Part lion, part goat, and part snake, the fire-breathing Chimera is one fearsome creature. Its siblings include the Hydra and Cerberus according to Greek mythology. Nowadays, the term chimera is used to describe any organism that is comprised of cells from two separate zygotes. In the lab, chimeras can be created by combining the cells of two different embryos or, later during development, the transplantation of tissue from one organism to the other. Outside of experimental biology or transplant surgery, chimeras were thought to be extremely rare. With the advent of next-generation sequencing technology, we are learning that more often that not, we aren't who we think we are.
An article in the Science Times gives one extreme example of this. A woman in need of a transplant was searching for donors when test results indicated that she was not the biological mother of 2 of her children. Her doctors determined that she was comprised of cells from two different genomes. Incredibly, her blood and some eggs contained one set of genes while the rest of her eggs contained another set! Her body was the product of two fertilized eggs!
We are even learning that during pregnancy, fetal cells can enter the mother's bloodstream and invade her other tissues, including the brain! A Canadian study of female brain tissue determined that 63% of their subjects' brains had male microchimerism. This means that the researchers found cells with Y chromosomes in more than half of these women's brains! Even though maternal and fetal blood do not mix during pregnancy, their son's cells somehow escaped from their own fetal circulatory systems, entered their mother's blood streams and settled in the brain. What's more interesting is that this study found a potential correlation between mental health and microchimerism. When compared to women with Alzheimer's Disease, women with no history of neurological disease were more likely to have microchimerism. Though the results are far from definitive, the data suggest that the persistence of fetal cells in the brain may confer some resistance to neurodegeneration. Researchers are also studying microchimerism in dogs and their litters to understand how foreign cells may affect inflammation and the immune response.
Another form of genomic inconsistency throughout an organism is mosaicism. In contrast to chimeras, mosaic organisms arise from a single zygote and they are also quite common. Half of all mammals are mosaic. Yes, this included humans. In mammals, mosaicism is one mechanism of regulating gene dosage. Recall that females have two X chromosomes, while males have one X chromosome and one Y chromosome. To prevent female cells from receiving a double dose of X chromosome genes, one of their sex chromosomes is silenced. This epigenetic event occurs at a multicellular stage. As a result, some cells transcribe genes from one X chromosome, while the other X chromosome is transcribed in a completely different set of cells. Calico cats are a classic example of mosaicism.
The earlier during development the difference arises, the more profound the outcome. For example, genetic changes at the two-cell stage results in bilateral mosaicism. In rare cases, mosaicism can result in a organism that is comprised of cells of different sexes. This type of mosaic is called a gynandromorph, and they are coveted by butterfly collectors.
If you want to learn more about how chimeras can be used as a tool for research, listen to our interview with Dr. Richard Schneider, although the chimeras generated by his lab are of the quail-duck variety, not the lion-goat-snake variety.