Chimera

Animals

Although some chimeras do arise naturally, most are produced experimentally, either by mixing cells of very early embryos or by tissue grafting in late embryos or adults. Experimental chimeras have been used to study a number of biological questions, including the origin and fate of cell lineages during embryonic development, immunological self-tolerance, tumor susceptibility, and the nature of malignancy.

Two techniques used to form chimeras by mixing embryo cells are aggregation and injection.

Aggregation chimeras are produced by a technique that involves removing the zonae pellucidae from around 8–16 cell embryos of different strains of mice and pushing the morulae together so that the cells can aggregate. After a short period of laboratory culture, during which the aggregate develops into a single large blastocyst, the embryo is returned to a hormone-primed foster mother. Chimeric offspring are recognized in several ways. If derived from embryos of pigmented and albino strains, they may have stripes of pigmented skin and patches of pigment in the eye. Internal chimerism can be detected by use of chromosomal markers or genetically determined enzyme variants. Chimeras accept skin grafts from the two component strains, but reject grafts from third-party strains.

Injection chimeras are produced by a technique in which a blastocyst of the host mouse strain of mouse embryos is removed from its zona pellucida and held on a suction pipette. Cells of the donor strain are injected through a fine glass needle, either into the blastocoele cavity or into the center of the inner cell mass (the group of cells from which the fetus is derived). After a short period of culture, the blastocyst is returned to a foster mother.

Another kind of cell—the pluripotent stem cell of mouse teratocarcinomas—was found to give rise to normal tissues in adult chimeras after injection into the mouse blastocyst. Teratocarcinomas are tumors consisting of a disorganized mixture of adult and embryonic tissues. They develop spontaneously from germ cells in the gonads of certain mouse strains, or from cells in early embryos transplanted to ectopic sites. All the differentiated tissues in the tumor arise from pluripotent stem cells known as embryonal carcinoma (EC) cells. When embryonal carcinoma cells are injected into a genetically marked host blastocyst, they continue to divide and participate in normal development, and give rise to fully differentiated cells in all tissues of the adult, including skin, muscle, nerve, kidney, and blood. Embryonal carcinoma cells from several sources, including spontaneous and embryo-derived tumors and cultured lines selected to carry specific mutations or even human chromosomes, have contributed to normal chimeras. However, embryonal carcinoma cells from some other sources fail to integrate, but produce teratocarcinomas in the newborn animal or adult. The fact that certain embryonal carcinoma cells give rise to tumors when injected under the skin or into the body cavity, but behave normally in the blastocyst, has been used to support the idea that cancers can develop not only as a result of gene mutations but also as a result of disturbances in environmental factors controlling normal cell differentiation (epigenetic theory of cancer).

Animals that have accepted skin or organ grafts are technically chimeras. Radiation chimeras are produced when an animal is exposed to x-rays, so that blood-forming stem cells in the bone marrow are killed and then replaced by a bone marrow transplant from a genetically different animal. Lymphoid cells in the process of differentiating from stem cells in the donor marrow recognize the recipient as “self” and do not initiate an immune response against the host cells. See Transplantation biology

Naturally occurring chimeras in humans are not rare and are most easily recognized when some cells are XX and others XY. Such individuals are usually hermaphrodite and probably result from fertilization of the egg by one sperm and the second polar body by another, with both diploid cells then contributing to the embryo (the small polar bodies normally degenerate). Blood chimeras are somewhat more common in animals such as cattle where the blood vessels in placentas of twins fuse, so that blood cells can pass from one developing fetus to the other.

Plants

In modern botanical usage a chimera is a plant consisting of two or more genetically distinct kinds of cells. Chimeras can arise either by a mutation in a cell in some part of the plant where cells divide or by bringing together two different plants so that their cells multiply side by side to produce a single individual. They are studied not only because they are interesting freaks or ornamental, but also because they help in the understanding of many of the developmental features of plants that would otherwise be difficult to investigate.

The first type of chimera to be used in this way resulted from grafting. Occasionally a bud forms at the junction of the scion and stock incorporating cells from both, and it sometimes happens that the cells arrange themselves so that shoots derived from the bud will contain cells from both plants forever.

Flowering plants have growing points (apical meristems) where the outer cells are arranged in layers parallel to the surface. This periclinal layering is due to the fact that the outer cells divide only anticlinally, that is, by walls perpendicular to the surface of the growing point. In many plants there are two such tunica layers and, because cell divisions are confined to the anticlinal planes, each layer remains discrete from the other and from the underlying nonlayered tissue called the corpus. The epidermis of leaves, stems, and petals is derived from the outer layer of the growing point. See Apical meristem

With a periclinal chimera it is possible to trace into stems, leaves, and flowers which tissues are derived from each layer in the growing point. For leaves, this can also be done with variegated chimeras where the genetic difference between the cells rests in the plastids resulting from mutation whose effect is to prevent the synthesis of chlorophyll. Tracts of cells whose plastids lack this pigment appear white or yellow. A common form of variegated chimera has leaves with white margins and a green center (see illustration). The white margin is derived from the second layer of the tunica, and the green center is derived from inner cells of the growing point. The white leaf tissue overlies the green in the center of the leaf, but does not mask the green color. Chimeras with green leaf margins and white centers are usually due to a genetically green tunica proliferating abnormally at the leaf margin in an otherwise white leaf.

Variegated Pelargonium, a periclinal chimera whose second tunica layer is genetically white and whose corpus is genetically green

Since the somatic mutation that initiates chimeras would normally occur in a single cell of a growing point or embryo, it often happens that it is propagated into a tract of mutant cells to form a sector of the plant. If the mutation resulted in a failure to form green pigment, the tract would be seen as a white stripe. Such chimeras are called sectorial, but they are normally unstable because there is no mechanism to isolate the mutant sector and, in the flux that occurs in a meristem of growing and dividing cells, one or other of the two sorts of cells takes over its self-perpetuating layer in the growing point. The sectorial chimera therefore becomes nonchimerical or else a periclinal chimera.

However, in one class of chimera an isolating mechanism can stabilize the sectorial arrangement. This propagates stripes of mutant tissue into the shoot, but because the tunica and corpus are discrete from each other, the plant is not fully sectored and is called a mericlinal chimera. Many chimeras of this type have a single tunica layer; those with green and white stripes in the leaves have the mutant cells in sectors of the corpus. They are always plants with leaves in two ranks, and consequently the lateral growth of the growing point occurs by cell expansion only in the plane connecting alternate leaves. This results in the longitudinal divisions of the corpus cells being confined to planes at right angles to the plane containing the leaves. A mutation in one cell therefore can result in a vertical sheet of mutant cells which, in the case of plastid defect, manifests itself as a white stripe in every future leaf.

The growing points of roots may also become chimerical, but in roots there is no mechanism to isolate genetically different tissues as there is in shoots, and so chimeras are unstable.

Since the general acceptance of the existence of organisms with genetically diverse cells, many cultivated plants have been found to be chimeras. Flecks of color often indicate the chimerical nature of such plants. Color changes in potato tubers occur similarly because the plants are periclinal chimeras. See Somatic cell genetics

(1) In Greek mythology, a monster with the head and neck of a lion, the body of a goat, and the tail of a dragon. The Chimeras were the offspring of Typhon and Echidna. In a figurative sense, the term “chimera” refers to an unfounded, unrealizable dream.

(2) In the plastic arts, sculptural representations of fantastic monsters that embodied vices, evil powers, and the like. Characteristic of the Gothic, they were used as part of the ornamentation of a cathedral. Particularly famous are the chimeras at the bases of the towers of Notre Dame Cathedral in Paris.

an organism or part of an organism that consists of genetically heterogeneous tissues. The term was first used in 1907 by the German botanist G. Winckler, for plant forms obtained by combining nightshade and tomato. In 1909, E. Baur, while studying variegated pelargonium, explained the nature of chimeras. Mosaic chimeras, or hyperchimeras, have genetically heterogeneous tissues that form a subtle mosaic. In sectorial chimeras the heterogeneous tissues are arranged in large areas, in periclinal chimeras the tissues lie in layers upon one another, and in mericlinal chimeras the tissues consist of a mixture of sectorial and periclinal areas.

Chimeras may result from grafting or from mutations of somatic cells. The components of chimeras may differ from one another in the genes of the nuclei and in the number of chromosomes or genes in the plastids and other elements of the cytoplasm. The leaf markings of periclinal chimeras depend on how many layers of meristematic tissue at the growing point participate in the formation of the leaf. In dicotyledonous plants the pulp of the leaf margin is most often formed by the second layer (diplochlamydeous chimeras, for example, pelargoniums with white-edged leaves); in monocotyledons, the leaf margin is formed by the first layer (haplochlamydeous chimeras, for example, Chlorophytum with white-edged leaves).

The offspring of a chimera corresponds to the tissue from which it is descended. The generative cells of plants originate from the second layer of the growing point; hence, the offspring of periclinal chimeras correspond to the genotype of that layer. Interaction between the components of a chimera and the transfer of various substances from one component to another lead to developmental anomalies and sometimes to infertility. Under certain conditions, especially in graft chimeras, sections of chromosomes may move from one component to another and may be included in the chromosomes of the cells of the second component, changing the characters of the plant.

In horticultural practice many chimeras that originated accidentally as a result of grafting continue to be cultivated. Examples are chimeras from orange and lemon plants and from the brooms Cytisus purpureus and C. laburnum. Various chimeras of medlar and hawthorn are used in research. An example of a chimera in animals are calves from a single litter whose blood contains a mixture of red corpuscles of different blood groups.