Identical twins develop from a single egg cell that divides into two embryos, but occasionally, one twin “vanishes” during development, leaving only one infant to be born. A recent study raises the possibility that your DNA could show if you were an identical twin in the womb, even if your sibling vanished before you were born.
The authors of a recent study published in Journal Nature Communications focused on so-called epigenetic alterations discovered in twin DNA. Epigenetic factors are those that have the ability to turn genes “on” or “off” without altering the DNA sequence underlying them. For instance, tiny chemicals known as methyl groups can adhere to particular genes like sticky notes and stop the cell from reading those genes, essentially switching it off.
The DNA of identical twins has a distinctive pattern of sticky methyl groups, according to the recent study. The researchers noted that this pattern, which spans 834 genes, can be utilized to distinguish identical twins from fraternal twins and non-twins. In fact, the scientists used these findings to construct a computer system that can accurately distinguish an identical twin based just on the distribution of methyl groups across their DNA.
The current study didn’t test this hypothesis, but in theory such a technology would also be able to identify someone who had a disappearing twin.
The genes covered in these methyl groups perform varied roles in cell formation, proliferation, and adhesion, which means they help cells attach to one another. In essence, this methyl group pattern is a kind of “molecular scar” left over from the early embryonic development of identical twins. The specific role that these methylation genes may have in the growth, development, or health of identical twins is unknown in light of the results of the current study.
The authors sought to gain a better understanding of why identical twinning happens in the first place by examining these early developmental scars. Scientists are aware that the zygote separates at a specific stage of development, but the reason why the splitting occasionally does place has remained a mystery. According to the study’s primary author, Jenny van Dongen, an assistant professor in the department of biological psychology at Vrije University (VU) Amsterdam, “[the study] was inspired by the fact that we understood very little about why monozygotic twins arise.”
According to a 1990 article in the International Journal of Fertility and Sterility, an estimated 12% of human pregnancies begin as multiple pregnancies, but less than 2% are carried to term, meaning the remainder result in a so-called vanishing twin. Fraternal twins are typically more prevalent than identical ones when both twins survive to term.
There is evidence that a mother’s likelihood of having fraternal twins, which occur when two eggs ovulate simultaneously, is influenced by genetics. For instance, research suggests that genes related to hyperovulation may be active and that fraternal twinning might occur in families, according to van Dongen. Comparatively, the global occurrence of identical twins, which occurs in around 3 to 4 out of every 1,000 births, suggests that genetics is not the primary cause of the phenomena. According to senior author Dorret Boomsma, a professor at the VU Amsterdam Department of Biological Psychology, “it’s really a mystery in developmental biology.”
Since methyl groups decorate a person’s DNA and are involved in the earliest stages of embryonic development, the team wondered if the answer to this puzzle might be stored in these molecules. The methyl groups that are added to our DNA during development are also copied down when our cells continue to divide, which allows them to persist into maturity, owing to specialized proteins called methyltransferases.
The team collected epigenetic information for the new study from six sizable twin cohorts, totaling more than 6,000 people. The cohorts included both identical twins and fraternal twins as well as some non-twin family members of these individuals. By including the fraternal twins, the team could check whether any epigenetic patterns seen in identical twins were actually unique to them and not common to all kinds of twins.
The majority of the DNA methylation data came from adult blood samples, however one data set included child cheek swab samples. Additionally, the team discovered consistent methylation patterns in identical twin DNA across all samples. According to van Dongen, “it appears that something occurs very early in development, and this remains inscribed in the methylation pattern of distinct cell types in our body.” It still exists in our cells as an archive. She said that it is currently unknown if the methylation pattern is a cause, effect, or outcome of identical twinning, or what precise impact these methyl groups have on gene expression (the “on” or “off” of a gene).
We definitely need functional investigations,” said van Dongen, referring to studies looking at how these changes influence actual cells, “to truly grasp the exact steps that take place early in embryonic development that contribute to the generation of monozygotic twins.” The team intends to carry out these investigations using animal models, human cells in lab pans, and maybe blastoids, which are models of the human embryo.
According to van Dongen, more research should make it possible to produce a genetic test that can tell if you’ve ever had a twin embryo. For example, if a woman had an identical twin embryo at some point during pregnancy, the current test would only be positive 70% of the time, so any businesses hoping to commercialize the study need to increase its accuracy, adds van Dongen. Furthermore, any test developed based on this research wouldn’t detect persons who had an embryonic twin that wasn’t identical.
Journal reference: Nature Communications, DOI: 10.1038/s41467-021-25583-7