and even (in 2022) parthenogenesis, still this is far from full reimprinting.<ref>{{cite journal | vauthors = Wei Y, Yang CR, Zhao ZA | title = Viable offspring derived from single unfertilized mammalian oocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 119 | issue = 12 | pages = e2115248119 | date = March 2022 | pmid = 35254875 | pmc = 8944925 | doi = 10.1073/pnas.2115248119 | doi-access = free | bibcode = 2022PNAS..11915248W }}</ref> Finally in March 2023 viable bipaternal embryos were created.<ref>{{Cite journal |last1=Ledford |first1=Heidi |last2=Kozlov |first2=Max |date=2023-03-09 |title=The mice with two dads: scientists create eggs from male cells |url=https://www.nature.com/articles/d41586-023-00717-7 |journal=Nature |volume=615 |issue=7952 |pages=379–380 |language=en |doi=10.1038/d41586-023-00717-7|pmid=36894725 |bibcode=2023Natur.615..379L |s2cid=257428648 |url-access=subscription }}</ref>

No naturally occurring cases of parthenogenesis exist in mammals because of imprinted genes. However, in 2004, experimental manipulation by Japanese researchers of a paternal methylation imprint controlling the ''[[Insulin-like growth factor 2|Igf2]]'' gene led to the birth of a mouse (named [[Kaguya (mouse)|Kaguya]]) with two maternal sets of chromosomes, though it is not a true parthenogenone since cells from two different female mice were used. The researchers were able to succeed by using one egg from an immature parent, thus reducing maternal imprinting, and modifying it to express the gene Igf2, which is normally only expressed by the paternal copy of the gene.

Parthenogenetic/gynogenetic embryos have twice the normal expression level of maternally derived genes, and lack expression of paternally expressed genes, while the reverse is true for androgenetic embryos. It is now known that there are at least 80 imprinted genes in humans and mice, many of which are involved in embryonic and placental growth and development.<ref name="Wood and Oakey 2006">{{cite journal | vauthors = Wood AJ, Oakey RJ | title = Genomic imprinting in mammals: emerging themes and established theories | journal = PLOS Genetics | volume = 2 | issue = 11 | pages = e147 | date = November 2006 | pmid = 17121465 | pmc = 1657038 | doi = 10.1371/journal.pgen.0020147 | doi-access = free }}</ref><ref name="Isles and Holland 2005">{{cite journal | vauthors = Isles AR, Holland AJ | title = Imprinted genes and mother-offspring interactions | journal = Early Human Development | volume = 81 | issue = 1 | pages = 73–77 | date = January 2005 | pmid = 15707717 | doi = 10.1016/j.earlhumdev.2004.10.006 }}</ref><ref name="Morison 2005">{{cite journal | vauthors = Morison IM, Ramsay JP, Spencer HG | title = A census of mammalian imprinting | journal = Trends in Genetics | volume = 21 | issue = 8 | pages = 457–465 | date = August 2005 | pmid = 15990197 | doi = 10.1016/j.tig.2005.06.008 }}</ref><ref name="Reik and Lewis 2005">{{cite journal | author1 = Reik W |author-link1 =Wolf Reik| author2 = Lewis A | title = Co-evolution of X-chromosome inactivation and imprinting in mammals | journal = Nature Reviews. Genetics | volume = 6 | issue = 5 | pages = 403–410 | date = May 2005 | pmid = 15818385 | doi = 10.1038/nrg1602 | s2cid = 21091004 }}</ref> [[Hybrid (biology)|Hybrid]] offspring of two species may exhibit unusual growth due to the novel combination of imprinted genes.<ref>{{Cite news |date=2000-04-30 |title=Gene Tug-of-War Leads to Distinct Species |publisher=[[Howard Hughes Medical Institute]] |url=http://www.hhmi.org/news/tilghman.html |access-date=2008-07-02 |archive-date=2013-03-28 |archive-url=https://web.archive.org/web/20130328144948/http://www.hhmi.org/news/tilghman.html |url-status=dead }}</ref>

Various methods have been used to identify imprinted genes. In swine, Bischoff ''et al.'' compared transcriptional profiles using [[DNA microarray]]s to survey differentially expressed genes between parthenotes (2 maternal genomes) and control fetuses (1 maternal, 1 paternal genome).<ref>{{cite journal | vauthors = Bischoff SR, Tsai S, Hardison N, Motsinger-Reif AA, Freking BA, Nonneman D, Rohrer G, Piedrahita JA | display-authors = 6 | title = Characterization of conserved and nonconserved imprinted genes in swine | journal = Biology of Reproduction | volume = 81 | issue = 5 | pages = 906–920 | date = November 2009 | pmid = 19571260 | pmc = 2770020 | doi = 10.1095/biolreprod.109.078139 }}</ref> An intriguing study surveying the [[transcriptome]] of [[murine]] brain tissues revealed over 1300 imprinted gene loci (approximately 10-fold more than previously reported) by RNA-sequencing from F1 hybrids resulting from reciprocal crosses.<ref>{{cite journal | vauthors = Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C | title = High-resolution analysis of parent-of-origin allelic expression in the mouse brain | journal = Science | volume = 329 | issue = 5992 | pages = 643–648 | date = August 2010 | pmid = 20616232 | pmc = 3005244 | doi = 10.1126/science.1190830 | bibcode = 2010Sci...329..643G }}</ref> The result however has been challenged by others who claimed that this is an overestimation by an order of magnitude due to flawed statistical analysis.<ref>{{cite journal | vauthors = Hayden EC | title = RNA studies under fire | journal = Nature | volume = 484 | issue = 7395 | pages = 428 | date = April 2012 | pmid = 22538578 | doi = 10.1038/484428a | bibcode = 2012Natur.484..428C | doi-access = free }}</ref><ref>{{cite journal | vauthors = DeVeale B, van der Kooy D, Babak T | title = Critical evaluation of imprinted gene expression by RNA-Seq: a new perspective | journal = PLOS Genetics | volume = 8 | issue = 3 | pages = e1002600 | year = 2012 | pmid = 22479196 | pmc = 3315459 | doi = 10.1371/journal.pgen.1002600 | doi-access = free }}</ref>

In domesticated livestock, [[single-nucleotide polymorphism]]s in imprinted genes influencing [[foetal]] growth and development have been shown to be associated with economically important production traits in cattle, sheep and pigs.<ref name="ReferenceB">{{cite journal | vauthors = Magee DA, Spillane C, Berkowicz EW, Sikora KM, MacHugh DE | title = Imprinted loci in domestic livestock species as epigenomic targets for artificial selection of complex traits | journal = Animal Genetics | volume = 45 | issue = Suppl 1 | pages = 25–39 | date = August 2014 | pmid = 24990393 | doi = 10.1111/age.12168 }}</ref><ref>{{cite journal | vauthors = Magee DA, Sikora KM, Berkowicz EW, Berry DP, Howard DJ, Mullen MP, Evans RD, Spillane C, MacHugh DE | display-authors = 6 | title = DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle | journal = BMC Genetics | volume = 11 | pages = 93 | date = October 2010 | pmid = 20942903 | pmc = 2965127 | doi = 10.1186/1471-2156-11-93 | doi-access = free }}</ref>

===Genetic mapping of imprinted genes===
At the same time as the generation of the gynogenetic and androgenetic embryos discussed above, mouse embryos were also being generated that contained only small regions that were derived from either a paternal or maternal source.<ref name="Cattanach and Kirk 1985">{{cite journal | vauthors = Cattanach BM, Kirk M | title = Differential activity of maternally and paternally derived chromosome regions in mice | journal = Nature | volume = 315 | issue = 6019 | pages = 496–498 | year = 1985 | pmid = 4000278 | doi = 10.1038/315496a0 | bibcode = 1985Natur.315..496C | s2cid = 4337753 }}</ref><ref name="McLaughlin 1996">{{cite journal | vauthors = McLaughlin KJ, Szabó P, Haegel H, Mann JR | title = Mouse embryos with paternal duplication of an imprinted chromosome 7 region die at midgestation and lack placental spongiotrophoblast | journal = Development | volume = 122 | issue = 1 | pages = 265–270 | date = January 1996 | pmid = 8565838 | doi = 10.1242/dev.122.1.265 }}</ref> The generation of a series of such [[uniparental disomy|uniparental disomies]], which together span the entire genome, allowed the creation of an imprinting map.<ref>{{Cite web |year=2008 |title=Mouse Imprinting Data and References |url=http://www.har.mrc.ac.uk/research/genomic_imprinting/ |url-status=dead |archive-url=https://web.archive.org/web/20120703103129/http://har.mrc.ac.uk/research/genomic_imprinting/ |archive-date=2012-07-03 |access-date=2008-07-02 |publisher=MRC Harwell |vauthors=Beechey C, Cattanach BM, Lake A, Peters J}}</ref> Those regions which when inherited from a single parent result in a discernible phenotype contain imprinted gene(s). Further research showed that within these regions there were often numerous imprinted genes.<ref name="Bartolomei and Tilghman 1997">{{cite journal | vauthors = Bartolomei MS, Tilghman SM | title = Genomic imprinting in mammals | journal = Annual Review of Genetics | volume = 31 | pages = 493–525 | year = 1997 | pmid = 9442905 | pmc = 3941233 | doi = 10.1146/annurev.genet.31.1.493 }}</ref> Around 80% of imprinted genes are found in clusters such as these, called imprinted domains, suggesting a level of co-ordinated control.<ref name="Reik and Walter 2001">{{cite journal | author1 = Reik W |author-link1 =Wolf Reik | author2=Walter J | title = Genomic imprinting: parental influence on the genome | journal = Nature Reviews. Genetics | volume = 2 | issue = 1 | pages = 21–32 | date = January 2001 | pmid = 11253064 | doi = 10.1038/35047554 | s2cid = 12050251 }}</ref> More recently, genome-wide screens to identify imprinted genes have used differential expression of mRNAs from control fetuses and parthenogenetic or androgenetic fetuses hybridized to [[gene expression profiling]] microarrays,<ref>{{cite journal | vauthors = Kobayashi H, Yamada K, Morita S, Hiura H, Fukuda A, Kagami M, Ogata T, Hata K, Sotomaru Y, Kono T | display-authors = 6 | title = Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2 | journal = Genomics | volume = 93 | issue = 5 | pages = 461–472 | date = May 2009 | pmid = 19200453 | doi = 10.1016/j.ygeno.2008.12.012 | doi-access = free }}</ref> allele-specific gene expression using [[SNP genotyping]] microarrays,<ref>{{cite journal | vauthors = Bjornsson HT, Albert TJ, Ladd-Acosta CM, Green RD, Rongione MA, Middle CM, Irizarry RA, Broman KW, Feinberg AP | display-authors = 6 | title = SNP-specific array-based allele-specific expression analysis | journal = Genome Research | volume = 18 | issue = 5 | pages = 771–779 | date = May 2008 | pmid = 18369178 | pmc = 2336807 | doi = 10.1101/gr.073254.107 }}</ref> transcriptome sequencing,<ref>{{cite journal | vauthors = Babak T, Deveale B, Armour C, Raymond C, Cleary MA, van der Kooy D, Johnson JM, Lim LP | display-authors = 6 | title = Global survey of genomic imprinting by transcriptome sequencing | journal = Current Biology | volume = 18 | issue = 22 | pages = 1735–1741 | date = November 2008 | pmid = 19026546 | doi = 10.1016/j.cub.2008.09.044 | s2cid = 10143690 | doi-access = free | bibcode = 2008CBio...18.1735B }}</ref> and in silico prediction pipelines.<ref>{{cite journal | vauthors = Luedi PP, Dietrich FS, Weidman JR, Bosko JM, Jirtle RL, Hartemink AJ | title = Computational and experimental identification of novel human imprinted genes | journal = Genome Research | volume = 17 | issue = 12 | pages = 1723–1730 | date = December 2007 | pmid = 18055845 | pmc = 2099581 | doi = 10.1101/gr.6584707 }}</ref>

===Imprinting mechanisms===
Imprinting is a dynamic process. It must be possible to erase and re-establish imprints through each generation so that genes that are imprinted in an adult may still be expressed in that adult's offspring. (For example, the maternal genes that control insulin production will be imprinted in a male but will be expressed in any of the male's offspring that inherit these genes.) The nature of imprinting must therefore be [[epigenetics|epigenetic]] rather than DNA sequence dependent. In [[germline]] cells the imprint is erased and then re-established according to the [[sex]] of the individual, i.e. in the developing sperm (during [[spermatogenesis]]), a paternal imprint is established, whereas in developing oocytes ([[oogenesis]]), a maternal imprint is established. This process of erasure and [[reprogramming]]<ref>{{cite journal |author1 = Reik W |author-link1 =Wolf Reik |author2 = Dean W|author3 = Walter J | title = Epigenetic reprogramming in mammalian development | journal = Science | volume = 293 | issue = 5532 | pages = 1089–1093 | date = August 2001 | pmid = 11498579 | doi = 10.1126/science.1063443 | s2cid = 17089710 }}</ref> is necessary such that the germ cell imprinting status is relevant to the sex of the individual. In both plants and mammals there are two major mechanisms that are involved in establishing the imprint; these are [[DNA methylation]] and [[histone]] modifications.

Recently, a new study<ref name="Court and Tayama 2014">{{cite journal | vauthors = Court F, Tayama C, Romanelli V, Martin-Trujillo A, Iglesias-Platas I, Okamura K, Sugahara N, Simón C, Moore H, Harness JV, Keirstead H, Sanchez-Mut JV, Kaneki E, Lapunzina P, Soejima H, Wake N, Esteller M, Ogata T, Hata K, Nakabayashi K, Monk D | display-authors = 6 | title = Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment | journal = Genome Research | volume = 24 | issue = 4 | pages = 554–569 | date = April 2014 | pmid = 24402520 | pmc = 3975056 | doi = 10.1101/gr.164913.113 }}</ref> has suggested a novel inheritable imprinting mechanism in humans that would be specific of [[placenta]]l tissue and that is independent of DNA methylation (the main and classical mechanism for genomic imprinting). This was observed in humans, but not in mice, suggesting development after the evolutionary divergence of humans and mice, ~80 [[Mya (unit)|Mya]]. Among the hypothetical explanations for this novel phenomenon, two possible mechanisms have been proposed: either a histone modification that confers imprinting at novel placental-specific imprinted ''loci'' or, alternatively, a recruitment of [[DNA methyltransferase|DNMTs]] to these loci by a specific and unknown [[transcription factor]] that would be expressed during early trophoblast differentiation.

===Regulation===
The grouping of imprinted genes within clusters allows them to share common regulatory elements, such as [[non-coding RNA]]s and [[differentially methylated regions (DMRs)]]. When these regulatory elements control the imprinting of one or more genes, they are known as imprinting control regions (ICR). The expression of [[non-coding RNA]]s, such as [[antisense RNA|antisense Igf2r RNA]] (''Air'') on mouse chromosome 17 and [[KCNQ1OT1]] on human chromosome 11p15.5, have been shown to be essential for the imprinting of genes in their corresponding regions.<ref>{{cite journal | vauthors = Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM | title = Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes | journal = Genes & Development | volume = 20 | issue = 10 | pages = 1268–1282 | date = May 2006 | pmid = 16702402 | pmc = 1472902 | doi = 10.1101/gad.1416906 }}</ref>

Differentially methylated regions are generally segments of DNA rich in [[cytosine]] and [[guanine]] nucleotides, with the cytosine nucleotides methylated on one copy but not on the other. Contrary to expectation, methylation does not necessarily mean silencing; instead, the effect of methylation depends upon the default state of the region.<ref>{{cite journal | vauthors = Jin B, Li Y, Robertson KD | title = DNA methylation: superior or subordinate in the epigenetic hierarchy? | journal = Genes & Cancer | volume = 2 | issue = 6 | pages = 607–617 | date = June 2011 | pmid = 21941617 | pmc = 3174260 | doi = 10.1177/1947601910393957 }}</ref>

===Functions of imprinted genes===
The control of expression of specific genes by genomic imprinting is unique to [[theria]]n mammals ([[eutherians|placental mammals]] and [[marsupials]]) and flowering plants. Imprinting of whole chromosomes has been reported in mealybugs (Genus: ''[[Pseudococcus]]'')<ref name="Schrader 1921" /><ref name="Brown and Nur 1964" /><ref name="Hughes-Schrader 1948" /><ref name="Nur 1990" /> and a [[fungus gnat]] (''Sciara'').<ref name="Metz 1938">{{Cite journal |vauthors=Metz CW |year=1938 |title=Chromosome behavior, inheritance and sex determination in ''Sciara'' |journal=[[American Naturalist]] |volume=72 |issue=743 |pages=485–520 |doi=10.1086/280803 |jstor=2457532 |s2cid=83550755}}</ref> It has also been established that [[X-chromosome]] inactivation occurs in an imprinted manner in the extra-embryonic tissues of mice and all tissues in marsupials, where it is always the paternal X-chromosome which is silenced.<ref name="Reik and Walter 2001" /><ref name="Alleman and Doctor 2000">{{cite journal | vauthors = Alleman M, Doctor J | title = Genomic imprinting in plants: observations and evolutionary implications | journal = Plant Molecular Biology | volume = 43 | issue = 2–3 | pages = 147–161 | date = June 2000 | pmid = 10999401 | doi = 10.1023/A:1006419025155 | s2cid = 9499846 }}</ref>

The majority of imprinted genes in mammals have been found to have roles in the control of embryonic growth and development, including development of the placenta.<ref name="Isles and Holland 2005" /><ref name="Tycko and Morison 2002">{{cite journal | vauthors = Tycko B, Morison IM | title = Physiological functions of imprinted genes | journal = Journal of Cellular Physiology | volume = 192 | issue = 3 | pages = 245–258 | date = September 2002 | pmid = 12124770 | doi = 10.1002/jcp.10129 | s2cid = 42971427 | doi-access = free }}</ref> Other imprinted genes are involved in post-natal development, with roles affecting suckling and metabolism.<ref name="Tycko and Morison 2002" /><ref name="Constancia 2004">{{cite journal | author1 =Constância M| author2 = Pickard B| author3 = Kelsey G | author4 = Reik W |author-link4 =Wolf Reik | title = Imprinting mechanisms | journal = Genome Research | volume = 8 | issue = 9 | pages = 881–900 | date = September 1998 | pmid = 9750189 | doi = 10.1101/gr.8.9.881 | doi-access = free }}</ref>

===Hypotheses on the origins of imprinting===
A widely accepted hypothesis for the evolution of genomic imprinting is the "parental conflict hypothesis".<ref name="Moore and Haig 1991">{{cite journal | vauthors = Moore T, Haig D | title = Genomic imprinting in mammalian development: a parental tug-of-war | journal = Trends in Genetics | volume = 7 | issue = 2 | pages = 45–49 | date = February 1991 | pmid = 2035190 | doi = 10.1016/0168-9525(91)90230-N }}</ref> Also known as the kinship theory of genomic imprinting, this hypothesis states that the inequality between parental genomes due to imprinting is a result of the [[sexual conflict|differing interests of each parent]] in terms of the [[fitness (biology)|evolutionary fitness of their genes]].<ref name="Haig 1997">{{cite journal | vauthors = Haig D | title = Parental antagonism, relatedness asymmetries, and genomic imprinting | journal = Proceedings. Biological Sciences | volume = 264 | issue = 1388 | pages = 1657–1662 | date = November 1997 | pmid = 9404029 | pmc = 1688715 | doi = 10.1098/rspb.1997.0230 | bibcode = 1997RSPSB.264.1657H | author-link = David Haig (biologist) }}</ref><ref name="Haig 2000">{{Cite journal |vauthors=Haig D |year=2000 |title=The kinship theory of genomic imprinting |journal=Annual Review of Ecology and Systematics |volume=31 |issue=1 |pages=9–32 |doi=10.1146/annurev.ecolsys.31.1.9|bibcode=2000AnRES..31....9H }}</ref> The [[father]]'s genes that encode for imprinting gain greater fitness through the success of the offspring, at the expense of the [[mother]]. The mother's evolutionary imperative is often to conserve resources for her own survival while providing sufficient nourishment to current and subsequent litters. Accordingly, paternally expressed genes tend to be growth-promoting whereas maternally expressed genes tend to be growth-limiting.<ref name="Moore and Haig 1991" /> In support of this hypothesis, genomic imprinting has been found in all placental mammals, where post-fertilisation offspring resource consumption at the expense of the mother is high; although it has also been found in [[oviparous]] birds<ref>{{cite journal | vauthors = McElroy JP, Kim JJ, Harry DE, Brown SR, Dekkers JC, Lamont SJ | title = Identification of trait loci affecting white meat percentage and other growth and carcass traits in commercial broiler chickens | journal = Poultry Science | volume = 85 | issue = 4 | pages = 593–605 | date = April 2006 | pmid = 16615342 | doi = 10.1093/ps/85.4.593 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tuiskula-Haavisto M, Vilkki J | title = Parent-of-origin specific QTL--a possibility towards understanding reciprocal effects in chicken and the origin of imprinting | journal = Cytogenetic and Genome Research | volume = 117 | issue = 1–4 | pages = 305–312 | year = 2007 | pmid = 17675872 | doi = 10.1159/000103192 | s2cid = 27834663 }}</ref> where there is relatively little post-fertilisation resource transfer and therefore less parental conflict. A small number of imprinted genes are fast evolving under positive Darwinian selection possibly due to antagonistic co-evolution.<ref name="O'Connell_2010">{{cite journal | vauthors = O'Connell MJ, Loughran NB, Walsh TA, Donoghue MT, Schmid KJ, Spillane C | title = A phylogenetic approach to test for evidence of parental conflict or gene duplications associated with protein-encoding imprinted orthologous genes in placental mammals | journal = Mammalian Genome | volume = 21 | issue = 9–10 | pages = 486–498 | date = October 2010 | pmid = 20931201 | doi = 10.1007/s00335-010-9283-5 | s2cid = 6883377 }}</ref> The majority of imprinted genes display high levels of micro-[[synteny]] conservation and have undergone very few duplications in placental mammalian lineages.<ref name="O'Connell_2010" />

However, our understanding of the molecular mechanisms behind genomic imprinting show that it is the maternal genome that controls much of the imprinting of both its own and the paternally-derived genes in the zygote, making it difficult to explain why the maternal genes would willingly relinquish their dominance to that of the paternally-derived genes in light of the conflict hypothesis.<ref name="Keverne">{{cite journal | vauthors = Keverne EB, Curley JP | title = Epigenetics, brain evolution and behaviour | journal = Frontiers in Neuroendocrinology | volume = 29 | issue = 3 | pages = 398–412 | date = June 2008 | pmid = 18439660 | doi = 10.1016/j.yfrne.2008.03.001 | url = http://champagnelab.psych.columbia.edu/docs/frontiers.pdf | url-status = dead | access-date = 2011-01-06 | s2cid = 10697086 | archive-url = https://web.archive.org/web/20100622154417/http://champagnelab.psych.columbia.edu/docs/frontiers.pdf | archive-date = 2010-06-22 }}</ref>

Another hypothesis proposed is that some imprinted genes act coadaptively to improve both fetal development and maternal provisioning for nutrition and care.<ref name="Peters2014" /><ref name="Keverne" /><ref>{{cite journal | vauthors = Wolf JB | title = Cytonuclear interactions can favor the evolution of genomic imprinting | journal = Evolution; International Journal of Organic Evolution | volume = 63 | issue = 5 | pages = 1364–1371 | date = May 2009 | pmid = 19425202 | doi = 10.1111/j.1558-5646.2009.00632.x | s2cid = 29251471 }}</ref> In it, a subset of paternally expressed genes are co-expressed in both the placenta and the mother's hypothalamus. This would come about through selective pressure from parent-infant coadaptation to improve infant survival. Paternally expressed 3 (''[[PEG3]]'') is a gene for which this hypothesis may apply.<ref name="Peters2014" />

Others have approached their study of the origins of genomic imprinting from a different side, arguing that [[natural selection]] is operating on the role of epigenetic marks as machinery for homologous chromosome recognition during meiosis, rather than on their role in differential expression.<ref name="de Villena et al 2000">{{cite journal | vauthors = Pardo-Manuel de Villena F, de la Casa-Esperón E, Sapienza C | title = Natural selection and the function of genome imprinting: beyond the silenced minority | journal = Trends in Genetics | volume = 16 | issue = 12 | pages = 573–579 | date = December 2000 | pmid = 11102708 | doi = 10.1016/S0168-9525(00)02134-X }}</ref> This argument centers on the existence of epigenetic effects on chromosomes that do not directly affect gene expression, but do depend on which parent the chromosome originated from.<ref name="de la Casa-Esperon 2003">{{cite journal | vauthors = de la Casa-Esperón E, Sapienza C | title = Natural selection and the evolution of genome imprinting | journal = Annual Review of Genetics | volume = 37 | pages = 349–370 | year = 2003 | pmid = 14616065 | doi = 10.1146/annurev.genet.37.110801.143741 }}</ref> This group of epigenetic changes that depend on the chromosome's parent of origin (including both those that affect gene expression and those that do not) are called parental origin effects, and include phenomena such as paternal [[X inactivation]] in the [[marsupial]]s, nonrandom parental [[chromatid]] distribution in the ferns, and even mating type switching in yeast.<ref name="de la Casa-Esperon 2003" /> This diversity in organisms that show parental origin effects has prompted theorists to place the evolutionary origin of genomic imprinting before the last common ancestor of plants and animals, over a billion years ago.<ref name="de Villena et al 2000" />

Natural selection for genomic imprinting requires genetic variation in a population. A hypothesis for the origin of this genetic variation states that the host-defense system responsible for silencing foreign DNA elements, such as genes of viral origin, mistakenly silenced genes whose silencing turned out to be beneficial for the organism.<ref>{{cite journal | vauthors = Barlow DP | title = Methylation and imprinting: from host defense to gene regulation? | journal = Science | volume = 260 | issue = 5106 | pages = 309–310 | date = April 1993 | pmid = 8469984 | doi = 10.1126/science.8469984 | bibcode = 1993Sci...260..309B | s2cid = 6925971 }}</ref> There appears to be an over-representation of [[retrotransposon|retrotransposed genes]], that is to say genes that are inserted into the genome by [[virus]]es, among imprinted genes. It has also been postulated that if the retrotransposed gene is inserted close to another imprinted gene, it may just acquire this imprint.<ref name="Chai 2001">{{cite journal | vauthors = Chai JH, Locke DP, Ohta T, Greally JM, Nicholls RD | title = Retrotransposed genes such as Frat3 in the mouse Chromosome 7C Prader-Willi syndrome region acquire the imprinted status of their insertion site | journal = Mammalian Genome | volume = 12 | issue = 11 | pages = 813–821 | date = November 2001 | pmid = 11845283 | doi = 10.1007/s00335-001-2083-1 | s2cid = 13419814 }}</ref>