Am i a twin? Dna attachments reveal it

All identical twins carry a unique epigenetic signature on their genetic material

Identical twins carry an epigenetic signature throughout their lives, which they have in common with all other monozygotic twins. © BorupFoto/ Getty images

Surprising discovery: you can tell if someone is an identical twin by their epigenome – the appendages on their DNA. Because all monozygotic twins share a specific pattern of these epigenetic appendages. In contrast, fraternal twins or normal siblings do not have this signature, researchers report in the journal Nature Communications. This twin signature is detectable throughout life and could even be used to identify unidentified twins.

Monozygotic twins form when a fertilized egg divides shortly after conception. This results in two embryos that carry the same genetic material. Such monozygotic twins are in principle genetic clones, even though gene differences may accumulate during their development in the womb due to mutations. Unlike fraternal twins, however, the birth of identical twins does not run in the family. The common assumption is that the division of the zygote is therefore based on a coincidence.

View of the epigenome

Or not after all? A discovery by Jenny van Dongen of the Free University of Amsterdam and her colleagues now raises doubts about this. That’s because they have discovered an epigenetic signature that is found in all identical twins – across all kinship boundaries and test groups. This signature distinguishes monozygotic twins from dizygotic twins, but also from people with normal siblings or only children.

For their study, the team had studied the pattern of methyl attachments to the DNA of more than 4.000 identical and fraternal twins compared. "We deliberately chose fraternal twins as a comparison group because they also share the womb with their sibling," the researchers explain. Thus, the aligning influence of this "prenatal WG" can be separated from other effects. In addition, however, they also included a control group of non-twins.

DNA base cytosine with and without epigenetic methyl group (circle). © public domain

Markers at 834 sites

The analyses revealed something astonishing: There are 834 sites on the genome of identical twins that show a methylation that is typical only for this group. Approximately 60 percent of these sites have matching missing attachments, while the remaining 40 percent of sites have methyl attachments present in nearly all identical twins. Moreover, this twin signature can be detected in blood samples as well as in saliva or brain tissue, as van Dongen and her colleagues found.

"Thus, we show that monozygotic twins carry a robust and specific signature of DNA methylation in their body tissues," the researchers write. "This signature includes regions near telomeres as well as in the center of chromosomes and involves genes involved in cell adhesion, cell differentiation, and the WNT signaling pathway." The latter is considered crucial for embryonic development.

Signature remains detectable throughout life

To learn whether this twin signature remains stable throughout life, the team analyzed blood samples taken from twins every five years from birth into adulthood. The result: Although many epigenetic markers change during the course of life due to environmental influences and lifestyle, this was not the case with the twin signature: The methylations typical of monozygotic twins were preserved.

In principle, identical twins thus carry a molecular marker of their split origin throughout their lives. "This is a really big discovery," says senior author Dorret Boomsma of the Free University of Amsterdam. "It is the first time we have found a biological marker of this phenomenon in humans. This astonishing finding gives us completely new insights into the background of monozygotic twin formation."

Clues to the cause of twinning

It is known from previous studies that embryos undergo multiple waves of DNA methylation shortly after conception. Some take place before the differentiation of the cells, others only afterwards. According to the researchers, the detection of the twin signature in different cells and tissues indicates that these markers must have their origin very early in embryonic development.

"It seems that something happens very early in development that is then maintained in the methylation pattern of all different types of cells in our body, " says van Dongen. But exactly when and how this specific epigenome signature arises is unknown for now. The team hopes to learn more about this when they study in more detail which genes are affected by the methylation pattern and in what ways.

"Vanishing Twin" syndrome

But the twin signature that has now been discovered could also open up completely new diagnostic possibilities: "Because identical twins retain this molecular signature throughout their lives, we could find out in retrospect whether a person was originally part of a monozygotic twin pair," van Dongen and her colleagues explain. You could identify someone as a twin even if the sibling is missing or died in the womb and was reabsorbed.

This could also provide more information about the so-called "vanishing twin" syndrome. Because although about twelve percent of all pregnancies begin as multiples, only two percent of these multiples are carried to term. Identical twins in particular have a greatly increased risk of malformations and prenatal complications, as the scientists report. As more becomes known about the causes and origins of monozygotic twins, this could also shed light on some unanswered questions here. (Nature Communications, 2021; doi: 10.1038/s41467-021-25583-7)

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