Chimera (genetics)

The term chimera pertains to an organism that consists of cells from different zygotes. The terms was derived from Greek mythology, where a lion-like creature called Chimera presented different parts of various animals, including the head of a goat protruding from the back and a snake serving as its tail. In the field of genetics, a chimera represents an organism with variable body constituents. For example, an organism may have both male and female reproductive organs (also known as hermaphroditism) or an individual may present with two blood types. In other species, such as plants, cells that are derived from a single zygote may display chimerism by having differences in appearance or phenotype because other cells might have accumulated mutations that influence its further development and differentiation. Another example of a chimera is an individual who received an organ transplant such as a heart or a kidney from another individual.

Background

The first human chimera was reported in the United Kingdom in 1953, when a female patient showed different blood types during a routine blood test. Prior to this discovery, scientists believed that an individual could only possess a single type of blood, which could be A, B, O, or AB. However, the observation of two blood types in this patient prompted clinicians to repeat the blood typing test to rule out a mistake in sampling and/or analysis. The director of the hospital’s blood group unit then recalled a report on twin cattle that showed a mixture of blood types from gestation. They then determined that their female patient had had a twin who died within the first year after birth. They collected saliva from their patient, expecting Type O blood. They then concluded that their patient originally had Type O blood, yet received Type A blood during gestation from her twin. Based on these findings, the physicians reported that their patient was a chimera.

It is important to understand that chimeras naturally occur but also may be artificially generated. Natural chimeras often go undetected because these are developed prior to birth. Furthermore, the degree of variation in the DNA of natural chimeras may vary from one chimera to another, rendering it more difficult to detect. One of the most common examples of natural chimerism involves the presence of a small number of cells in a human being that were not derived or did not originate from that actual person. This type of natural chimerism, also known as fetomaternal microchimerism, frequently happens during pregnancy, when an exchange of cells occurs between the developing fetus and the mother. It is also possible for dizygotic twins, also known as fraternal (nonidentical) twins, which are two separate eggs that are simultaneously fertilized by individual sperms, to undergo cell exchange during fetal development. Studies have shown that mothers may carry fetal cells decades after they have given birth to their child, indicating that an exchange of cells occurred during pregnancy. Although the actual number of pregnancies that involve fetomaternal microchimerism remains unclear, there has been speculation that this occurs in almost every pregnancy. The biological mechanism underlying fetomaternal microchimerism also remains elusive; however, a number of hypotheses have been presented to explain this natural phenomenon.

One hypothesis is that fetomaternal microchimerism occurs when blood from the developing fetus travels via the umbilical cord to the mother’s placenta. In an ideal physiological setting, fetal blood is expected not to mix with maternal blood, and the thin placental wall facilitates in this separation. However, the placenta may develop microruptures, which in turn allow fetal and maternal blood to mix, thereby resulting in fetomaternal microchimerism. Another hypothesis is that fetal or maternal cells migrate across the placental wall, which has been observed to naturally occur during early stages of pregnancy. Studies have focused on the effects of fetal cells on the mother, particularly those relating to autoimmune disorders and malignancies.

Topic Today

Chimerism is a biological phenomenon that occurs in nature and in the laboratory setting. Studies have also shown that chimerism is a common activity that involves a wide range of species. Based on its incidence in nature, it is highly likely that humans may not even realize their own chimeric status unless these are discovered as incidental findings to a well-documented medical condition. It is thus highly likely that majority of human chimeras, and even those of other species, will remain unidentified or not be discovered.

Nevertheless, researchers have speculated that the incidence of chimerism is actually more common than had been originally established. There are also arguments that possibly every human being, at a certain point in his or her life, was chimeric. The majority of scientific commentators express their belief that the observed high incidence rate of chimerism in humans is due to fetomaternal microchimerism. However, there is also a small group of scientists who postulate that tetragametic chimerism, also known as congenital chimerism, or the simultaneous fertilization of two separate eggs by two separate sperm followed by fusion of the two embryos, occurs at a rate that is higher than previously suspected. These postulates therefore suggest that human chimerism is a common event among fraternal or dizygotic twins, possibly greater than 20 percent.

Despite the disagreements regarding the origin and mechanism underlying fetomaternal microchimerism, there is unity in the consequences of this biological phenomenon in relation to clinical technologies. Physicians and scientists believe that assisted reproductive technology, which is a collective term for various approaches that facilitate pregnancy, such as the administration of fertility drugs, artificial insemination, and in vitro fertilization, may also serve as an additional factor that could contribute to the increase in the incidence of tetragametic chimeras. Generally, the incidence of fraternal twins who are naturally born and not induced by a specific, assisted reproductive technology is one in thirty pregnancies. However, the incidence of twins in women who received fertility drugs or in vitro fertilization is higher by 20 to 40 percent. Additional investigations on this matter are necessary to better understanding the factors that contribute to these events.

Bibliography

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