Multiple Gestation Part 4: Sesquizygotic (Semi-Identical) Twins

Previously in this series, we discussed the main categories of multiple gestation. We noted that the broadest categories of twins are dizygotic (or multi-zygotic if there are more than two) and monozygotic twinning. In a dizygotic pregnancy, each twin each derived from its own zygote, its own egg that has been fertilized by a sperm. Similarly, there can be trizygotic triplets and higher order pregnancies with multiple zygotes. Genetically, such twins or triplets are like other siblings from the same pair of parents, meaning that they are not identical and can be either the same sex or one can be a boy and the other a girl. Known colloquially as fraternal twins, this is the more common situation, both in natural twinning and in twinning resulting from fertility treatment. We also discussed monozygotic twinning, which produces genetically identical twins, triplets, and so forth, and since they come from a common zygote they must be the same sex.

Whereas dizygotic twins share on average about 50 percent of their genome (50 percent of their DNA) just like any other siblings, monozygotic twins share 100 percent of their genome, which is why they are identical. They are like clones. But intermediate between the two categories dizygotic (~50 percent genome sharing) and monozygotic (100 percent genome sharing) is another type of twins. Known as sesquizygotic twins, such twins share more than 50 percent but less than 100 percent of their genome. Sometimes they are called semi-identical twins. The terminology itself is still developing, because it has been though that such twins are quite rare.

Just how rare sesquizygotic twins are is uncertain, because the discovery of a handful of such pairs has led to an idea that probably there are various others walking around, most of whom have been misidentified as dizygotic twins or as monozygotic twins. That’s because, if they are generally healthy, such twins would not necessarily undergo genetic testing, revealing that they are more identical than typical siblings, but less identical than monozygotic twins.

As for the terminology, the prefix  sesqui- means one and a half, relating to how you can expect such twins to share roughly 75% of the parts of the genome that vary among human beings. Keep in mind that when we talk about 50 percent shared, we are talking about 50 percent of the parts of the genome that are not already shared with all humans, or more accurately, more humans of the same sex. Being a human female, you have more in common genetically with many other human females outside your family than you have with your brothers. But if we disregard the sex chromosomes (the X and Y chromosomes), then brothers and sisters in the same family share more of their genomes than they do with the rest of the human population, regardless of sex.

Before we explore how sesquizygotic twins can come to exist, we need to discuss how the handful of known sesquizygotic twins have been discovered in the first place. In order to do this, we need to review a concept that we discussed earlier in this series, namely that there are different types of monozygotic twins. The discussion is a bit detailed, but it’s important because it relates to how twins are identified in the womb with ultrasound.

The most common type of monozygotic twins are called monochorionic diamniotic twins. These result from product of conception splitting in half roughly four to eight days after fertilization. This is the early part of the blastocyst stage, meaning that, prior to splitting, there already is a group of cells called trophoblasts, whose descendants will form the placenta. There is not yet an amniotic cavity, however, so, after the blastocyst splits into two, each new embryo will develop its own amnion, but the embryos will share a trophoblast. Consequently, they will end up sharing placenta in the later embryonic and fetal stages.

A more rare type of monozygotic twins, called dichorionic, diamniotic, result from the product of conception splitting earlier, from day one to day three after fertilization, meaning no later than a stage called a morula. A morula is like a ball of cells, which are identical, so trophoblast have not yet distinguished themselves. Such twins end up each with its own placenta (as well as its own amniotic sac). It’s not the usual case with monozygotic twins, but it is the usual case with dizygotic twins.

Consequently, a common way that a pregnant woman finds out that she is carrying monozygotic twins is that ultrasonography reveals that they are sharing a placenta, even if they each have a private amniotic sac. This is important, because, in the handful of cases of  sesquizygotic twins, the story begins when ultrasound examination reveals two amniotic sacs and one placenta, suggesting monochorionic diamniotic twins, the typical identical twins. But then, something else happens. In one case, several years ago in Australia, ultrasound of the two babies showed that they shared a placenta, but that one was male and the other was female. In another case, the ultrasonography showed a monochorionic diamniotic twin pregnancy, and both babies were female, but the mother had light skin and the father dark skin, and the two, supposedly monozygotic twins did not match in skin color. One came out lighter and the other darker. Then we tested genetically, they proved to be about 75 percent identical.

As for how sesquizygotic twins could form in the first place and survive early pregnancy, embryologists are still working out the biology, but the idea being floated around is called dispermic fertilization. This means that two sperm cells get their nuclei inside the same ovum. But how could this be, since, as we have discussed, the fertilized ovum, called a zygote, must have the right number of chromosomes. Gametes (ova and sperm cells) are what biologists call haploid. They have half the genome —half the chromosomes, half the amount of DNA in the nucleus— as a somatic cell (body cell) has. While each of your body cells has 23 pair of chromosomes, or 46 chromosomes total, which is called a diploid genome, each gamete has just one set of 23 chromosomes. When an ovum is fertilized by a sperm cell, the haploid genome (23 chromosomes) and the haploid genome of the sperm (23 chromosomes) combine into a genome of 46 chromosomes in the zygote. But if a second sperm cell also fertilizes the same ovum, then the zygote, and all of the cells into which it divides, should be triploid, meaning having three sets of chromosomes for a total chromosome count of 69. Polyploidy —having multiple sets of chromosomes— is normal in plants, but it’s fatal in humans.

But what happens in sesquizygotic twins is that they end with diploid cells —46 chromosomes in each cell— but the genetic mixing is balanced more or less with the genetic contribution from the two sperm cells. Now this could be on account of a single ovum splitting into two ova clones prior to fertilization, leading to one sperm cell fertilizing one clone and the other sperm cell fertilizing the other clone. Alternatively, one sperm cell may divide into two clones when in the vicinity of two different ova, then one cloned sperm fertilizes each. This seems exquisitely unlikely, since hundreds of sperm cells must reach each ovum in order for one sperm to get its nucleus inside to begin fertilization.

On the other hand, there also is evidence that sesquizygotic twins each being a chimera, meaning that the cells of each individual do not all have the same genome. Chimerism is something that can happen with singleton babies, not just with twins. Depending on which tissues in the embryo get which type of cells, an embryo may develop normally, or may develop with problems. If an embryo is a chimera of male and female cells (some cells are XY, other cells are XX), for instance, if the chimerism is in tissues that give rise to reproductive tissues, the fetus and newborn could end up with ambiguous genitalia. This happed with a twin in one case that turned out to be a case of sesquizygotic twinning.

In any case, with scientists and people growing increasingly aware of this unusual twinning phenomenon, we could be headed into a time when certain sets of twins will want to get tested to see if they are more than dizygotic twins. One such example would be when a pair of twins appears extremely identical, despite being different sexes.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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