When clinicians first peeked at the developing embryos in the uterus of an Australian mother-to-be, they found a not-uncommon phenomenon: a pair of 6-week embryos, each inside its own amniotic sac but sharing an outer sac. Totally normal for identical twins, and that’s exactly what everyone assumed the embryos were.
But a scan in the second trimester showed that one of the fetuses was developing as male and the other as female. Somehow, the two occupied a single outer sac—considered solely a feature of identical twins—yet these twins were different sexes. Genetic analysis of the amniotic fluid deepened the mystery: the twins were each a chimera—a mix of XX and XY DNA, but in different ratios. One twin, who was developing as male, was about 50:50 for cells carrying XX and XY genes. The second twin, who was developing as female, was more 90:10.
That meant that somehow, each twin had picked up an X and a Y from their father and ended up with different ratios of cells carrying them. Further genetic analysis showed that the twins did not have identical DNA. Instead, they had 100 percent identical genes from their mother only. They had only 77 percent of genes from their father in common, instead of the 100 percent identical twins have.
How did it happen? At fertilization, the egg cell usually offers up a single copy of DNA. Fusion with the sperm adds in the sperm’s DNA, completing the paired set. Paired chromosome sets restored, embryonic development moves forward, cell division after cell division.
In the case of these semi-identical twins—researchers call them “sesquizygotic”—the egg seems to have duplicated its own DNA, making two identical copies, each with an identical X chromosome. At or about the same time, two sperm, instead of one, made it past a number of daunting obstacles to fertilize the egg. At that point (maybe), each copy of their DNA also duplicated. One sperm carried a Y chromosome, and the other carried an X, and their DNA was similar, but not identical.
The result was a cell containing two identical copies of maternal DNA, two identical copies from an X-bearing sperm, and two identical copies from a Y-bearing sperm. It was quite a party with six sets of chromosomes when the usual post-fertilization expectation is two.
Making the best out of a very strange thing, the resulting cell with three pairs of chromosome sets went about some unusual allocations. One of the X-bearing maternal chromosome sets joined up with one of Y-bearing sperm sets. The other X-bearing maternal set joined forces with the X-bearing sperm set. The result: cells bearing an XX signature and cells bearing an XY combination. Left out in the cold: the remaining two sperm chromosome sets, one X and one Y. They may well have made a valiant effort, but paternal–paternal chromosome pairings fail embryonically in mammals.
Each of the new maternal–paternal pairings then went about the business of cell division, creating a ball of embryonic cells. In this case, some were XX and some were XY. At a stage where identical twins often form, a set of these cells that was about a 50:50 mix of XX:XY cells was dedicated to forming one twin, which would develop as male. Another set of cells, with about a 90:10 mix of XX:XY cells, entered into the process for the second twin, which would develop as female. Each twin has the same X and other 22 chromosomes from their mother, but the two sperm from their father gave them different sets of DNA, making them not quite identical.
The researchers who solved this mystery and published their findings in the New England Journal of Medicine naturally wondered how common it might be. After all, other brother–sister twin pairs born without the benefit of ultrasound confirmation might also be semi-identical instead. Their review of 968 twin pairs turned up no hits. So, semi-identical twinning is a truly rare event.
The upshot for the twins, who not only are semi-identical but also chimeras, is a mixed bag. They are 4-and-a-half years old. Although the boy overall has experienced what looks like typically male development, the girl has had to deal with more issues.
Just after birth, she developed a rash on her arm that suggested a blood clot, something that arose just before birth. Clot-busting therapy did not work, and doctors had to amputate her arm just below the shoulder. Her brother does not seem to have any clotting issues. In addition, doctors removed the girl’s ovaries because they had not developed into functional gonadal tissue, a condition called gonadal dysgenesis that causes concern for later cancer.