Chimera (genetics)
A genetic chimerism or chimera (/kaɪˈmɪərə/ ky-MEER-ə or /kɪˈmɪərə/ kim-EER-ə) is a single organism composed of cells with more than one distinct genotype. In animals and human chimeras, this means an individual derived from two or more zygotes, which can include possessing blood cells of different blood types, and subtle variations in form (phenotype). Animal chimeras are produced by the merger of two (or more) embryos. In plant chimeras, however, the distinct types of tissue may originate from the same zygote, and the difference is often due to mutation during ordinary cell division. Normally, genetic chimerism is not visible on casual inspection; however, it has been detected in the course of proving parentage.[1] In contrast, an individual where each cell contains genetic material from two organisms of different breeds, varieties, species or genera is called a hybrid.[2]
Another way that chimerism can occur in animals is by organ transplantation, giving one individual tissues that developed from a different genome. For example, transplantation of bone marrow often determines the recipient's ensuing blood type.[citation needed].
Classifications
Natural and obligate chimerism
Some level of chimerism occurs naturally in the wild in many animal species, however in some cases may be a required (obligate) part of their life cycle.
Symbiotic chimerism in anglerfish
Chimerism occurs naturally in adult
Sponges
Chimerism has been found in some species of marine sponges.[4] Four distinct genotypes have been found in a single individual, and there is potential for even greater genetic heterogeneity. Each genotype functions independently in terms of reproduction, but the different intra-organism genotypes behave as a single large individual in terms of ecological responses like growth.[4]
In obligates
It has been shown that yellow crazy ants are obligate chimeras, the first known such case. In this species, the queens have arisen from fertilized eggs with a genotype of RR (Reproductive x Reproductive), the sterile female workers show a RW arrangement (Reproductive x Worker), and the males instead of being haploid as is usually the case for ants also display a RW genotype, but for them the egg R and the sperm W do not fuse so they develop as a chimera with some cells carrying an R and others carrying a W genome.[5][6]
Artificial chimerism
Artificial chimerism refers to examples of chimerism that are intentionally produced by humans, either for research purposes or commercial purposes.
Tetragametic chimerism
Tetragametic chimerism is a form of congenital chimerism. This condition occurs through the fertilization of two separate ova by two sperm, followed by aggregation of the two at the blastocyst or zygote stages. This results in the development of an organism with intermingled cell lines. Put another way, the chimera is formed from the merging of two nonidentical twins (a similar merging presumably occurs with identical twins, but as their genotypes are not significantly distinct, the resulting individual would not be considered a chimera). As such, they can be male, female, or have mixed intersex characteristics.[7][8][9][10][11][12][13][excessive citations]
The tetragametic state has important implications for organ or
Microchimerism
Microchimerism is the presence of a small number of cells that are genetically distinct from those of the host individual. Most people are born with a few cells genetically identical to their mothers' and the proportion of these cells goes down in healthy individuals as they get older. People who retain higher numbers of cells genetically identical to their mother's have been observed to have higher rates of some autoimmune diseases, presumably because the immune system is responsible for destroying these cells and a common immune defect prevents it from doing so and also causes autoimmune problems.
The higher rates of autoimmune diseases due to the presence of maternally-derived cells is why in a 2010 study of a 40-year-old man with scleroderma-like disease (an autoimmune rheumatic disease), the female cells detected in his blood stream via FISH (fluorescence in situ hybridization) were thought to be maternally-derived. However, his form of microchimerism was found to be due to a vanished twin, and it is unknown whether microchimerism from a vanished twin might predispose individuals to autoimmune diseases as well.[14] Mothers often also have a few cells genetically identical to those of their children, and some people also have some cells genetically identical to those of their siblings (maternal siblings only, since these cells are passed to them because their mother retained them).[citation needed]
Germline chimerism
Germline chimerism occurs when the germ cells (for example,
Types
Animals
As the organism develops, it can come to possess
This is particularly true for the
In the budgerigar, due to the many existing plumage colour variations, tetragametic chimeras can be very conspicuous, as the resulting bird will have an obvious split between two colour types - often divided bilaterally down the centre. These individuals are known as half-sider budgerigars.[22]
An animal chimera is a single organism that is composed of two or more different populations of genetically distinct cells that originated from different zygotes involved in sexual reproduction. If the different cells have emerged from the same zygote, the organism is called a 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 chimeras have been documented.[18]
Chimerism in Humans
Some consider mosaicism to be a form of chimerism,[23] while others consider them to be distinct.[24][25][26]
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.[26]
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.[27] 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".[28]
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.[29]
While German
This condition is either innate or it is synthetic, acquired for example through the infusion of
In nonidentical twins, innate chimerism occurs by means of blood vessel
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. ".[31]
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 downwards from the shoulders down to the lower back; this is one expression of pigment unevenness called Blaschko's lines.[32]
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 she was not their mother.[18][33]
Plants
Structure
The distinction between sectorial, mericlinal and periclinal plant chimeras are widely used.[34][35]
Graft chimeras
These are produced by grafting genetically different parents, different
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 misdivision.[39] 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]
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 non-mendelian inheritance. The majority of variegated-leaf chimeras are of this kind.[citation needed]
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 chloroplasts in the mutated tissue, so that part of the plant tissue has no green pigment and no 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]
Origins
There are multiple reasons to explain the occurrence of plant chimera during the plant recovery stage:
(1) The process of shoot organogenesis starts form the multicellular origin.[40]
(2) The endogenous tolerance leads to the ineffectiveness of the weak selective agents.
(3) A self-protection mechanism (cross protection). Transformed cells serve as guards to protect the untransformed ones.[41]
(4) 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]
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
Viruses
In 2012, the first example of a naturally-occurring RNA-DNA hybrid virus was unexpectedly discovered during a
Other viral chimeras have also been found, and the group is known as the CHIV viruses ("chimeric viruses").[48]
Research
The first known primate chimeras are the rhesus monkey twins, Roku and Hex, each having six genomes. They were created by mixing cells from
A major milestone in chimera experimentation occurred in 1984 when a chimeric
To research the developmental biology of the bird embryo, researchers produced artificial quail-chick chimeras in 1987. By utilizing transplantation and ablation in the chick embryo stage, the neural tube and the neural crest cells of the chick were ablated, and replaced with the same parts from a quail.[50] Once hatched, the quail feathers were visibly apparent around the wing area, whereas the rest of the chick's body was made of its own chicken cells.
In August 2003, researchers at the
In 2023 a study reported the first chimeric monkey using embryonic stem cell lines, it was the only live birth from 12 pregnancies resulting from 40 implanted embryos of the crab-eating macaque, an average of 67% and a highest of 92% of the cells across the 26 tested tissues were descendants of the donor stem cells against 0.1–4.5% from previous experiments on chimeric monkeys.[52][53][54]
Work with mice
Chimeric mice are important animals in biological research, as they allow for the investigation of a variety of biological questions in an animal that has two distinct genetic pools within it. These include insights into problems such as the tissue specific requirements of a gene, cell lineage, and cell potential.
The general methods for creating chimeric mice can be summarized either by injection or aggregation of embryonic cells from different origins. The first chimeric mouse was made by
Underlying biology
The ability to make mouse chimeras comes from an understanding of early mouse development. Between the stages of fertilization of the egg and the implantation of a blastocyst into the uterus, different parts of the mouse embryo retain the ability to give rise to a variety of cell lineages. Once the embryo has reached the blastocyst stage, it is composed of several parts, mainly the
It is possible to dissect the embryo at other stages so as to accordingly give rise to one lineage of cells from an embryo selectively and not the other. For example, subsets of blastomeres can be used to give rise to chimera with specified cell lineage from one embryo. The Inner Cell Mass of a diploid blastocyst, for example, can be used to make a chimera with another blastocyst of eight-cell diploid embryo; the cells taken from the inner cell mass will give rise to the primitive endoderm and to the epiblast in the chimera mouse.[61] From this knowledge,
Methods of production
There are a variety of combinations that can give rise to a successful chimera mouse and – according to the goal of the experiment – an appropriate cell and embryo combination can be picked; they are generally but not limited to diploid embryo and ES cells, diploid embryo and diploid embryo, ES cell and tetraploid embryo, diploid embryo and tetraploid embryo, ES cells and ES cells. The combination of embryonic stem cell and diploid embryo is a common technique used for the making of chimeric mice, since gene targeting can be done in the embryonic stem cell. These kinds of chimeras can be made through either aggregation of stem cells and the diploid embryo or injection of the stem cells into the diploid embryo. If embryonic stem cells are to be used for gene targeting to make a chimera, the following procedure is common: a construct for homologous recombination for the gene targeted will be introduced into cultured mouse embryonic stem cells from the donor mouse, by way of electroporation; cells positive for the recombination event will have antibiotic resistance, provided by the insertion cassette used in the gene targeting; and be able to be positively selected for.[64][65] ES cells with the correct targeted gene are then injected into a diploid host mouse blastocyst. Then, these injected blastocysts are implanted into a pseudo pregnant female surrogate mouse, which will bring the embryos to term and give birth to a mouse whose germline is derived from the donor mouse's ES cells.[66] This same procedure can be achieved through aggregation of ES cells and diploid embryos, diploid embryos are cultured in aggregation plates in wells where single embryos can fit, to these wells ES cells are added the aggregates are cultured until a single embryo is formed and has progressed to the blastocyst stage, and can then be transferred to the surrogate mouse.[67]
Ethics and legislation
The US and Western Europe have strict codes of ethics and regulations in place that expressly forbid certain subsets of experimentation using human cells, though there is a vast difference in the regulatory framework.[68] Through the creation of human chimeras comes the question: where does society now draw the line of humanity? This question poses serious legal and moral issues, along with creating controversy. Chimpanzees, for example, are not offered any legal standing, and are put down if they pose a threat to humans. If a chimpanzee is genetically altered to be more similar to a human, it may blur the ethical line between animal and human. Legal debate would be the next step in the process to determine whether certain chimeras should be granted legal rights.[69] Along with issues regarding the rights of chimeras, individuals have expressed concern about whether or not creating human chimeras diminishes the "dignity" of being human.[70]
See also
References
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Another form of chimera is the mosaic, which is a composite individual derived from a single fertilized egg.
- ISSN 1769-7212.
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
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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.
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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.
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Further reading
- Yu N, Kruskall MS, Yunis JJ, Knoll JH, Uhl L, Alosco S, Ohashi M, Clavijo O, Husain Z, Yunis EJ, Yunis JJ, Yunis EJ (2002). "Disputed maternity leading to identification of tetragametic chimerism". N Engl J Med. 346 (20): 1545–52. PMID 12015394.
- Appel, Jacob M. "The Monster's Law", Genewatch, Volume 19, Number 2, March–April 2007.
- Nelson, J. Lee (Scientific American, February 2008). Your Cells Are My Cells
- Weiss, Rick (August 14, 2003). Cloning yields human-rabbit hybrid embryo Archived 2012-10-25 at the Wayback Machine. The Washington Post.
- Weiss, Rick (February 13, 2005). U.S. Denies Patent for a too-human hybrid. The Washington Post.
- L. M. Repas-Humpe; A. Humpe; R. Lynen; B. Glock; E. M. Dauber; G. Simson; W. R. Mayr; M. Köhler; S. Eber (1999). "A Dispermic Chimerism in a 2-year-old Caucasian Boy". Annals of Hematology. 78 (9): 431–434. S2CID 24655050.
- Strain, Lisa; Dean, John C.S.; Hamilton, Mark P.R.; Bonthron, David T. (1998). "A True Hermaphrodite Chimera Resulting from Embryo Amalgamation after in Vitro Fertilization". New England Journal of Medicine. 338 (3): 166–9. PMID 9428825.
- Jones, David Albert; MacKellar, Calum, eds. (2012). Chimera's Children: Ethical, Philosophical and Religious Perspectives on Human-Nonhuman Experimentation. London: Continuum Books. ISBN 9781441195807.
External links
- "Chimerism Explained"
- Chimerism and cellular mosaicism, Genetic Home Reference, U.S. National Library of Medicine, National Institute of Health.
- Chimera: Apical Origin, Ontogeny and Consideration in Propagation
- Plant Chimeras in Tissue Culture Archived 2013-10-03 at the Wayback Machine
- Ainsworth, Claire (November 15, 2003). "The Stranger Within". New Scientist (subscription required) Archived 2008-10-22 at the Wayback Machine. (Reprinted here [2])
- Embryogenesis of chimeras, twins and anterior midline asymmetries
- Natural human chimeras: A review