Identical siblings are used to sharing a lot with their twin, including their DNA. But new research suggests all identical twins share a common signature of twinhood, not in their DNA, but on it.
This signature is part of the epigenome, chemical markers that dot many spots along DNA and influence the activity of genes without altering their sequence. Identical twins everywhere largely share a specific set of these marks that persists from birth to adulthood, researchers report September 28 in Nature Communications. These shared epigenetic tags could be used to identify people who were conceived as identical twins but lost their sibling in the womb or were separated at birth.
“This paper is absolutely fascinating,” says Nancy Segal, a developmental psychologist at California State University, Fullerton who has researched twins but wasn’t involved in the study. The research sets the groundwork for scientists to better understand “what might cause a fertilized egg to split and form monozygotic [identical] twins,” she says.
Despite humans’ age-old fascination with identical twins, the biological process that generates them, known as monozygotic twinning, “is an enigma,” says Jenny van Dongen, an epigeneticist at Vrije Universiteit Amsterdam.
Researchers know that identical twins form after a fertilized egg, called a zygote, somehow splits into two embryos during development. But why this cleavage happens remains unknown, van Dongen says. For the most part, identical twins don’t run in families, and they occur at roughly the same rate worldwide — about 3 to 4 per 1,000 births. With no clear genetic or environmental cause, the prevailing hypothesis is that identical twins arise at random, she says.
Early development, for twins and non-twins alike, happens amid a flurry of epigenetic changes that turn many genes on or off as an embryo takes shape. Some of these changes may account for slight differences between identical twins (SN: 7/17/12). So to better understand what makes a zygote split to form identical twins, “it makes sense to look at epigenetics,” van Dongen says.
She and colleagues looked for epigenetic differences at over 450,000 sites along the genomes of nearly 6,000 monozygotic twins and dizygotic, or fraternal, twins. Comparing identical twins with fraternal twins, as opposed to comparing twins to non-twins, allowed the researchers to rule out any epigenetic changes that stemmed from the unusual experience of sharing a womb.
At 834 spots along the genome, identical twins were strikingly similar, the researchers found. These shared epigenetic marks were concentrated in certain parts of the genome, including centromere and telomere regions on chromosomes. Some marks were near genes involved in early developmental processes, including those that regulate how tightly cells stick to one another. Whether these differences have health consequences for identical twins is unclear, van Dongen says.
These epigenetic signs popped up in twins young and old, from places as far-flung as Finland to Australia and were found in different cell types. The shared marks are so uniquely common to identical twins that the researchers were able to devise a test that can determine, with up to 80 percent accuracy, whether an individual is an identical twin. That includes individuals who don’t know that they lost their twin during pregnancy, a phenomenon known as vanishing twin syndrome, and twins who were separated at birth.
“This is a very, very important finding that opens up a lot of avenues of inquiry,” says Segal, the developmental psychologist. For example, identical twins are predisposed for a variety of conditions, from left-handedness to certain congenital disorders such as spina bifida, where the spine fails to develop properly. Perhaps, for some portion of people, these conditions stem from being an unknown identical twin, she says.
Whether this epigenetic signature is a cause, consequence or by-product of monozygotic twinning remains unclear, van Dongen says. It’s possible that some of these epigenetic changes tell a zygote to split. Alternatively, these chemical marks could reflect the epigenetic aftermath of the splitting event.
“They could be like a persistent molecular scar of the [splitting] process itself,” says Robert Waterland, an epigeneticist at Baylor College of Medicine in Houston. “An embryo splitting in two pieces would kind of upset things,” he says, and that could disrupt normal epigenetic processes in a way that leaves a permanent mark. He gravitates towards that molecular scar interpretation, though more studies are needed to know for sure, he says.
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