Editing Chimera (genetics) (section)

==Types==

===Animals===

As the organism develops, it can come to possess [[organ (anatomy)|organ]]s that have different sets of [[chromosome]]s. For example, the chimera may have a [[liver]] composed of cells with one set of chromosomes and have a [[kidney]] composed of cells with a second set of chromosomes. This has occurred in humans, and at one time was thought to be extremely rare although more recent evidence suggests that this is not the case.<ref name="Norton" /><ref>Boklage, C.E. How New Humans Are Made. Hackensack, NJ; London: World Scientific Publishing Co. Pte. Ltd; 2010</ref>

This is particularly true for the [[marmoset]]. Recent research shows most marmosets are chimeras, sharing DNA with their [[fraternal twin]]s.<ref name="Ross2007" /> 95% of marmoset fraternal twins trade blood through [[chorionic]] fusions, making them [[hematopoietic]] chimeras.<ref name="Masahito Tachibana, Michelle Sparman and Shoukhrat Mitalipov" /><ref>{{cite journal | first1=N.| last1=Gengozian| last2=Batson| first2=JS| first3=P.| last3=Eide| title=Hematologic and Cytogenetic Evidence for Hematopoietic Chimerism in the Marmoset, Tamarinus Nigricollis| journal=Cytogenetics| year=1964| volume=10| issue=6| pages=384–393| doi=10.1159/000129828| pmid=14267132}}</ref>

In the [[budgerigar]], due to the many existing [[budgerigar colour genetics|plumage colour variations]], tetragametic chimeras can be very conspicuous, as the resulting bird will have an obvious split between two colour types{{snd}} often divided bilaterally down the centre. These individuals are known as [[half-sider budgerigar]]s.<ref name="guardian">{{cite news |last1=GrrlScientist |title=Half-siders: A tale of two birdies |url=https://www.theguardian.com/science/grrlscientist/2014/jan/31/grrlscientist-halfsider-chimera-bilateral-gynandromorph-birds |website=The Guardian |access-date=30 July 2023}}</ref>

An animal chimera is a single [[organism]] that is composed of two or more different populations of genetically distinct [[cell (biology)|cells]] that originated from different [[zygote]]s involved in [[sexual reproduction]]. If the different cells have emerged from the same zygote, the organism is called a [[Mosaic (genetics)|mosaic]]. Innate chimeras are formed from at least four parent cells (two fertilised eggs or early embryos fused together). Each population of cells keeps its own character and the resulting organism is a mixture of tissues. Cases of [[human chimera]]s have been documented.<ref name="Norton" />

====Chimerism in humans====
{{Main|Human chimera}}Some consider [[Mosaic (genetics)|mosaicism]] to be a form of chimerism,<ref>{{Cite web |title=Chimaera - an overview |website=ScienceDirect |url=https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/chimaera |access-date=2024-01-20 |quote=Another form of chimera is the mosaic, which is a composite individual derived from a single fertilized egg.}}</ref> while others consider them to be distinct.<ref>{{Cite journal |last=Madan |first=Kamlesh |date=2020-09-01 |title=Natural human chimeras: A review |journal=European Journal of Medical Genetics |volume=63 |issue=9 |pages=103971 |doi=10.1016/j.ejmg.2020.103971 |issn=1769-7212 |quote=A chimera is an organism whose cells are derived from two or more zygotes as opposed to a mosaic whose different cell lines are derived from a single zygote|doi-access=free |pmid=32565253 }}</ref><ref>{{Cite journal |last1=Anderson |first1=D. |last2=Billingham |first2=R. E. |last3=Lampkin |first3=G. H. |last4=Medawar |first4=P. B. |date=1951-12-01 |title=The use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle |url=https://www.nature.com/articles/hdy195138 |journal=Heredity |language=en |volume=5 |issue=3 |pages=379–397 |doi=10.1038/hdy.1951.38 |issn=1365-2540 |quote=In the current embryological (which is also the classical) sense, a 'chimaera' is an organism whose cells derive from two or more distinct zygote lineages, and this is the sense which the term 'genetical chimaera' is here intended to convey. 'Genetical mosaic' is less suitable, because a mosaic is formed of the cells of a single zygote lineage.}}</ref><ref name=":0">{{Cite journal |last=Santelices |first=B. |date=2004-11-01 |title=Mosaicism and chimerism as components of intraorganismal genetic heterogeneity |url=https://academic.oup.com/jeb/article/17/6/1187/7323396 |journal=Journal of Evolutionary Biology |language=en |volume=17 |issue=6 |pages=1187–1188 |doi=10.1111/j.1420-9101.2004.00813.x |pmid=15525401 |issn=1010-061X |quote=Mosaicism originates by intrinsic genetic variations caused, among other processes, by somatic mutations, while chimerism originates from allogenic fusion or grafting. As such, chimerism is much rarer and involves a much larger genetic change than mosaicism.}}</ref> Mosaicism involves a [[mutation]] of the genetic material in a cell, giving rise to a subset of cells that are different from the rest. Natural chimerism is the fusion of more than one fertilized [[zygote]] in the early stages of [[prenatal development]]. It is much rarer than mosaicism.<ref name=":0" />

In artificial chimerism, an individual has one [[cell lineage]] that was inherited genetically at the time of the formation of the human embryo and the other that was introduced through a procedure, including [[organ transplantation]] or [[blood transfusion]].<ref>{{Cite journal |last=Rinkevich |first=B. |date=June 2001 |title=Human natural chimerism: an acquired character or a vestige of evolution? |journal=Human Immunology |volume=62 |issue=6 |pages=651–657 |doi=10.1016/s0198-8859(01)00249-x |issn=0198-8859 |pmid=11390041}}</ref> Specific types of transplants that could induce this condition include bone marrow transplants and organ transplants, as the recipient's body essentially works to permanently incorporate the new blood stem cells into it.

Boklage argues that many human 'mosaic' cell lines will be "found to be chimeric if properly tested".<ref>{{Cite journal |last=Boklage |first=Charles E. |date=2006 |title=Embryogenesis of chimeras, twins and anterior midline asymmetries |url=https://academic.oup.com/humrep/article/21/3/579/770117 |journal=Human Reproduction |volume=21 |issue=3 |pages=579–591 |doi=10.1093/humrep/dei370 |doi-access=free|pmid=16253966 }}</ref>

In contrast, a human where each cell contains genetic material from two organisms of different breeds, varieties, species or genera is called a [[human–animal hybrid]].<ref>{{cite web |url=https://embryo.asu.edu/pages/hybrids-and-chimeras-consultation-ethical-and-social-implications-creating-humananimal-embryos |title='Hybrids and Chimeras: A Consultation on the Ethical and Social Implications of Creating Human/Animal Embryos in Research' (2007), by the HFEA |website=The Embryo Project at Arizona State University |first1=Sarah |last1=Taddeo |first2=Jason S. |last2=Robert |date=2014-11-04}}</ref>

While German [[dermatologist]] [[Alfred Blaschko]] described [[Blaschko's lines]] in 1901, the genetic science took until the 1930s to approach a vocabulary for the phenomenon. The term ''genetic chimera'' has been used at least since the 1944 article of Belgovskii.<ref name="belgovskii44">{{cite book |last1=Belgovskii |first1=M. L. |title=OTS 61-11476 |date=1944 |publisher=United States Department of Commerce Office of Technical Services |chapter=The Causes of Mosaicism Associated With Heterochromatic Chromosome Regions}}</ref>

This condition is either innate or it is synthetic, acquired for example through the infusion of [[allogeneic]] [[blood cell]]s during [[Organ transplant|transplantation]] or [[Blood transfusion|transfusion]].{{citation needed|date=February 2021}}

In nonidentical twins, innate chimerism occurs by means of blood vessel [[anastomose]]s. The likelihood of offspring being a chimera is increased if it is created via [[in vitro fertilization|in vitro fertilisation]].<ref name="Strain" /> Chimeras can often breed, but the fertility and type of offspring depend on which cell line gave rise to the ovaries or testes; varying degrees of [[intersex]] differences may result if one set of cells is genetically female and another genetically male.{{citation needed|date=February 2021}}

On January 22, 2019, the [[National Society of Genetic Counselors]] released an article ''Chimerism Explained: How One Person Can Unknowingly Have Two Sets of DNA'', where they state, "where a twin pregnancy evolves into one child, is currently believed to be one of the rarer forms. However, we know that 20 to 30% of singleton pregnancies were originally a twin or a multiple pregnancy".<ref>{{Cite web|url=https://www.nsgc.org/p/bl/et/blogaid=1084|title=Chimerism Explained: How One Person Can Unknowingly Have Two Sets of DNA|website=National Society of Genetic Counselors|access-date=2020-02-02|archive-date=2020-02-02 |archive-url=https://web.archive.org/web/20200202124939/https://www.nsgc.org/p/bl/et/blogaid%3D1084|url-status=dead}}</ref>

Most human chimeras will go through life without realizing they are chimeras. The difference in phenotypes may be subtle (e.g., having a [[hitchhiker's thumb]] and a straight thumb, eyes of slightly different colors, differential hair growth on opposite sides of the body, etc.) or completely undetectable. Chimeras may also show, under a certain spectrum of UV light, distinctive marks on the back resembling that of arrow points pointing downward from the shoulders down to the lower back; this is one expression of pigment unevenness called [[Blaschko's lines]].<ref>{{cite web |url=http://www.thetech.org/genetics/ask.php?id=75 |title=Understanding Genetics: Human Health and the Genome |date=November 30, 2004 |work=Ask a Geneticist |publisher=[[Stanford University School of Medicine]] |first1=Barry |last1=Starr |archive-url=https://web.archive.org/web/20110724035334/http://www.thetech.org/genetics/ask.php?id=75 |archive-date=2011-07-24}}<!-- Date determined from list at https://web.archive.org/web/20110805030220/http://www.thetech.org/genetics/asklist.php?category=% --></ref>

{{anchor|(KarenKeegan)}}Another case was that of Karen Keegan, who was also suspected (initially) of not being her children's biological mother, after DNA tests on her adult sons for a kidney transplant she needed seemed to show that she was not their mother.<ref name="Norton" /><ref>{{cite episode |url=http://www.five.tv/programmes/extraordinarypeople/twininside/ |title=The Twin Inside Me: Extraordinary People |series=Extraordinary People |station=[[Five (TV channel)|Channel 5]] (UK) |date=9 March 2006 |archive-url=https://web.archive.org/web/20060526105634/http://www.five.tv/programmes/extraordinarypeople/twininside/ |archive-date=May 26, 2006 |url-status=dead}}</ref>

===Plants===
[[File:Starr-080117-1519-Pelargonium x hortorum-variegated leaves-Walmart Kahului-Maui (24873763676).jpg|right|thumb|upright|The green cells in the centres of the leaves of this ''[[Pelargonium]]'' plant have formed from the epithelium cell layer, which has normal chlorophyll. That cell layer does not extend all the way to the edges of the leaves, which therefore show the chlorophyll-deficient cells of other developmental layers. This is a periclinal chimera.]]

====Structure====
The distinction between sectorial, mericlinal and periclinal '''plant chimeras''' is widely used.<ref>{{cite book |last1=Kirk |first1=John Thomas Osmond |last2=Tilney-Bassett |first2=Richard A. E. |title=The plastids, their chemistry, structure, growth, and inheritance |date=1978 |publisher=Elsevier/North Holland Biomedical Press |isbn=9780444800220 |edition=Rev. 2d |url=https://books.google.com/books?id=z5LwAAAAMAAJ |access-date=9 February 2020}}</ref><ref>{{cite journal |last1=van Harten |first1=A. M. |title=Mutation Breeding Techniques and Behaviour of Irradiated Shoot Apices of Potato |date=1978 |journal=Agricultural Research Reports |issue=873 |publisher=Centre for Agricultural Publishing and Documentation (PUDOC) |location=Wageningen, Netherlands |isbn=978-90-220-0667-2 |url=https://books.google.com/books?id=c0JLPwAACAAJ |access-date=9 February 2020 |language=en}}</ref> Periclinal chimeras involve a genetic difference that persists in the descendant cells of a particular [[meristem]] layer. This type of chimera is more stable than mericlinal or sectoral mutations that affect only later generations of cells.<ref>{{citation |url=https://propg.ifas.ufl.edu/03-genetic-selection/04-genetic-chimera.html |title=Chimeras |access-date=12 October 2024}}</ref>

====Graft chimeras====
{{Main|Graft-chimaera}}

[[File:Taxus-mosaic1.JPG|thumb|upright|[[Taxus]] mosaic]]

These are produced by grafting genetically different parents, different [[cultivar]]s or different species (which may belong to different genera). The tissues may be partially fused together following [[grafting]] to form a single growing organism that preserves both types of tissue in a single shoot.<ref>{{cite journal |author1=Norris, R. |author2=Smith, R.H. |author3=Vaughn, K.C. |name-list-style=amp| title=Plant chimeras used to establish de novo origin of shoots | journal=Science | year=1983 | pages=75–76 | volume=220 | doi=10.1126/science.220.4592.75 | issue=4592 | pmid=17736164|bibcode=1983Sci...220...75N |s2cid=38143321}}</ref> Just as the constituent species are likely to differ in a wide range of features, so the behavior of their [[Anticline#Anticline terminology|periclinal]] chimeras is like to be highly variable.<ref>{{cite book |last1=Tilney-Bassett |first1=Richard A. E. |title=Plant Chimeras |date=1991 |publisher=[[Cambridge University Press]] |isbn=978-0-521-42787-6 |url=https://books.google.com/books?id=9rxMGwAACAAJ |access-date=9 February 2020 |language=en}}</ref> The first such known chimera was probably the [[Bizzarria]], which is a fusion of the [[Florentine citron]] and the [[sour orange]]. Well-known examples of a graft-chimera are [[+Laburnocytisus 'Adamii'|''Laburnocytisus'' 'Adamii']], caused by a fusion of a ''[[Laburnum]]'' and a [[Broom (shrub)|broom]], and "Family" trees, where multiple varieties of apple or pear are grafted onto the same tree. Many fruit trees are cultivated by grafting the body of a sapling onto a [[rootstock]].<ref>{{Cite web|url=https://extension.unh.edu/resource/growing-fruit-grafting-fruit-trees-home-orchard-fact-sheet|title=Growing Fruit: Grafting Fruit Trees in the Home Orchard [fact sheet] {{!}} UNH Extension|website=extension.unh.edu|date=17 January 2018|language=en|access-date=2020-02-23}}</ref>

====Chromosomal chimeras====
These are chimeras in which the layers differ in their [[chromosome]] constitution. Occasionally, chimeras arise from loss or gain of individual chromosomes or chromosome fragments owing to [[cell division|misdivision]].<ref>{{cite journal |author1=Thompson, J.D. |author2=Herre, E.A. |author3=Hamrick, J.L. |author4=Stone, J.L. |name-list-style=amp| title= Genetic Mosaics in strangler Fig Trees: Implication for Tropical Conservation | journal=Science | year=1991 | pages=1214–1216 | volume=254 | issue=5035 | doi= 10.1126/science.254.5035.1214 | pmid=17776412|bibcode=1991Sci...254.1214T |s2cid=40335585}}</ref> More commonly cytochimeras have simple multiple of the normal chromosome complement in the changed layer. There are various effects on cell size and growth characteristics.

====Nuclear gene-differential chimeras====
These chimeras arise by spontaneous or induced mutation of a nuclear gene to a dominant or recessive allele. As a rule, one character is affected at a time in the leaf, flower, fruit, or other parts.{{Citation needed|date=January 2017}}

====Plastid gene-differential chimeras====
These chimeras arise by spontaneous or induced mutation of a plastid gene, followed by the sorting-out of two kinds of plastid during vegetative growth. Alternatively, after selfing or [[nucleic acid thermodynamics]], plastids may sort-out from a mixed egg or mixed zygote respectively. This type of chimera is recognized at the time of origin by the sorting-out pattern in the leaves. After sorting-out is complete, periclinal chimeras are distinguished from similar looking nuclear gene-differential chimeras by their [[mendelian inheritance|non-mendelian inheritance]]. The majority of variegated-leaf chimeras are of this kind.{{Citation needed|date=January 2017}}

All plastid gene- and some nuclear gene-differential chimeras affect the color of the plasmids within the leaves, and these are grouped together as [[chlorophyll]] chimeras, or preferably as variegated leaf chimeras. For most variegation, the mutation involved is the loss of the [[chloroplast]]s in the mutated tissue, so that part of the plant tissue has no green pigment and no [[Photosynthesis|photosynthetic]] ability. This mutated tissue is unable to survive on its own, but it is kept alive by its partnership with normal photosynthetic tissue. Sometimes chimeras are also found with layers differing in respect of both their nuclear and their plastid genes.{{Citation needed|date=January 2017}}

====Origins====
There are multiple reasons to explain the occurrence of plant chimera during the plant recovery stage:

# The process of shoot [[organogenesis]] starts from the multicellular origin.<ref>{{cite journal |last1=Zhu |first1=X. |last2=Zhao |first2=M. |last3=Ma |first3=S. |last4=Ge |first4=Y. |last5=Zhang |first5=M. |last6=Chen |first6=L. |name-list-style=amp| title=Induction and origin of adventitious shoots from chimeras of Brassica juncea and Brassica oleracea | journal=Plant Cell Reports | year=2007 | pages=1727–1732 | volume=26 | issue=10 | doi=10.1007/s00299-007-0398-4|pmid=17622536 |s2cid=23069396}}</ref>
# The endogenous tolerance leads to the ineffectiveness of the weak selective agents.
# A self-protection mechanism (cross protection). Transformed cells serve as guards to protect the untransformed ones.<ref>{{cite journal |vauthors=Park SH, Rose SC, Zapata C, Srivatanakul M | title= Cross-protection and selectable marker genes in plant transformation. | journal= In Vitro Cellular & Developmental Biology – Plant| year=1998 | pages=117–121 | volume=34 | issue=2 | doi= 10.1007/BF02822775 | s2cid= 30883689}}</ref>
# The observable characteristic of transgenic cells may be a transient expression of the marker gene. Or it may due to the presence of agrobacterium cells.{{Citation needed|date=January 2017}}

=====Detection=====
Untransformed cells should be easy to detect and remove to avoid chimeras. This is because it is important to maintain the stable ability of the transgenic plants across different generations. Reporter genes such as [[GUS reporter system|GUS]] and [[Green Fluorescent Protein]]<ref>{{cite journal |last1=Rakosy-Tican |first1=E. |last2=Aurori |first2=C. M. |last3=Dijkstrav |first3=C. |last4=Thieme |first4=R. |last5=Aurori |first5=A. |last6=Davey |first6=M. R. |name-list-style=amp | title=The usefulness of the gfp reporter gene for monitoring Agrobacterium-mediated transformation of potato dihaploid and tetraploid genotypes | journal=Plant Cell Reports | year=2007 | pages=661–671 | volume=26 | issue=5 | doi=10.1007/s00299-006-0273-8|pmid=17165042 |s2cid=30548375}}</ref> (GFP) are used in combination with plant selective markers (herbicide, antibody etc.). However, GUS expression depends on the plant development stage and GFP may be influenced by the green tissue autofluorescence. [[Quantitative PCR]] could be an alternative method for chimera detection.<ref>{{cite journal | last1=Faize |first1=M. | last2=Faize |first2=L. | last3=Burgos |first3=L. | title=Using quantitative real-time PCR to detect chimeras in transgenic tobacco and apricot and to monitor their dissociation | journal=BMC Biotechnology | year=2010 | pages=53 | volume=10 | issue=1 | doi=10.1186/1472-6750-10-53| pmid=20637070 | pmc=2912785 | doi-access=free }}</ref>

===Viruses===
{{main|Chimera (virus)}}
[[File:Boiling Springs Lake (8553656936).jpg|thumb|upright|Boiling Springs Lake, California, is where the first natural chimeric virus was found in 2012.<ref name=diemer12 />]]

In 2012, the first example of a naturally-occurring RNA-DNA hybrid virus was unexpectedly discovered during a [[metagenomic]] study of the acidic extreme environment of [[Geothermal areas in Lassen Volcanic National Park#Boiling Springs Lake|Boiling Springs Lake]] that is in [[Lassen Volcanic National Park]], California.<ref name=diemer12/><ref name=thompson12>{{cite news |last=Thompson |first=Helen |date=19 April 2012 |url=https://www.nature.com/news/hot-spring-yields-hybrid-genome-1.10492 |title=Hot spring yields hybrid genome |work=Nature News |access-date=27 March 2020}}</ref> The virus was named BSL-RDHV (Boiling Springs Lake RNA DNA Hybrid Virus).<ref name=devor12>{{cite magazine |last=Devor |first=Caitlin |date=12 July 2012 |url=https://www.jyi.org/2012-july/2012/7/12/scientists-discover-hybrid-virus |title=Scientists discover hybrid virus |magazine=Journal of Young Investigators |access-date=31 March 2020}}</ref> Its [[genome]] is related  to a DNA [[circovirus]], which usually infects birds and pigs, and a RNA [[tombusvirus]], which infect plants. The study surprised scientists, because DNA and RNA viruses vary and the way the chimera came together was not understood.<ref name=diemer12/><ref name="sdaily">{{cite web |author=BioMed Central |date=18 April 2012 |url=https://www.sciencedaily.com/releases/2012/04/120418204353.htm |title=Could a newly discovered viral genome change what we thought we knew about virus evolution? |work=ScienceDaily |access-date=March 31, 2020}}</ref>

Other viral chimeras have also been found, and the group is known as the CHIV viruses ("chimeric viruses").<ref name=koonina15>{{cite journal |last1=Koonina |first1=Eugene V. |last2=Doljab |first2=Valerian V. |last3=Krupovic |first3=Mart |date=May 2015 |url=https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5898234&blobtype=pdf |title=Origins and evolution of viruses of eukaryotes: The ultimate modularity |journal=Virology |volume=41 |issue=5 |pages=285–293 |doi=10.2535/ofaj1936.41.5_285 |pmid=5898234|doi-access=free }}</ref>