Further Development 12.11: Chimerism

Birds and Mammals

The ability to produce an entire embryo from cells that normally would have contributed to only a portion of the embryo is seen in the ability of two or more early embryos to form one chimeric individual rather than twins, triplets, or a multiheaded individual. Chimeric mice can be produced by artificially aggregating two or more early-cleavage (usually 4- or 8-cell) embryos to form a composite embryo. Market and Petters (1978) have shown that three early 4-cell embryos can unite to form a common compacted morula and that the resulting mouse can have the coat colors of the three different strains. Moreover, they showed that each of the three embryos gave rise to precursors of the gametes. When a chimeric (black/brown/white) female mouse was mated to a white-furred (recessive) male, offspring of each of the three colors were produced.

There is even evidence that human embryos can form chimeras (de la Chappelle et al. 1974; Mayr et al. 1979; Yu et al 2002). Some individuals have two genetically different cell types (XX and XY) within the same body, each with its own set of genetically defined characteristics. The simplest explanation for such a phenomenon is that these individuals resulted from the aggregation of two embryos, one male and one female, that were developing at the same time. If this explanation is correct, then two fraternal twins have fused to create the individual (see Yu et al. 2002).

There are other explanations, at least for some chimeras. Souter and colleagues (2007) have shown that in at least one XX/XY human the maternal alleles were identical and the paternal alleles differed. This would be expected if the egg underwent parthenogenic activation (meiosis without sperm activation) and each of the meiotic cells was then fertilized by a different sperm (one bearing an X chromosome, one a Y). The intermingling of the cells would produce the chimera, which in the case recounted by Souter et al. was a true hermaphrodite, having both male and female sex organs. We still do not know the mechanisms through which human twins and chimeras form.

Literature Cited

de la Chappelle, A., J. Schröder, P. Rantanen, B. Thomasson, M. Niemi, A. Tilikainen, R. Sanger and E. E. Robson. 1974. Early fusion of two human embryos? Ann. Hum. Genet. 38: 63–75.

PubMed Link

Markert, C. L. and R. M. Petters. 1978. Manufactured hexaparental mice show that adults are derived from three embryonic cells. Science 202: 56–58.

PubMed Link

Mayr, W. R., V. Pausch and W. Schnedl. 1979. Human chimaera detectable only by investigation of her progeny. Nature 277: 210–211.

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Souter, V. L. and 9 others. 2007. A case of true hemaphroditism reveals an unusual mechanism of twinning. Hum. Genet. 121: 179–185.

PubMed Link

Yu, N. and 11 others. 2002. Disputed maternity leading to identification of tetragametic chaemerism. N. Eng. J. Med. 346: 1545–1552.

PubMed Link

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